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This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.
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Masculino , Humanos , Epididimo , Transtorno 46,XY do Desenvolvimento Sexual/genética , Transtornos do Desenvolvimento Sexual , Mutação , Mutação de Sentido Incorreto , Fator Esteroidogênico 1/genéticaRESUMO
Objective:To investigate the clinical values of progastrin-releasing peptide (Pro-GRP), neuron-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), squamous cell carcinoma antigen (SCCA) and human human epididymis protein 4 (HE4) detections in the diagnosis of lung cancer patients.Methods:The clinical data of 200 lung cancer patients who were admitted to the Second Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2021 were retrospectively analyzed. According to the pathological type, the patients were divided into lung adenocarcinoma group (80 cases), lung squamous cell carcinoma group (75 cases) and small cell lung cancer group (45 cases). Fifty patients with benign lung diseases and 50 healthy physical examiners who were admitted to the hospital during the same period were selected. All the subjects were tested for the levels of Pro-GRP, NSE, CYFRA21-1, SCCA and HE4, and the differences of each index level in the subjects of different subgroups were compared. The receiver operating characteristic (ROC) curve was drawn, and using pathological diagnosis result as the gold standard, the diagnostic efficacy of each index alone and in combination for lung cancer was compared.Results:The serum levels of Pro-GRP, NSE, CYFRA21-1, SCCA and HE4 in lung cancer group were higher than those in the benign lung diseases group and the healthy control group (all P < 0.001). There were no statistical differences in the levels of serum Pro-GRP, NSE, CYFRA21-1, SCCA and HE4 between the benign lung diseases group and the healthy control group (all P > 0.05). The levels of Pro-GRP, NSE and HE4 in the small cell lung cancer group were higher than those in the lung adenocarcinoma group and the lung squamous cell carcinoma group (all P < 0.05). NSE and HE4 levels in the lung adenocarcinoma group were higher than those in the lung squamous carcinoma group (both P < 0.05), while CYFRA21-1 and SCCA levels were lower than those in the lung squamous carcinoma group (both P < 0.05). The AUC of lung cancer diagnosed by HE4 was the largest (0.813), the AUC of lung adenocarcinoma diagnosed by HE4 was the largest (0.824), the AUC of lung squamous carcinoma diagnosed by CYFRA21-1 was the largest (0.884), and the AUC of small cell lung cancer diagnosed by NSE was the largest (0.959). The AUC of lung cancer diagnosed by combined detection of 5 indicators was 0.951, the AUC of lung adenocarcinoma and small cell lung cancer diagnosed by combined detection of 5 indicators was 0.975 and 0.996, and the AUC of lung squamous cell carcinoma diagnosed by combined detection of CYFRA21-1, SCCA and HE4 was 0.967. Conclusions:The levels of Pro-GRP, NSE, CYFRA21-1, SCCA, HE4 and other indicators have certain clinical values in the diagnosis of lung cancer and its pathological types, and the combined detection of each index is more valuable than a single index.
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Objective:To investigate the diagnostic values of human epididymis protein 4 (HE4), endothelial cell specific molecule-1 (ESM-1) and epidermal growth factor receptor (EGFR) for lung cancer.Methods:The clinical data of 90 patients with lung cancer and 50 patients with benign lung diseases diagnosed by the pathological examination in Tangshan People's Hospital from December 2019 to January 2021 were retrospectively analyzed, and 40 healthy physical examiners in the same period were selected as the controls. The serum HE4 levels were detected by electrochemiluminescence method. The serum ESM-1 and EGFR levels were tested by enzyme-linked immunosorbent assay. The differences in serum HE4, ESM-1 and EGFR levels between the three groups were compared; logistic regression analysis was used to screen out the effective indicators for the diagnosis of lung cancer and to construct a prediction model for the diagnosis of lung cancer. Using pathological diagnosis result as the gold standard, the receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of indicators for lung cancer was evaluated.Results:The levels of serum HE4 in lung cancer group, benign lung diseases group and healthy control group were 119.55 pmol/L (82.06 pmol/L, 189.00 pmol/L), 58.84 pmol/L (45.62 pmol/L, 69.41 pmol/L) and 42.67 pmol/L (37.09 pmol/L, 51.84 pmol/L), the levels of ESM-1 were 33.00 ng/ml (25.85 ng/ml, 47.40 ng/ml), 20.14 ng/ml (11.93 ng/ml, 28.90 ng/ml) and 15.39 ng/ml (11.84 ng/ml, 20.19 ng/ml), and the levels of EGFR were 46.60 pg/ml (37.45 pg/ml, 58.98 pg/ml), 32.77 pg/ml (26.27 pg/ml, 40.86 pg/ml) and 30.43 pg/ml (27.54 pg/ml, 35.75 pg/ml), and the differences in each indicator among the three groups were statistically significant (all P < 0.001). The levels of serum HE4, ESM-1 and EGFR in lung cancer group were higher than those in benign lung diseases group and healthy control group. In patients with lung cancer, logistic regression analysis was performed with HE4 (X 1), ESM-1 (X 2) and EGFR (X 3) as the independent variables and pathological diagnosis as the dependent variable, and a lung cancer prediction regression model was established: P = 0.171X 1+0.351X 2+0.184X 3-24.660. The accuracy of this model in predicting lung cancer could reach 98.5%, and serum HE4, ESM-1 and EGFR were risk factors for the occurrence of lung cancer (all P < 0.05). The area under ROC curve from high to low was HE4 (0.960), ESM-1 (0.942) and EGFR (0.859). The diagnostic sensitivity of serum HE4 63.67 pmol/L for lung cancer was 86.7%, and the specificity was 97.5%. Both serum HE4 ( r = 0.304, P = 0.004) and ESM-1 ( r = 0.416, P < 0.001) were correlated with EGFR. Conclusions:Serum HE4, ESM-1 and EGFR can be used as effective indicators for the diagnosis of lung cancer, and the prediction model established based on the three serum tumor markers is of good value for the diagnosis and prediction of lung cancer.
