Correlation of preoperative peripheral blood neutrophil-lymphocyte ratio and blood platelet-lymphocyte ratio and immune indexes with the prognosis of cervical cancer patients / 肿瘤研究与临床

Objective:To evaluate the value of preoperative peripheral blood neutrophil-lymphocyte ratio (NLR) and blood platelet-lymphocyte ratio (PLR) and immune indexes in the evaluation of the prognosis of cervical cancer patients.Methods:The clinical data of 283 patients with cervical cancer who underwent radical surgery in Shanxi Province Cancer Hospital from May 2017 to September 2018 were retrospectively analyzed, and 100 healthy people who underwent physical examination during the same period were collected as the healthy control group. Test results of blood cells and immune cells expressions of all subjects were collected. Peripheral blood NLR and PLR of cervical cancer patients, people in the healthy control group and cervical cancer patients with different pathological characteristics were compared. Kaplan-Meier method was used to make survival analysis and Cox regression risk model was used to analyze the factors influencing the prognosis of patients with cervical cancer.Results:The preoperative peripheral blood NLR and PLR in patients with cervical cancer was higher than that of the healthy control group (NLR: 2.53±1.35 vs. 2.00±1.21, t = 5.35, P < 0.001; PLR: 163±57 vs.144±38, t = 4.71, P = 0.006). Pathological results showed that there were no statistically significant differences in NLR and PLR in peripheral blood of cervical cancer patients with different pathological types, tumor diameter, vascular invasion, and nerve invasion (all P > 0.05), while there were statistically significant differences in NLR and PLR in peripheral blood of cervical cancer patients with different clinical staging and muscle wall invasion (all P < 0.05). When the proportions of the expression levels of preoperative CD3 positive cells, CD4 positive cells, CD8 positive cells, CD19 positive cells, CD56 positive cells, and CD127 positive cells were 60%-85%, 30%-40%, < 25%, 8%-15%, 15%-25% and < 5%, respectively, the overall survival of cervical cancer patients was the best. Univariate analysis showed that pathological type, clinical staging, vascular invasion, preoperative NLR, preoperative PLR,CD3 positive cells, CD4 positive cells, CD8 positive cells, CD19 positive cells, CD56 positive cells and CD127 positive cells were influencing factors of the overall survival of cervical cancer patients (all P < 0.05). Multivariate analysis showed that clinical staging, vascular invasion, preoperative NLR, preoperative PLR, and preoperative CD4 positive cells were independent influencing factors for the overall survival of cervical cancer patients (all P < 0.05). Conclusions:Preoperative high NLR and PLR in peripheral blood have a certain impact on the clinicopathological characteristics and poor prognosis of cervical cancer patients. When the immune cells in peripheral blood are in dynamic balance, the prognosis of cervical cancer patients is the best.

Analysis of clinicopathological features and factors influencing the survival of young breast cancer patients / 肿瘤研究与临床

Objective:To explore the clinicopathological characteristics and factors influencing the survival of young breast cancer patients with diagnostic age below 35 years, and to provide the basis for the prevention and treatment of young breast cancer patients.Methods:Epidemiological and clinicopathological data of young female patients with newly diagnosed breast cancer from Shanxi Province Cancer Hospital between January 2015 and December 2016 were retrospectively analyzed. The data included age at diagnosis, reproductive history, history of abortion, menopausal status, and immunohistochemical results. Univariate and multivariate analysis were performed by using Cox regression model.Results:A total of 118 young breast cancer patients were collected, and the median age was 31 years old. Among them, the vast majority of 118 young breast cancer patients were invasive cancer (113 cases, accounting for 95.8%); there were 65 cases (55.1%) with tumor diameter ≤ 20 mm, 61 cases (51.7%) at N 0 stage, and 112 cases (94.9%) at M 0 stage. The positive rates of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) were 73.7% (87/118), 69.5% (82/118) and 28.8% (34/118), respectively. Luminal B breast cancer was the predominant molecular subtype, accounting for 55.1% (65/118). By the end of follow-up (median follow-up period of 60 months), the overall survival rate of young breast cancer patients was 78.8%. Multivariate analysis showed that TNM staging was an independent factor affecting overall survival in young breast cancer patients ( HR = 7.858, 95% CI 2.924-21.120, P < 0.001). Conclusions:Young breast cancer patients have unique clinicopathological features and TNM staging is an independent factor affecting the prognosis. Individualized treatment helps to improve the quality of life and prolong the survival time of patients.

Clinical study of association between breast cancer and thyroid diseases / 肿瘤研究与临床

Objective:To investigate the association between breast cancer and thyroid diseases, and to provide evidence for the prevention and treatment of thyroid diseases in breast cancer patients.Methods:A total of 511 newly diagnosed breast cancer patients were recruited between March 2018 and August 2019 from Shanxi Province Cancer Hospital, and 303 age-matched newly diagnosed breast benign disease patients and 341 age-matched healthy controls were recruited during the same time-frame. Thyroid B-ultrasound and thyroid function test were performed in the three groups. By reviewing the medical records, the general and clinicopathological data of the patients were collected, and the differences in the prevalence of thyroid diseases among the three groups were compared. The changes of thyroid function in breast cancer patients before treatment, in the middle stage of chemotherapy and at the end of chemotherapy were compared.Results:Among breast cancer group, breast benign disease group and healthy control group, the differences in the prevalence rates of hypothyroidism [32.5% (166/511), 25.7% (78/303) and 21.7% (74/341)], thyroid nodules [50.7% (259/511), 43.2% (131/303) and 41.6% (142/341)] and Thyroid Imaging Reports and Data System(TI-RADS) grade 4 and above thyroid nodules [15.4% (40/259), 14.5% (19/131) and 4.9% (7/142)] were statistically significant (all P < 0.05). The abnormal rates of thyroid stimulating hormone (TSH) and free thyroxine (fT4) in breast cancer group were higher than those in breast benign disease group and healthy control group [34.1% (174/511) vs. 26.1% (79/303), 23.5% (80/341); 24.9% (127/511) vs. 8.6% (26/303), 3.2% (11/341)], and the differences were statistically significant (both P < 0.05). The levels of fT4, free three iodide thyroxine (fT3), thyroid immunoglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) in breast cancer patients before treatment, in the middle stage of chemotherapy and at the end of chemotherapy were statistically different (all P < 0.05). The abnormal rates of fT4, TgAb and TPOAb in the last chemotherapy cycle were lower than those before chemotherapy [11.5% (59/511) vs. 24.9% (127/511), 5.1% (26/511) vs. 17.4% (89/511), 11.9% (61/511) vs. 20.4% (104/511)] in breast cancer patients, and the differences were statistically significant (all P < 0.001). Conclusions:The breast cancer is associated with thyroid diseases. Clinicians should pay more attention to the changes of thyroid diseases and thyroid function during the treatment and in the follow-up process of breast cancer patients, so as to detect the thyroid diseases early and carry out standardized treatment.

Level of glypican 3 in primary liver cancer and its clinical significance / 肿瘤研究与临床

Objective:To investigate the levels of glypican 3 (GPC3) and alpha-fetoprotein (AFP) in the serum of patients with primary liver cancer and its diagnostic value in liver cancer.Methods:A total of 277 patients with primary liver cancer, 108 patients with gastric cancer, 40 patients with hepatitis alone, 19 patients with hepatitis combined with other cancers other than liver cancer and 54 healthy controls in Shanxi Provincial Cancer Hospital between June 2018 and January 2019 were collected. The serum samples from all patients were taken. Enzyme linked immunosorbent assay (ELISA) was used to detect GPC3 level in all specimens. Electrochemiluminescence was used to detect the level of AFP. The diagnostic value of GPC3 or AFP alone and a combination of both for liver cancer was also compared. The relationship between GPC3 and AFP was also analyzed.Results:The serum GPC3 level [median (interquartile range)] in primary liver cancer, gastric cancer, the hepatitis only, the hepatitis combined with other cancer and healthy control was 0.079 ng/ml (0.198 ng/ml), 0.048 ng/ml (0.044 ng/ml), 0.073 ng/ml (0.053 ng/ml), 0.050 ng/ml (0.018 ng/ml), 0.023 ng/ml (0.011 ng/ml), respectively. The GPC3 level in the primary liver cancer was higher than that in the gastric cancer, hepatitis combined with other cancers other than liver cancer, the healthy controls (all P < 0.05), and there was no statistically significant difference in the level of GPC3 between the primary liver cancer and the hepatitis only ( P = 0.520). The sensitivity and specificity of GPC3 for the diagnosis of primary liver cancer was 69.5% and 94.4%, respectively. The sensitivity and specificity of AFP for the diagnosis of primary liver cancer was 63.9% and 94.0%, respectively. The sensitivity and specificity of the combined detection of liver cancer was 80.2% and 94.3%, respectively. The ratio of positive likelihood ratio and negative likelihood ratio was 38.42, 27.73 and 67.01, respectively in liver cancer diagnosed with GPC3, AFP and both of them. The expression of serum GPC3 was associated with AFP ( r = 0.34, P < 0.01). Conclusions:The detection of GPC3 combined with AFP can increase the detection rate of primary liver cancer, and it has a certain clinical significance in the early screening and diagnosis of primary liver cancer.

Progress of the relationship between breast cancer and thyroid diseases / 肿瘤研究与临床

Breast cancer and thyroid diseases mostly occur in women, and both have seriously affected women's physical and mental health. Breast cancer patients have a higher risk of thyroid diseases before and after the onset of the disease compared with other malignant tumors. There are some common risk factors between them, and breast and thyroid are hormone-responsive organs, so they can also influence each other in some regulatory pathways. Iodine, thyroid hormone receptor and estrogen receptor are considered to be the possible pathogenesis of breast cancer. This paper explores the relationship between breast cancer and thyroid diseases with the help of researches in breast cancer, thyroid benign diseases, thyroid cancer, thyroid hormones and antibodies in recent years, so as to provide a basis for disease prevention and treatment.