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Objective To compare the clinical significance of human epididymis protein 4(HE4),CA125, ROMA in the differential diagnosis of ovarian cancer.Methods From May 2016 to October 2017,240 patients with ovarian tumor in Xuzhou Cancer Hospital were selected .According to the result of postoperative pathology ,the patients were divided into benign ovarian disease group ( n =120 ) and ovarian cancer group ( n =120 ) .And 100 healthy women from medical examination center were selected as control group .The electrochemiluminescence ( ECLIA ) technique was used to assess the serum levels of CA 125,HE4,and ROMA was calculated .The clinical significance of HE4,CA125,ROMA in the differential diagnosis of ovarian cancer was analyzed by statistic methods .Results The CA125,HE4 concentrations and ROMA in the ovarian cancer group [(370.9 ±213.2) U/mL,(364.4 ±227.0) pmpl/L, (80.2 ±26.1)％] were higher than those in the benign ovarian disease group and the health control group ( all P<0.01),there were no statistically significant differences between the benign ovarian disease group and the healthy control group(P=0.356,P=0.321,P=0.292).The sensitivity,specificity,positive and negative predictive values , accuracy of ROMA were higher than those of HE 4 and CA125.By using the ROC analysis ,the AUC for CA125,HE4, ROMA were 0.832,0.888,0.960,respectively,AUC(CA125) <AUC(HE4) <AUC(ROMA).Conclusion CA125 and HE4 have important value in the diagnosis of ovarian cancer ,but the ROMA shows the best diagnostic performance and actual value .
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Objective@#To compare the clinical significance of human epididymis protein 4(HE4), CA125, ROMA in the differential diagnosis of ovarian cancer.@*Methods@#From May 2016 to October 2017, 240 patients with ovarian tumor in Xuzhou Cancer Hospital were selected.According to the result of postoperative pathology, the patients were divided into benign ovarian disease group(n=120) and ovarian cancer group(n=120). And 100 healthy women from medical examination center were selected as control group.The electrochemiluminescence (ECLIA) technique was used to assess the serum levels of CA125, HE4, and ROMA was calculated.The clinical significance of HE4, CA125, ROMA in the differential diagnosis of ovarian cancer was analyzed by statistic methods.@*Results@#The CA125, HE4 concentrations and ROMA in the ovarian cancer group[(370.9±213.2)U/mL, (364.4±227.0)pmpl/L, (80.2±26.1)%]were higher than those in the benign ovarian disease group and the health control group(all P<0.01), there were no statistically significant differences between the benign ovarian disease group and the healthy control group(P=0.356, P=0.321, P=0.292). The sensitivity, specificity, positive and negative predictive values, accuracy of ROMA were higher than those of HE4 and CA125.By using the ROC analysis, the AUC for CA125, HE4, ROMA were 0.832, 0.888, 0.960, respectively, AUC(CA125)<AUC(HE4)<AUC(ROMA).@*Conclusion@#CA125 and HE4 have important value in the diagnosis of ovarian cancer, but the ROMA shows the best diagnostic performance and actual value.
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BACKGROUND: Tumor markers are useful for detection and preoperative evaluation of ovarian tumors. We evaluated the clinical usefulness of cancer antigen (CA) 125, human epididymis 4 (HE4), and CA72-4 levels and Risk of Ovarian Malignancy Algorithm (ROMA) values for differential diagnosis of malignant and borderline tumors among suspected ovarian tumors, and the effects of endometriosis on these tumor markers. METHODS: In a total of 266 patients (213, 14, and 39 with benign, borderline and malignant tumors, respectively), CA125, HE4, and CA72-4 levels were measured, and ROMA values were calculated. Medians of each marker were compared among the three groups. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to analyze the diagnostic performance of each marker. RESULTS: All markers were significantly higher in the malignant group than in the benign group. HE4 levels and ROMA values were significantly higher in the malignant group than in the borderline group. ROMA value had the highest AUC for distinguishing the malignant and borderline groups from the benign group in premenopausal (0.773) and postmenopausal (0.927) patients. CA125 level was significantly higher in patients with endometriosis than in those without (P<0.001), whereas HE4 and CA72-4 levels were not affected by endometriosis (P=0.128 and 0.271, respectively). CONCLUSIONS: ROMA value is the best marker to distinguish malignant and borderline tumors from benign tumors in pre- and postmenopausal patients. HE4 and CA72-4 levels provide information on possible CA125 elevation due to endometriosis.