A single center study on the relationship between the depth of remission and the efficacy of first-line TKI drugs / 中国医师杂志

Objective@#The aim of the study was to investigate association of response depth and prognosis in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)patients treated with first-line tyrosine kinase inhibitors (TKIs).@*Methods@#The clinicopathological data and prognosis information of patients with locally advanced or metastatic (ⅢB or Ⅳ) lung adenocarcinoma with EGFR classical (19del or 21L858R) mutation who were treated in our hospital from 2015 to 2016 were collected. The tumor remission depth [stable disease (SD), partial response (PR), complete response (CR)] was measured by recist 1.1 standard. The survival curve was drawn by Kaplan-Meier method and log rank test was performed.@*Results@#During the study period, 204 advanced lung adenocarcinoma patients with 19del or 21L858R mutation were treated with TKI drugs of the first generation. Among them, 24 patients were lost or unable to evaluate the efficacy, 20 patients were evaluated as progression disease (PD), 62 patients as SD, 98 patients as CR or PR. Disease control rate (DCR) and objective remission rate (ORR) were 88.9% and 54.4%, respectively. The median progression free survival time (PFS) was 12.6 months (95% CI: 10.9-14.4 months) and 13.1 months (95% CI: 11.6-14.7) for patients assessed as SD (group A) and CR or PR (group B), respectively, with no significant difference (P=0.27). Subgroup analysis showed that the median overall survival of patients with EGFR 19del and 21L858R mutations was 12.5 months (95% CI: 9.9-15.4) and 12.7 months (95% CI: 9.4-16.1), respectively, with no significant difference (P=0.66); Similar result was also observed in Group B with a median PFS of 13.9 months (95% CI: 12.3-15.5 months) and 12.3 months (95% CI: 9.5-15.1 months) in patients who had EGFR 19del or 21L858R mutations (P=0.41).@*Conclusions@#Response depth was not a positive predictor for prognosis in EGFR-mutant NSCLC patients treated with first-line TKIs.

Association between epidermal growth factor receptor mutation and chemotherapeutic efficacy in advanced non-small cell lung cancer patients / 中国医师杂志

Objective:The aim of the study was to investigate the association between epidermal growth factor receptor (EGFR) mutation and chemotherapeutic efficacy in advanced non-small cell lung cancer (NSCLC) patients.Methods:A total number of 490 patients with advanced non-small cell lung cancer were investigated in this retrospective study. Clinical outcomes were analyzed according to EGFR mutation status and mutation type based on Kaplan-Meier method and Cox regression model.Results:EGFR mutation was detected in 202 (41.2%) NSCLC patients. There was a trend that EGFR mutant patients had a higher response rate compared with wild type NSCLC patients, with non statistical significance (72.8% versus 66.0%, P=0.11). No difference was observed in progression free survival of first-line chemotherapy between EGFR negative and positive patients (6.00 versus 6.13 months, P=0.55). Patients harboring exon 19 deletion and exon 21 L858R point mutation derived similar progression free survival (PFS) (5.97 versus 6.23 months, P=0.79). Conclusions:EGFR mutation status and mutation type are not prognostic factors to first-line platinum-based chemotherapy in advanced NSCLC.

A single center study on the relationship between the depth of remission and the efficacy of first-line TKI drugs / 中国医师杂志

Objective The aim of the study was to investigate association of response depth and prognosis in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)patients treated with first-line tyrosine kinase inhibitors (TKIs).Methods The clinicopathological data and prognosis information of patients with locally advanced or metastatic (Ⅲ B or Ⅳ) lung adenocarcinoma with EGFR classical (19del or 21L858R) mutation who were treated in our hospital from 2015 to 2016 were collected.The tumor remission depth [stable disease (SD),partial response (PR),complete response (CR)] was measured by recist 1.1 standard.The survival curve was drawn by Kaplan-Meier method and log rank test was performed.Results During the study period,204 advanced lung adenocarcinoma patients with 19del or 21L858R mutation were treated with TKI drugs of the first generation.Among them,24 patients were lost or unable to evaluate the efficacy,20 patients were evaluated as progression disease (PD),62 patients as SD,98 patients as CR or PR.Disease control rate (DCR) and objective remission rate (ORR) were 88.9％ and 54.4％,respectively.The median progression free survival time (PFS) was 12.6 months (95％ CI:10.9-14.4 months) and 13.1 months (95％ CI:11.6-14.7) for patients assessed as SD (group A) and CR or PR (group B),respectively,with no significant difference (P =0.27).Subgroup analysis showed that the median overall survival of patients with EGFR 19del and 21L858R mutations was 12.5 months (95％ CI:9.9-15.4) and 12.7 months (95％ CI:9.4-16.1),respectively,with no significant difference (P =0.66);Similar result was also observed in Group B with a median PFS of 13.9 months (95％ CI:12.3-15.5 months) and 12.3 months (95％ CI:9.5-15.1 months) in patients who had EGFR 19del or 21L858R mutations (P =0.41).Conclusions Response depth was not a positive predictor for prognosis in EGFR-mutant NSCLC patients treated with first-line TKIs.

Correlation between pre-surgery thyroid function and lymphatic metastasis in patients with papillary thyroid carcinoma / 肿瘤研究与临床

Objective To explore the correlation between lymphatic metastasis and central lymph node metastasis and pre-surgery levels of serum thyrotropin (TSH), thyrobolulin (TG), anti-thyrobolulin antibodies (A-TG), anti-thyroid peroxidase antibodies (A-TPO) in patients with papillary thyroid carcinoma (PTC). Methods The clinical characteristics such as sex, age, tumor diameter, and some markers of thyroid function detection in 289 simple PTC cases were retrospectively analyzed, and their roles in lymphatic metastasis and central lymph node metastasis were discussed. Results Age < 45 years old (χ2= 5.86, P =0.02),multifocal(χ2=38.95, P<0.001), serum increased A-TG level(χ2=13.31,P <0.001) or A-TPO level (χ2= 7.30, P< 0.01) leaded to higher rate of lymphatic metastasis. Different TSH levels had different impact on lymphatic metastasis (χ2= 11.81, P = 0.02). When at 1.81-2.52 mU/L, the lowest rate of lymphatic metastasis was 34.68 %. Multivariable logistic regression analysis showed that focus (OR= 3.29, 95 % CI 1.85-5.52) and serum A-TG level (OR= 2.17, 95 % CI 1.11-4.26) were risk factors, whereas TSH at 1.81-2.52 mIU/L was more safe factor in simple PTC cases with lymphatic metastasis (OR= 0.28,95 % CI 0.09-0.85). Different groups of age (χ2= 11.54, P= 0.001), focal (χ2= 38.95, P< 0.001), serum TG level (χ2=9.01, P=0.01), A-TG level (χ2=14.51, P <0.001) or A-TPO level (χ2= 6.78, P= 0.02) leaded to statistically different central lymph node metastasis ending; further analysis showed that age (OR= 0.96, 95 % CI 0.94-0.98) and focus (OR= 5.47, 95 % CI 3.09-9.69) were risk factors of central lymph node metastatic in PTC patients. Conclusion Higher pre-surgery serum A-TG level and multifocal predict lymphatic metastasis, TSH level in 1.81-2.52 mU/L indicates lower rate of lymphatic metastasis, but age<45 years old and multifocal PTC patients are apt to occur central lymph node metastasis.

Clinical value of the VEGF-C and VEGF-R3 in peripheral blood of patients with lung cancer / 国际肿瘤学杂志

Objective To investigate the relationship between the expression of vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGF-R3) in peripheral blood of patients with lung cancer and the pathological characteristics, and to assess the ability to evaluate lymphatic and distant metastasis of the two marks.Methods VEGF-C and VEGF-R3 were detected by enzyme-linked immunosorbent assay (ELISA) in 124 patients with lung cancer and 30 normal controls, and used to analyze the relationship with the pathological characteristics of lung cancer.Results The serum levels [M(QR)] of VEGF-C and VEGF-R3 in patients with lung cancer were 283.57 (120.70) pg/ml and 62.72 (43.02) ng/ml, significantly higher than the control whose VEGF-C and VEGF-R3 were 234.62 (129.20) ng/ml and 43.08 (17.07) pg/ml, respectively (Z=-2.840, P=0.005;Z=-3.834, P<0.001).No correlation was found between the expression of VEGF-C and age, sex, primary tumor site, T stage (Z=-0.949, P=0.343;Z=-0.454, P=0.649;Z=-1.168, P=0.243;Z=-1.694, P=0.090).But the expression of VEGF-C was significantly related with pathologic type, N stage and M stage (χ2=8.829, P=0.012;χ2=27.148, P<0.001;Z=-2.221, P=0.026).However, the expression of VEGF-R3 was not correlated with age, sex, the site of the primary lesion, pathological type and T, N, M stage (Z=-0.558, P=0.577;Z=-0.599, P=0.549;Z=-0.703, P=0.482;χ2=1.166, P=0.558;Z=-0.680, P=0.496;χ2=0.353, P=0.950;Z=-1.523, P=0.128).Conclusion The expressions of VEGF-C and VEGF-R3 in patients with lung cancer are higher than those in normal control, and the expression of VEGF-C is related with patho-logic type, N stage and M stage.The detection of VEGF-C in peripheral blood of lung cancer is expected to be an assistant marker for the evaluation of lymph node metastasis and blood metastasis, but VEGF-R3 does not show its value.