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Feminino , Humanos , Masculino , Área Sob a Curva , Biomarcadores Tumorais , Diagnóstico Diferencial , Endometriose , Epididimo , Curva ROC , Cidade de Roma , Sensibilidade e EspecificidadeRESUMO
Background: Ovarian malignancies has the highest mortality rate among all gynaecological malignancies. Surface epithelial tumors form two thirds of all ovarian neoplasm and 90% of all ovarian cancers are surface epithelial carcinomas. Mortality in case of ovarian malignancy is high due to late diagnosis. Early and accurate diagnosis can improve the case specific management. HE4 (Human Epididymis Protein 4) which is proved to be overexpressed in the ovarian cancer cells, is considered a new biomarker for ovarian cancer diagnosis which helps in early diagnosis and patient management. Aims and objectives of the study was to evaluate the immunohistochemical expression of HE4 in various ovarian malignancies.Methods: It was a cross sectional, prospective, single institution-based study, conducted in the department of Pathology in collaboration with the Department of Gynaecology and Obstetrics, from December 2016 to January 2019 in institution. A total 74 ovarian malignancies were selected for this study.Results: Serous carcinoma was the most common ovarian malignancy followed by endometrioid carcinoma. Highest percentage of expression of HE4 was seen in high grade serous cancer and malignant endometrioid tumor.Conclusions: HE4 was highly expressed in malignant ovarian tumour especially serous and endometrioid carcinoma and can be used as an important biomarker for malignant ovarian neoplasm. Expression in high grade ovarian serous cancer support its prognostic value also.
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Objective To explore the diagnostic value of combined detection of serum human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) for ovarian epithelial cancer. Methods Patients who underwent surgery for the adnexal tumor at Shanxi Provincial Cancer Hospital from January 2012 to December 2017 were enrolled. According to the postoperative pathological results, these patients were divided into the ovarian epithelial cancer group (494 cases) and benign ovarian disease group (462 cases). The serum expressions of HE4 and CA125 in the two groups were detected by enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay. The diagnostic value of detection of HE4 and CA125 alone or in combination for ovarian epithelial cancer was analyzed. Results The median levels (P 25-P 75) of serum CA125 and HE4 in ovarian epithelial cancer group were 273.34 U/ml (39.34 U/ml, 709.74 U/ml) and 199.08 pmol/L (75.81 pmol/L, 449.20 pmol/L), which were higher than those in ovarian benign disease group [16.30 U/ml (6.30 U/ml, 53.60 U/ml) and 39.54 pmol/L (29.57 pmol/L, 53.80 pmol/L)] (both P< 0.05). There was a positive correlation between serum CA125 and HE4 levels in ovarian epithelial cancer group (r=0.481, P<0.01). Serum CA125 and HE4 levels in patients with stage Ⅲ and Ⅳ were higher than those in patients with stageⅠand Ⅱ (both P<0.05), and serum CA125 and HE4 levels in patients with poor differentiation were higher than those in patients with moderate differentiation (P< 0.05). Compared with CA125, the specificity and positive predictive value of serum HE4 for the diagnosis of ovarian epithelial cancer were higher (both P< 0.01). Compared with HE4 alone, the sensitivity of CA125 combined with HE4 increased (P= 0.004) and the specificity decreased (P= 0.044). When both CA125 and HE4 were positive for positive results, compared with HE4 alone, the specificity and positive predictive value increased (both P< 0.01), but the sensitivity decreased (both P< 0.01). In patients with CA125+ HE4-, the sensitivity and specificity decreased, while in CA125-HE4+patients, the specificity was elevated, but the difference was not statistically significant (P= 0.892). When one of CA125 and HE4 was positive for positive results, the sensitivity and negative predictive value increased (both P<0.01), but the specificity and positive predictive value decreased (both P<0.01). The area under the curve of serum CA125 and HE4 combined detection was 0.911, indicating its clinical diagnostic value was better than that of the two alone. Conclusions In the diagnosis of epithelial ovarian cancer, the specificity of serum HE4 is higher than that of CA125, but the sensitivity is lower than that of CA125. The combined detection of HE4 and CA125 is more conducive to improve the diagnostic accuracy of ovarian epithelial cancer.