Clinical value of circulating tumor cells detection in patients with colorectal cancer / 肿瘤研究与临床

Objective To investigate the association between the positive rate of circulating tumor cells (CTC) and clinicopathological parameters, recurrence and metastasis in patients with colorectal cancer. Methods 7.5 ml peripheral blood of 138 cases of newly diagnosed colorectal cancer who met inclusion criteria, 82 post-operative cases of colorectal cancer and 34 healthy controls were collected. The CTC was enriched by beads which packaged the anti epithelial cell adhesion molecule and counting the CTC (CK+ DAPI+ CD45-). To investigate the association between the preoperative positive rate of CTC and clinicopathological parameters, and the relationship between the positive rate of CTC and recurrence and metastasis in post-operative colorectal cancer patients who have not accepted any therapy more than one month. Results The positive rate of CTC in patients with colorectal cancer and healthy controls were 47.1%(65/138), and 0 (0/34) respectively, and the difference was statistically significant (χ2= 25.743, P 0.05); The significant association between the positive rate of CTC and N or M staging was found. CTC positive rates in N0, N1, N2 stage were 38.3 %(23/60), 37.9 % (11/29), and 63.9 % (23/36) respectively (χ2= 6.819, P= 0.033); CTCs positive rates of M0, M1 stage were 38 . 0 % ( 38/100 ) and 71 . 1 % ( 27/38 ) respectively , and there was a statistical difference (χ2= 12.074, P= 0.001). In 82 post-operative cases of colorectal cancer, the positive rates of CTC were 51.6 % (32/62) and 90.0 % (18/20) in non-recurrence and recurrence, respectively, and the difference was statistically significant (χ2=9.365, P=0.002). Conclusion CTC detection may assess the occurrence of metastasis and recurrence in colorectal cancer patients.

Influencing factors of thyroid disease in breast cancer patients / 肿瘤研究与临床

Objective To understand the status and influencing factors of thyroid disease in breast cancer patients, and to identify the high-risk people with thyroid disease. Methods Breast cancer patients were continually collected from Jan 2016 to Mar 2016 in Shanxi Cancer Hospital. Age, surgery time, the state of thyroid disease, medical record, the general condition, immunohistochemistry and pathological findings, thyroid B-mode ultrasonography were investigated respectively. All cases were divided into two groups according to whether to suffer from thyroid disease or not. The influencing factors for thyroid disease in patients with breast cancer were screened. Logistic regression was used for univariate and multivariate analysis. Results A total of 293 cases (69.3 %) suffered from thyroid disease in 423 breast cancer patients. The univariate analysis showed that prevalence rate of thyroid disease had statistical differences in age [<50 years old:49.5%(145/293) vs. 76.1%(99/130); ≥50 years old:50.5%(148/293) vs. 23.9%(31/130);χ2=24.297, P<0.001], body mass index [18.5-23.9 kg/m2:41.0%(120/293) vs. 52.3%(68/130);24.0-27.9 kg/m2:45.4%(133/293) vs. 40.8 % (53/130); ≥28.0 kg/m2: 13.7 % (40/293) vs. 6.9 % (9/130); χ2= 6.395, P=0.041], menopausal state [not: 59.7%(175/293) vs. 77.7%(101/130); yes: 40.3%(118/293) vs. 22.3%(29/130);χ2=12.443, P<0.001], estrogen receptor (ER) [ER--ER+: 44.0%(129/293) vs. 56.9%(74/130);ER++ - ER+++: 56.0 % (164/293) vs. 43.1 % (56/130); χ2 = 5.951, P= 0.015]. There were no significant differences in the times of pregnancy and production, history of abortion, progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), triple negative breast cancer, T stage, N stage, histological grade and TNM stage (P> 0.05). Multivariate analysis showed that the risk factors were age (OR= 3.928, 95 %CI=1.819-8.482, P<0.001) and ER++-ER+++(OR= 1.696, 95 %CI= 1.094-2.628, P= 0.018). Conclusion Age≥50 and ER++-ER+++are the major influencing factors of thyroid disease for patients with breast cancer.

Influencing factors of thyroid disease in breast cancer patients / 肿瘤研究与临床

Objective To understand the status and influencing factors of thyroid disease in breast cancer patients, and to identify the high-risk people with thyroid disease. Methods Breast cancer patients were continually collected from Jan 2016 to Mar 2016 in Shanxi Cancer Hospital. Age, surgery time, the state of thyroid disease, medical record, the general condition, immunohistochemistry and pathological findings, thyroid B-mode ultrasonography were investigated respectively. All cases were divided into two groups according to whether to suffer from thyroid disease or not. The influencing factors for thyroid disease in patients with breast cancer were screened. Logistic regression was used for univariate and multivariate analysis. Results A total of 293 cases (69.3 %) suffered from thyroid disease in 423 breast cancer patients. The univariate analysis showed that prevalence rate of thyroid disease had statistical differences in age [<50 years old:49.5%(145/293) vs. 76.1%(99/130); ≥50 years old:50.5%(148/293) vs. 23.9%(31/130);χ2=24.297, P<0.001], body mass index [18.5-23.9 kg/m2:41.0%(120/293) vs. 52.3%(68/130);24.0-27.9 kg/m2:45.4%(133/293) vs. 40.8 % (53/130); ≥28.0 kg/m2: 13.7 % (40/293) vs. 6.9 % (9/130); χ2= 6.395, P=0.041], menopausal state [not: 59.7%(175/293) vs. 77.7%(101/130); yes: 40.3%(118/293) vs. 22.3%(29/130);χ2=12.443, P<0.001], estrogen receptor (ER) [ER--ER+: 44.0%(129/293) vs. 56.9%(74/130);ER++ - ER+++: 56.0 % (164/293) vs. 43.1 % (56/130); χ2 = 5.951, P= 0.015]. There were no significant differences in the times of pregnancy and production, history of abortion, progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), triple negative breast cancer, T stage, N stage, histological grade and TNM stage (P> 0.05). Multivariate analysis showed that the risk factors were age (OR= 3.928, 95 %CI=1.819-8.482, P<0.001) and ER++-ER+++(OR= 1.696, 95 %CI= 1.094-2.628, P= 0.018). Conclusion Age≥50 and ER++-ER+++are the major influencing factors of thyroid disease for patients with breast cancer.

Detection and clinical significance of circulating tumor cells in gastric cancer / 中华胃肠外科杂志

The death of patients with gastric cancer is mainly due to its recurrence and metastasis, and circulating tumor cell (CTC) is the necessary condition of metastasis. As liquid biopsy, CTC detection has its certain clinical significance. The detection is required after enrichment because circulating tumor cells are rare. Many enrichment methods have been developed: methods based on physical characteristics of TCT, like density, size and dielectric properties and so on; immunogenicity, like Cell Search System; and microfluidic chip technology. The immunofluorescence is commonly used to identify CTC in gastric cancer and the isolated CTC can also be used for the following analysis on the level of nucleic acid, protein and gene regulation. Detection of CTC in gastric cancer is helpful to judge the prognosis, assess staging, monitor the curative effect and guide the development of drug. There are many challenges for clinical transformation of CTC: the lower enrichment efficiency, the less specific surface markers, the uncertain diagnostic efficiency and so on, but it also has the good research prospect because it is non-invasive, repeatable and can real-time monitor the condition and guide the clinical treatment compared with pathological biopsy. In this paper, the detection and identification methods, and clinical value of CTC in gastric cancer patients are reviewed.

Association of expressions and gene polymorphisms of leptin receptor with breast cancer / 肿瘤研究与临床

Objective To evaluate the association of expressions and gene polymorphism of leptin receptor (LEPR) in breast cancer with tumorigenesis,development and clinicopathologic factors.Methods The immunohistochemical method and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to evaluate LEPR expressions and LEPR Gln223Arg polymorphism in 150 cases with breast cancer,80 cases with benign breast lesions,50 cases with corresponding normal breast tissue and 128 healthy controls.Results The expression rate of LEPR genes in breast cancer tissues was significantly higher than that in benign breast lesions and that in corresponding normal breast tissues [70.67 ％ (106/150) vs 56.25 ％ (45/80) vs 44.00 ％ (22/50),P ＜ 0.005].In breast cancer patients,LEPR gene Gin223Arg genotype polymorphism (GG,GA and AA) frequencies were 70.00 ％ (105 cases),16.67 ％ (25 cases) and 13.33 ％ (20 cases),which were significantly different from those in the benign breast lesions [82.50 ％ (66 cases),13.75 ％ (11 cases),3.75 ％ (3 cases)],those in corresponding normal breast tissues [82.00 ％ (41 cases),14.00 ％ (7 cases),4.00 ％ (2 cases)] or those in the health controls [82.81％ (106 cases),14.85 ％ (19 cases) and 2.34 ％ (3 cases)] (X2 =11.56,P =0.003),while the differences of GG,GA and AA genotype requencies among the breast benign disease group,cancer adjacent normal breast group and healthy control group were not statistically significant (P ＞ 0.05).The frequencies of alleles genes in breast cancer patients (G and A) were 78.33 ％ (235 cases) and 21.67 ％ (65 cases),and the differences were statistically significant compared with those in the benign disease group or in healthy control group (X2 =12.52,P =0.001).The positive expression rate of LEPR gene in patients with lymph node metastasis was 87.8 ％,which was higher than that in patients with no lymph node metastasis (60.2 ％) (P =0.02).According to the results of multivariable analyses,high expression of LEPR gene,LEPR Gin223Arg gene polymorphisms and increased waist-hip ratio (WHR) were risk factors for breast cancer (all OR ＞ 1).Conclusion High expression of LEPR,LEPR Gln233Arg polymorphism and the elevated WHR may be correlated with breast cancer.

The diagnostic value of human epididymis protein 4 and carbohydrate antigen 125 for patients with ovarian neoplasms / 国际肿瘤学杂志