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BACKGROUND: External quality assessment (EQA) is important for standardizing cancer biomarker assays, thereby, ensuring accurate and precise results. Although the human epididymis-specific protein 4 (HE4) assay has been increasingly used to detect and monitor ovarian malignancy in Korea, a nation-wide EQA program for HE4 has not been appropriately established. To conduct an EQA program, a large amount of quality control (QC) materials are required. This study aimed to produce HE4 QC materials for an EQA program and evaluate their homogeneity and stability. METHODS: QC materials for three different concentrations of HE4 were produced from the collected remnant sera of 275 patients for whom the HE4 assays were performed. These materials were evaluated for homogeneity between vials and stability during storage. The frozen QC materials were distributed to 13 representative organizations for a provisional EQA. RESULTS: The total coefficient of variation of the HE4 QC materials of three concentrations was 0.75%–1.24%, and no significant differences were noted between vials; therefore, the samples were considered to be homogenous. With respect to stability, the HE4 QC materials were found to be stable till 30 days when frozen and for 24 hours when refrigerated. The results of the provisional HE4 EQA were reviewed and the survey results were reported to each participant. CONCLUSIONS: The HE4 QC materials produced from remnant specimens were found to be homogenous between vials and stable in a frozen condition until 30 days. The findings of this study may be practically applied for establishing a future HE4 EQA program.
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Humanos , Masculino , Epididimo , Coreia (Geográfico) , Neoplasias Ovarianas , Controle de QualidadeRESUMO
Objective@#To explore the diagnostic value of combined detection of serum human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) for ovarian epithelial cancer.@*Methods@#Patients who underwent surgery for the adnexal tumor at Shanxi Provincial Cancer Hospital from January 2012 to December 2017 were enrolled. According to the postoperative pathological results, these patients were divided into the ovarian epithelial cancer group (494 cases) and benign ovarian disease group (462 cases). The serum expressions of HE4 and CA125 in the two groups were detected by enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay. The diagnostic value of detection of HE4 and CA125 alone or in combination for ovarian epithelial cancer was analyzed.@*Results@#The median levels (P 25 - P 75) of serum CA125 and HE4 in ovarian epithelial cancer group were 273.34 U/ml (39.34 U/ml, 709.74 U/ml) and 199.08 pmol/L (75.81 pmol/L, 449.20 pmol/L), which were higher than those in ovarian benign disease group [16.30 U/ml (6.30 U/ml, 53.60 U/ml) and 39.54 pmol/L (29.57 pmol/L, 53.80 pmol/L)] (both P < 0.05). There was a positive correlation between serum CA125 and HE4 levels in ovarian epithelial cancer group (r = 0.481, P < 0.01). Serum CA125 and HE4 levels in patients with stage Ⅲ and Ⅳ were higher than those in patients with stage Ⅰ and Ⅱ (both P < 0.05), and serum CA125 and HE4 levels in patients with poor differentiation were higher than those in patients with moderate differentiation (P < 0.05). Compared with CA125, the specificity and positive predictive value of serum HE4 for the diagnosis of ovarian epithelial cancer were higher (both P < 0.01). Compared with HE4 alone, the sensitivity of CA125 combined with HE4 increased (P = 0.004) and the specificity decreased (P = 0.044). When both CA125 and HE4 were positive for positive results, compared with HE4 alone, the specificity and positive predictive value increased (both P < 0.01), but the sensitivity decreased (both P < 0.01). In patients with CA125+ HE4-, the sensitivity and specificity decreased, while in CA125- HE4+ patients, the specificity was elevated, but the difference was not statistically significant (P = 0.892). When one of CA125 and HE4 was positive for positive results, the sensitivity and negative predictive value increased (both P < 0.01), but the specificity and positive predictive value decreased (both P < 0.01). The area under the curve of serum CA125 and HE4 combined detection was 0.911, indicating its clinical diagnostic value was better than that of the two alone.@*Conclusions@#In the diagnosis of epithelial ovarian cancer, the specificity of serum HE4 is higher than that of CA125, but the sensitivity is lower than that of CA125. The combined detection of HE4 and CA125 is more conducive to improve the diagnostic accuracy of ovarian epithelial cancer.
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Epithelial ovarian cancer (EOC) has the highest mortality rate among the gynecological malignancies. Because of its early symptoms are not obvious and lack of effective screening methods, more than 70％ patients have been diagnosed at late stage (stage Ⅲ-Ⅳ). Although the 5-year progression-free survival (PFS) of EOC was prolonged with the improvement of treatment methods, its prognosis was still poor, and 50％-95％ patients relapsed within 2 years after treatment. Human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) are widely used in the evaluation of diagnosis, treatment efficacy and prognosis of EOC, but the evaluation effect of both HE4 and CA125 is rarely reported. Therefore, it is necessary to summarize the research progress of HE4 and CA125 in evaluating the diagnosis, treatment efficacy and prognosis of EOC.