Objective Toevaluatethediagnosticvalueofhumanepididymisprotein4(HE4)andcar-bohydrate antigen 1 25 (CA1 25 )for distinguishing between benign and malignant ovarian neoplasms.Methods 1 1 09 patients with ovarian neoplasms were enrolled in this study,serum concentration of HE4 and CA1 25 was assayed using ELISA technique.And the markers were evaluated for significance separately and in combination. Results 1SerumlevelsofHE4andCA125weresignificantlyhigherinpost-menopausalwomenthanthosein pre-menopausal women(t=8.40,P<0.05;t=7.02,P<0.05).In addition,the more children the patients born,the higher serum levels of these two markers were(F=1 5.36,P<0.05;F=1 3.00,P<0.05).2 Serum HE4 levels were significantly higher in the ovarian cancer patients compared with those seen in patients with benign or borderline tumor(t=1 3.68,P<0.05;t=1 4.94,P<0.05).Serum CA1 25 levels were significantly higher in the ovarian cancer patients compared with those seen in patients with benign or borderline tumor(t=1 4.1 6,P<0.05;t=1 7.27,P<0.05).Morever,it also appared in the ovarian cancer patients with ascites and vascular embolism.Morever,the levels of HE4 were significantly higher in the ovarian cancer with ascites and vascular embolism than without it(t=7.08,P<0.05;t=4.41,P<0.05),the levels of CA125 were signifi-cantly higher in the ovarian cancer with ascites and vascular embolism than without it(t=9.67,P<0.05;t=4.75,P<0.05).3 During follow-up,serum HE4 and CA1 25 levels significantly decreased at 3 months after operation(t=9.86,P<0.05;t=5.12,P<0.05).4 Receiver operating characteristic curve,ROC)analysis revealed that no difference was observed in AUC values for HE4,CA1 25 and risk of ovarian malignancy algo-rithm(ROMA).5 Compared to CA1 25 ,HE4 had significantly higher specificity and lower sensitivity.Howev-er,sensitivity were increased when the two markers were combined with each other.However,the sensitivity of combination with two markers was higher than single detection and ROMA,but the specificity was lower in com-bination with two markers than single detection and ROMA.If we divide the ROMA by a woman′s menopausal status,ROMA has a higher sensitivity (73.84%,84.1 9%) and lower specificity (66.06%,66.67%). Conclusions ThelevelsofCA125hasahighsensitivity,andthelevelsofHE4isahighspecificity.CA125 combined with HE4 can provide a more sensitivity and accurate predictor of ovarian cancer than either alone.

Diagnostic value and prognosis assessment of ProGRP for small cell lung cancer / 中华检验医学杂志

Objective The purpose of this study was to discuss the clinical significance of serum levels of Pro-gastrin-releasing peptide (ProGRP) in diagnosis,therapy monitoring and prognosis in patients with small cell lung cancer (SCLC).Methods Clinical diagnostic trial.Serum levels of ProGRP were measured by ELISA assays in 413 SCLC patients,418 NSCLC,120 with benign pulmonary diseases patients and 200 healthy subjects.Patients were recuited by the Shanxi Cancer Hospital from Dec.2005 to Oct.2008.Three hundreds and sixty-eight patients with SCLC were followed up from Dec.2005 to Oct.2011.The receiver operating characteristic curves (ROC) was used to set the cut-off value of ProGRP and the area under ROC (ROC-AUC).The sensitivity and specificity of ProGRP were analyzed for diagnosing SCLC.The survival analysis was performed by the Kaplan-Meier method and Cox's proportional hazards model for multivariate analysis of prognosis.Results Using healthy subjects group as control,the largest Youden index point of ROC was used to set the cut-off values of ProGRP and NSE (45.3 ng/L and 12.4 ng/L).The ROC-AUC of ProGRP was 0.798 (95％ CI:0.746-0.850)the sensitivity and specificity were 79.2％,98.1％ respectively.The AUC of NSE was 0.786(95％ CI:0.726-0.746),the sensitivity and specificity were 71.9％,96.7％ respectively; Combing detection of ProGRP and NSE,the sensitivity and specificity were 88.1％,95.8％ respectively.Serum levels of ProGRP in healthy subjects,benign pulmonary diseases,NSCLC and SCLC groups were 6.9 (5.3-8.6),36.8 (26.3-43.4),21.3 (18.6-35.2) and 1758.7 (368.4-2967.3) μg/L respectively.The serum levels of ProGRP in SCLC groups were significantly higher than those in the healthy group,benign pulmonary diseases group and NSCLC group (H =103.66,P =0.000).Serum levels of ProGRP in SCLC at stage Ⅰ-],stage m,stage Ⅳ were 543.3 (256.8-843.2),1440.6 (1042.4-2543.3) and 1897.6 (1586.5-3958.7) μg/L,respectively (H =25.974,P =0.000).Serum levels of ProGRP in 165 SCLC patients with complete remission(CR) were significantly declined after treatment (U =11.65,P ＜ 0.01).The levels of ProGRP in 146 SCLC patients with partial remission(PR) slowly decreased (U =9.17,P ＜ 0.01).Thirty-nine cases with progressive disease (PD)and 63 cases with stable disease(SD) presented elevated ProGRP levels (U =3.314,P ＜ 0.001 ; U =2.54,P ＜ 0.01,respectively).By the end of October 31st 2011,a total of 368 cases with SCLC were followedup.Ratio of follow-up was 89.1％.There were 56 deaths in 119 SCLC patients with ProGRP ＜ 1000 μg/L (median time =16.0 months,4-23 months) ; 159 deaths in 249 with ProGRP ＞ 1000 μg/L (median survival time =12.0 months,2-18 months).Median survival time of the two groups showed significant differences(x2 =11.04,P =0.001).Multivariate analysis by Cox's proportional hazards model revealed that ProGRP was independent prognostic factor related to the overall survival (OS) of SCLC patients.Conclusions The serum ProGRP is valuable tumor marker for diagnosis,treat monitoring and prognosis of SCLC.It's important to predict relapses and recurrence of diseases earlier,instruct therapy and prognosis assessment.