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Objective: To investigate the value of risk ovarian malignancy algorithm (ROMA) in evaluation of the risk of epithelial ovarian cancer and its association with the clinical pathological stages, and to provide a basis for the clinical diagnosis and treatment and prognosis analysis of epithelial ovarian cancer.Methods: The clinical materials of 135 patients with ovarian tumor confirmed by paraffin section pathology after operation were retrospectively analyzed. The patients were divided into benign ovarian tumor group(n=66), epithelial ovarian cancer group(n=58) and non-epithelial ovarian cancer group(n=11).According to the cutoff values of HE4,CA125,and ROMA of the patients in various groups,the positive rates of HE4,CA125,and ROMA of the patients in various groups were calculated.Based on the serum levels of human epididymis protein 4(HE4) and carbohydrate antigen 125(CA125) detected before operation of the patients in various groups, the relationships between the positive rates of serum HE4, CA125 and ROMA and the clinical stages of the patients with ovarian cancer;their diagnosis efficacies in the patients with ovarian cancer were evaluated. Results: The serum CA125, HE4 levels and ROMA value of the patients in epithelial ovarian cancer group were significantly higher than those in benign ovarian tumor group and non-epithelial ovarian cancer group (P0.05). Among the three indexes, ROMA had the highest diagnostic efficacy index and CA125 had the lowest.Conclusion: The diagnostic value of ROMA for evaluating the risk of epithelial ovarian cancer was higher than those of CA125 and HE4, which has a better diagnostic value for the postmenopausal patients and can improve the early diagnosis efficiency of ovarian cancer.
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OBJECTIVE@#To compare the performance of serum cancer antigen 125 (CA125), human epididymis protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA) and Copenhagen index (CPH-I) for differential diagnosis of benign and malignant diseases in patients with ovarian mass.@*METHODS@#We retrospectively analyzed the data of 719 women with pelvic mass, and the performance of preoperative serum levels of CA125 and HE4, ROMA and CPH-I for differential diagnosis of the masses was compared.@*RESULTS@#Of the 710 women analyzed, 531 were diagnosed with benign ovarian lesions, 44 with borderline ovarian tumors (BOTs), 119 with epithelial ovarian cancers (EOCs), and 25 with non-EOCs. In differentiating ovarian cancer (OC) and BOT from benign lesions, the area under the receiver-operator characteristic (ROC) curve (AUC) was 0.854 for HE4, 0.856 for ROMA, 0.854 for CPH-I, and 0.792 for CA125, demonstrating better diagnostic performance of HE4, ROMA, and CPH-I than CA125 alone; the diagnostic sensitivity was 56.9% for HE4, 70.2% for CA125, 69.1% for ROMA, and 63.8% for CPH-I; the specificity was the best with HE4 (94.4%) and CPH-I (94.7%). In sub-analysis of EOC benign lesions, the AUCs of HE4, ROMA, and CPH-I increased to 0.946, 0.947, and 0.943, respectively, all greater than that of CA125 (0.888). In other sub-analyses, HE4, ROMA, and CPH-I all showed greater AUCs than CA125 alone.@*CONCLUSIONS@#This study confirms the accuracy of HE4, ROMA, and CPH-I for differentiating malignant from benign ovarian mass, and all these 3 tests show better performance than CA125. Furthermore, HE4 and CPH-I is superior to ROMA and CA125 in terms of specificity, while CA125 and ROMA have better diagnostic sensitivities.
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Feminino , Humanos , Algoritmos , Biomarcadores Tumorais , Antígeno Ca-125 , Carcinoma Epitelial do Ovário , Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Proteínas , Estudos Retrospectivos , Proteína 2 do Domínio Central WAP de Quatro DissulfetosRESUMO
Objective To observe the expression of human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) in endometrial carcinoma(EC) tissues,and to explore the relationship between the expression of HE4 and CA125 and the occurrence and development of EC.Methods The EC and paracancerous tissue specimens of 35 EC patients were selected from December 2015 to December 2016 in the First People's Hospital of Yibin City.The expression of HE4 and CA125 in EC tissues and paracancerous tissues was detected by immunohistochemistry.The relationship between the expression of HE4,CA125 and the clinicopathological features of EC was analyzed;and the correlation between HE4 and CA125 was analyzed too.Results The positive expression rates of HE4 and CA125 in EC tissues were 82.9％ (29/35) and 74.3％ (26/35);they were 11.4％ (4/35) and 14.3％ (5/35) in paracancerous tissues respectively;the positive expression rates of HE4and CA125 in EC tissues were significantly higher than those in paracancerous tissues(x2 =35.831,25.533;P ＜0.05).The positive expression rates of HE4 and CA125 in stage Ⅲ and Ⅳ EC tissues were 100.0％ (20/20) and 90.0％ (18/20);they were 60.0％ (9/15) and 53.3％ (8/15) in stage Ⅰ and Ⅱ EC tissues respectively;the positive expression rates of HE4 and CA125 in stage Ⅲ and Ⅳ EC tissues were significantly higher than those in stage Ⅰ and Ⅱ EC tissues(x2 =9.655,4.266;P ＜ 0.05).The positive expression rates of HE4 and CA125 in medium and low differentiated EC tissues were 100.0％ (18/18) and 83.3％ (15/18);they were 64.7％ (11/17) and 64.7％ (11/17) in highly differentiated EC tissues respectively;the positive expression rates of HE4 and CA125 in medium and low differentiated EC tissues were significantly higher than those in highly differentiated EC tissues(x2 =7.667,4.137;P ＜0.05).The positive expression rates of HE4 and CA125 in EC tissues with myometrial invasion depth≥ 1/2 were 100.0％ (18/18) and 94.4％ (17/18);they were 64.7％ (11/17) and 52.9％(9/17) in EC tissues with myometrial invasion depth ＜ 1/2 respectively;the positive expression rates of HE4 and CA125 in EC tissues with myometrial invasion depth ≥ 1/2 were significandy higher than those in EC tissues with myometrial invasion depth ＜ 1/2(x2 =7.667,7.884;P ＜ 0.05).The positive expression rates of HE4 and CA125 in EC tissues with lymph node metastasis were 100.0％ (19/19) and 78.9％ (15/19);they were 62.5％ (10/16) and 68.8％ (11/16) in EC tissues without lymph node metastasis respectively;the positive expression rate of HE4 in EC tissues with lymph node metastasis was significantly higher than that in EC tissues without lymph node metastasis (x2 =8.599,P ＜ 0.05),but there was no significant difference in the positive expression rate of CA125 in EC tissues with lymph node metastasis and without lymph node metastasis (x2 =0.473,P ＜0.05).The expression of HE4 and CA125 in EC tissues was not related to age,tumor size and pathological type(P ＜ 0.05).The expression of HE4 in EC tissues was positively correlated with the expression of CA125 (r =0.608,P ＜0.05).Conclusion HE4 and CA125 may be involved in the development and development of EC.The expression of HE4 and CA125 is high in EC tissues,the expression level of them is closely related to clinical stage,histological differentiation and myometrial invasion depth of EC.The high expression of HE4 was also related to lymph node metastasis.
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Objective To study the value of serum human epididymal protein 4 (HE4) ,cytokeratin 19 frag-ment (CYFRA21-1) ,neuron-specific enolase (NES) and gastrin release precursors (Pro-GRP) in the diagnosis of female lung cancer .Methods A total of 100 cases of female lung cancer patients in the hospital were select-ed as the research object ,100 cases of benign lung diseases and 100 female health examiners as the control ,the serum levels of HE4 ,CYFRA21-1 ,NES and Pro-GRP were measured ,and the related statistical analysis was carried out .Results The serum levels of HE4 ,CYFRA21-1 ,NES and Pro-GRP in patients with lung cancer were significantly higher than those of benign lung disease and healthy control group (P<0 .05) ,and there was no significant difference between the benign lung disease group and the healthy control group (P>0 .05) . There was no significant difference in serum HE4 expression in different stages and pathological types of lung cancer (P>0 .05) .The ROC curve analysis showed that the area (AUC) of HE4 ,CYFRA21-1 and NES/Pro-GRP w ere 0 .927 ,0 .758 ,0 .652 and 0 .799 respectively ,and the best critical values w ere 63 .38 ,2 .05 ,14 .05 and 58 .50 respectively ,and the sensitivity was 88 .0％ ,80 .0％ ,60 .0％ ,71 .0％ respectively ,and the speci-ficity was 96 .0％ ,73 .0％ ,87 .0％ and 89 .0％ respectively .HE4 was obviously better than the other 3 items . Combined detection of HE4 ,CYFRA21-1 ,NES and Pro-GRP could also improve the diagnostic sensitivity of lung cancer ,which was 89 .0％ ,but the specificity had decreased by 88 .0％ .Conclusion The level of serum HE4 in female patients with lung cancer is significantly higher ,which can be used as a candidate marker for differential diagnosis of pulmonary benign and malignant diseases .The combined detection of these 4 markers has a high sensitivity for the diagnosis of female lung cancer ,which is suitable for the survey of female lung cancer in clinical .