Value of serum phosphopyruvate hydratase protein for the diagnosis of cerebral injuries in patients with brain malignant tumor / 肿瘤研究与临床

ObjectiveTo study the value of serum phosphopyruvate hydratase PH protein for the diagnosis of cerebral injuries in patients with brain malignant tumor.MethodsSerum PH protein levels were detected by enzyme-linked immunosorbent assay in 56 patients with brain malignant tumor. Compare the differences among the status of cerebral injuries.And compare the differences among the patients with general with different radiotherapy methods 32 cases,three dimensional conformal radiothrapy 24 cases,and different peritumoral brain edema levels(cmild 18 cases, moderate ao cases severe 30 cases). Results Before radiotherapy the levels of serum PH protein in patients and the health control were (4.12±0.56),(4.66±0.62)μg/L,no significant differece(P＞0.05).And there was also no significant difference between the before and after radiotherapy for the cerebroma,the levels were(7.84±0.72) μg/L,(t=3.89,P=0.001 ).The PH levels of general radiation therapy and three dimensional comformal radiotherapy were (13.59±0.92),(6.14±0.52)μg/L.There was cignificant difference(P=0.002) After radiotherapy,The levels of serum PH protein of the different dropsical degree,mild,moderate and severe were(4.47:±0.55),(6.17±0.62),(15.21±0.86) μg/L, respectively,showing significant difference(F=15.61,P=0.0001).The therapies influenced the serum PH levels(P＜0.05)ConclusionHigh levels of serum PH protein are associated with severe cerebral injuries in brain malignant tumor.So high serum PH level may serve as an progressive predictor of the injury.

Effect of leptin on proliferation and apoptosis of human breast cancer cell MCF-7 / 肿瘤研究与临床

Objective To observe the effect of leptin on proliferation and apoptosis of breast cancer MCF-7 cell line,and to explore the effect of leptin on occurrence and development of breast cancer.Method The MCF-7 cell line was treated with different concentration of leptin in vitro.Cell proliferation was evaluated by MTT assay. Distribution of cell cycle was determined by flow cytomery, meanwhile the rates of apoptosis were estimated on the basis of Annexin V-FITC/PI apoptosis detection. Results When treated with different concentration of leptin for 24 h, 48 h and 72 h, they could significantly induce the proliferation of MCF-7 cells by MTT method.There was not interaction between concentration of leptin and time course (F=0.919,P=0.523).The main effect of concentration of leptin and time course was statistically significant (F=12.699,P=0.000;F=647.881, P=0.000). Compared 200 ng/ml and 400 ng/ml with the control group, we found the difference was statistically significant by multiple comparison (P=0.007,P=0.000,respectively).The difference was also statistically significant among time course by multiple comparison (P=0.000,respectively).By the flow cytometry analysis,it was found that the 100 ng/ml and 400 ng/ml leptin groups could change the distribution of cell cycle of MCF-7 cell line after 48 h. Compared with control group, the cell number decreased by 14.42 ％ in G0/G1 phase (F=10.464, P=0.044),but increased by 7.57 ％ and 22.19 ％ respectively in S phase (F=47.361,P=0.005).The difference was not statistically significant in G2/M phase (F=1.77, P=0.311).However, the effect of apoptosis inhibition was not obvious. Conclusions Leptin could stimulate the proliferation of MCF-7 cell line and change the distribution of cell cycle.But leptin could not inhibit apoptosis of MCF-7 cell line.It suggested that leptin may serve as a risk factor of breast cancer development.

Associations between expressions of leptin and leptin receptor genes in breast cancer / 肿瘤研究与临床

Objective To evaluate the association of expressions of leptin and leptin receptor in breast cancer with tumorigenesis and development and clinicopathologic factors.Methods The expression of leptin and leptin receptor was performed in 132 cases of breast cancer,66 cases of benign breast lesions,and 30 cases of corresponding normal breast tissue by using immunohistochemical methods. ResultsThe expressions of leptin and leptin receptor were 76.5 ％ (101/132) and 70.5 ％ (92/132).It was significantly higher than that in benign breast lesions 56.1％ (37/66) and 56.1％ (37/66),and corresponding normal breast tissues 46.7 ％ (14/30) and 43.3 ％ (13/30) (x2 =8.72,P =0.003,x2 =4.04,P =0.044,x2 =10.57,P =0.001and x2 =7.94, P =0.005).The level of leptin expression showed a significant correlation with the level of leptin receptor (r =0.307,P ＜ 0.05).The expression of leptin and leptin receptor in breast cancer tissue were not significantly related to ages,menopause,tumor size,classification,pathological type,distant metastasis,ER and PR expression (P ＞ 0.05).The positive rate of leptin in patients with lymph node metastasis was 91.7 ％,which was significantly higher than that in patients without lymph node metastasis (67.9 ％,x2 =10.65,P =0.002).Conclusions The expressions of leptin and leptin receptor have a significant correlation with breast cancer and may have the promoting effect on the carcinogenesis and development of breast cancer.