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Objective To investigate the clinical value of serum human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125) combined with risk of ovarian malignancy algorithm (ROMA) index in the diagnosis of ovarian cancer. Methods A total of 541 patients in the Department of Gynaecology in Baoji Central Hospital from August 2016 to February 2018 were collected. The serum HE4 and CA125 levels were measured by using electrochemiluminescence immunoassay in 226 cases of ovarian cancer (ovarian cancer group), 315 cases of ovarian benign disease (ovarian benign disease group) and 100 female healthy people (the control group). ROMA index was calculated according to ROMA model and the results were analyzed statistically. Results The levels of serum HE4, CA125 and ROMA index were significantly different in premenopausal and postmenopausal ovarian cancer group, ovarian benign disease group and the control group (all P<0.05). The sensitivity and Yonden's index of the three combined diagnosis of serum HE4, CA125 and ROMA for premenopausal ovarian cancer were 97.01 ％ and 77.01 ％ respectively, which were higher than those of a single detection (HE4:79.37％, 69.11％;CA125:76.06％, 66.38％;ROMA index:89.55％, 72.41％;χ2sensitivity=12.35, P=0.000;χ2Yonden's index=6.460, P=0.013. The sensitivity and Yonden's index ofthe three combined diagnosis of serum HE4, CA125 and ROMA for postmenopausal ovarian cancer were 98.99 ％ and 82.99 ％ respectively, which were higher than those of a single detection (HE4: 86.90 ％, 79.40 ％; CA125: 82.98 ％, 76.31 ％; ROMA index: 93.54 ％, 80.64 ％; χ2sensitivity = 14.25, P = 0.000;χ2Yonden's index= 4.822, P= 0.031). The area under the curve of the combined detection of three indicators was higher than that of a single detection (premenopausal group: 0.871 vs. 0.682, 0.626, 0.708; postmenopausal group: 0.981 vs. 0.724, 0.705, 0.833), and there were significant differences (premenopausal group: χ2 =11.24, P= 0.000; postmenopausal group: χ2= 16.38, P= 0.000). Conclusion The combined detection of serum HE4, CA125 and ROMA index can increase the sensitivity and accuracy for diagnosing ovarian cancer, which can provide a more reliable basis for diagnosis and screening of ovarian cancer.
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Objective To explore the clinical effect of neoadjuvant chemotherapy combined with tumor cell subtraction in the treatment of advanced epithelial ovarian cancer,as well as the effects on serum epididymal secretory protein 4 ( Human Epididymis protein 4,HE4) ,and glucose polypeptide antigen 125 ( cancer antigen 125,CA125 ) . Methods From January 2010 to January 2014, patients with advanced ovarian cancer from Quanzhou First Hospital Affiliated to Fujian Medical University were selected. According to the difference of clinical treatment plan,128 patients with advanced epithelial ovarian cancer were divided into the observation group ( 68 cases ) and the control group ( 60 cases ) . The patients in the observation group were given neoadjuvant chemotherapy combined with tumor cytoreductivesurgery, and the control group was treated with tumor cytoreductivesurgery and conventional chemotherapy. The clinical efficacy, operation time, blood loss volume, ascites volume, complication, hospitalization time, HE4and CA125 were compared between the two groups. Also 1 year,3 year survival rate,HE4 and CA125 levels of the two groups were analyzed. Results The number of satisfactory tumor reduction cases in observation group was significantly higher than that in control group( 73. 53％( 50/68) ,51. 67％( 31/60) ,χ2=6. 56,P<0. 05) . The short-term effect of observation group was significantly better than that in control group( Z=5. 79,P<0. 05) . The operation time,blood loss volume,ascites volume,complication and hospitalization time of observation group were significantly lower than those in control group (operation time:(119. 6±39. 1) min vs. (177. 3±45. 6) min,t=7. 71,P<0. 05;blood loss:(378. 9 ±88.4) ml vs. (616.3±110.8) ml,t=13.47,P<0.05;ascites volume:(678.5±205.1) ml vs. (1372.4 ±405. 8) ml,t=12. 42, P<0. 05;complication: 13. 2％( 9/68) vs. 31. 7％( 19/60),χ2 = 6. 34, P<0. 05;hospitalization time:(10. 4±3. 2)d vs. (15. 3±3. 1)d,t=8. 77,P<0. 05). There was no significant difference in HE4 and CA125 between the two groups before treatment ( P>0. 05) . After chemotherapy,the level of HE4 and CA125 decreased significantly in the two groups after chemotherapy,and the observation group was significantly lower than the control group (HE4: (98. 3±28. 9) pmol/L vs. (153. 2±44. 1) pmol/L,t=8. 42,P<0. 05;CA125:(35. 3±14. 8) vs. (48. 3±14. 2) ) kU/L,t=5. 05,P<0. 05). The myelosuppression and digestive tract reaction in the observation group were more serious than those in control group (χ2=4. 09,4. 87,P<0. 05) . There was no significant difference in the 1 year survival rate between the two groups ( 86. 76％ vs. 81. 67％,χ2=0. 63, P>0. 05 ) . After 1 years of follow-up, the levels of HE4 and CAl25 in the observation group were significantly lower than those in the control group (HE4:(112. 2±33. 7) pmol/L vs. (189. 4±39. 6) pmol/L,t=10. 95,P<0. 05;CA125:(51. 2±14. 2) kU/L vs. (59. 7±18. 6) kU/L,t=2. 69,P<0. 05). 3 year survival rate in observation group was significantly higher than that in control group ( 55. 88％ vs. 38. 33％,χ2 =3. 94, P<0. 05). The levels of HE4 and CAl25 were significantly lower than those in control group(HE4:(166. 5±45. 5) pmol/L vs. (245. 7±51. 8) pmol/L,t=6. 25,P<0. 05;CA125:(77. 4±18. 5) kU/L vs. (94. 4±16. 7) kU/L,t=3. 61,P<0. 05) . Conclusion Neoadjuvant chemotherapy combined with cytoreductive surgery can effectively improve the clinical efficiency and improve the prognosis of patients with advanced epithelial ovarian cancer.
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Objective To investigate the expression of human epididymal protein 4 ( HE4) and its effect on prognosis in patients with epithelial ovarian cancer (EOC). Methods From 2009 to 2014,ninety-eight cases of epithelial ovarian cancer (EOC group) and 29 cases of benign ovarian tumor (benign group) and 100 healthy subjects (control group) were selected as research subjects. The serum HE4 was detected by double antibody sandwich enzyme-linked immunosorbent assay (ELISA),and the positive expression was determined by HE4＞150 pmol/L in serum. The concentration and positive rate of serum HE4 were compared among the three groups. The median serum HE4 level of EOC patients before treatment was divided into high level HE4 group and low level HE4 group. The median survival time of the two groups of EOC patients was compared. Results The median value of serum HE4 concentration (four percentile) in EOC group was 421. 8 (68. 7 ～ 2173. 9) pmol/L,47. 8 (35. 24 ～ 68. 5) pmol/L in the benign group and 43. 8 ( 32. 91 ～ 70. 4) pmol/ L in the control group. The serum concentration of HE4 in the EOC group was significantly higher than that in the benign group and the control group ( P＝0. 000) . The serum HE4 concentration in group EOC was significantly higher than that in benign group and control group (P＜0. 01),but there was no significant difference between benign group and control group (P＞0. 05). The positive rate of serum HE4 in the EOC group was 74. 5 (73/98),the positive rate of the benign group and the control group were 0,the difference between the three groups was statistically significant (P＝0. 000). The positive rate of serum HE4 in the EOC group was significantly higher than that in the benign group and the control group ( P＜0. 01), while the benign group and the control group had no statistical significance (P＞0. 05). The median survival time of EOC patients in low level HE4 group was 66. 2 months,while that in high level HE4 group was 36. 9. The difference between two groups was statistically significant (P＝0. 001). Conclusion The serum HE4 level of EOC patients was significantly higher than that of patients with benign ovarian tumors and healthy controls. The higher serum HE4 level,the worse the prognosis, and the shorter the survival time of patients. Therefore,the expression level of serum HE4 can be used for the diagnosis and prognosis of ovarian cancer.
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The epithelium of the human epididymis maintains an appropriate luminal environment for sperm maturation that is essential for male fertility. Regional expression of small noncoding RNAs such as microRNAs contributes to segment-specific gene expression and differentiated functions. MicroRNA profiles were reported in human epididymal tissues but not specifically in the epithelial cells derived from those regions. Here, we reveal miRNA signatures of primary cultures of caput, corpus, and cauda epididymis epithelial cells and of the tissues from which they were derived. We identify 324 epithelial cell-derived microRNAs and 259 tissue-derived microRNAs in the epididymis, some of which displayed regionalized expression patterns in cells and/or tissues. Caput cell-enriched miRNAs included miR-573 and miR-155. Cauda cell-enriched miRNAs included miR-1204 and miR-770. Next, we determined the gene ontology pathways associated with in silico predicted target genes of the differentially expressed miRNAs. The effect of androgen receptor stimulation on miRNA expression was also investigated. These data show novel epithelial cell-derived miRNAs that may regulate the expression of important gene networks that are responsible for the regionalized gene expression and function of the epididymis.
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The epithelium of the human epididymis maintains an appropriate luminal environment for sperm maturation that is essential for male fertility. Regional expression of small noncoding RNAs such as microRNAs contributes to segment-specific gene expression and differentiated functions. MicroRNA profiles were reported in human epididymal tissues but not specifically in the epithelial cells derived from those regions. Here, we reveal miRNA signatures of primary cultures of caput, corpus, and cauda epididymis epithelial cells and of the tissues from which they were derived. We identify 324 epithelial cell-derived microRNAs and 259 tissue-derived microRNAs in the epididymis, some of which displayed regionalized expression patterns in cells and/or tissues. Caput cell-enriched miRNAs included miR-573 and miR-155. Cauda cell-enriched miRNAs included miR-1204 and miR-770. Next, we determined the gene ontology pathways associated with in silico predicted target genes of the differentially expressed miRNAs. The effect of androgen receptor stimulation on miRNA expression was also investigated. These data show novel epithelial cell-derived miRNAs that may regulate the expression of important gene networks that are responsible for the regionalized gene expression and function of the epididymis.