PCDHGA10 as a Potential Biomarker of Lung Squamous Cell Carcinoma Based on Bioinformatics and Experimental Verification.

Procalcitonin gamma subfamily A, 10 (PCDHGA10) is a member of the procalcitonin gamma gene cluster, which is associated with neuronal synapse development. However, there are lack of studies on the role and potential prognostic value of PCDHGA10 in lung squamous cell carcinoma (LUSC). We analyzed the RNAseq data of PCDHGA10 to compare their expression differences. Then survival analysis, tumor microenvironment (TME) analysis, and mutation analysis were carried out. Additionally, we performed gene ontology (GO) and kyoto gene encyclopedia (KEGG) enrichment analyses to explore potential signal pathways. PCDHGA10 protein expression was evaluated using immunohistochemistry (IHC) on tissue microarrays (HLugS180Su02). By microarray analysis and database analysis, we found that PCDHGA10 was significantly highly expressed in LUSC. Sufferers with elevated PCDHGA10 levels exhibited a worse prognosis, according to the survival analysis. The PCDHGA10 mutation was also linked to LUSC patient prognosis. Besides, PCDHGA10 was closely related to tumor immune cell infiltration and immune checkpoints. In conclusion, PCDHGA10 is expected to become a new molecular marker for LUSC.

[Exploring the Role of PCDHGB4 in the Occurrence of Lung Squamous Cell Carcinoma Based on Bioinformatics Analysis].

BACKGROUND: Lung squamous cell carcinoma (LUSC) is a subtypes of non-small cell lung cancer (NSCLC). It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway. Protocadherin-gamma subfamily B4 (PCDHGB4) as a family member in LUSC was rarely reported. The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC using bioinformatics methods. METHODS: The Cancer Genome Atlas (TCGA), cBioPortal and UALCAN databases were used to analyze the expression, prognosis, clinicopathological features, immune cell infiltration, immune regulatory genes, immune checkpoint inhibitors (ICIs), and methyltransferases of PCDHGB4 in LUSC. At the single cell level, we analyzed the clustering results of cell subtypes and the expression of PCDHGB4 in different immune cell subpopulations. In addition, we compared the promoter methylation levels of PCDHGB4 in LUSC tissues and normal tissues and performed protein-protein interaction and mutation analysis. Finally, enrichment analysis was performed based on the differentially expressed genes. RESULTS: Bioinformatics analysis results showed that the expression level of PCDHGB4 in LUSC tissues was lower than that in normal tissues. Survival analysis showed that increased PCDHGB4 expression was associated with poor prognosis. Single-cell sequencing analysis showed that PCDHGB4 was expressed in T cells, monocytes or macrophages, and dendritic cells. It was further found that PCDHGB4 played an important role in tumor immunity and confirmed that PCDHGB4 was associated with immune checkpoints, immune regulatory genes, and methyltransferases. Besides, enrichment analysis revealed that PCDHGB4 was involved in multiple cancer-related pathways. CONCLUSIONS: The expression of PCDHGB4 was low in LUSC. PCDHGB4 was related to the poor prognosis of patients, and PCDHGB4 was closely related to the infiltration and pathway of tumor immune cells. PCDHGB4 may be a potential prognostic marker and a new target for immunotherapy in LUSC.

Function and mechanism of GBP1 in the development and progression of cervical cancer.

Guanylate binding protein 1 (GBP1) is the most concerned member of the GBP family, which has a series of effects such as anti-infection and anti-angiogenesis. Its role in malignant tumors including cervical cancer is still controversial. We aim to explore the effects of GBP1 on cervical cancer through bioinformatics and related experiments. In this study, we first found that GBP1 was generally expressed in cervical cancer in various online databases and was closely related to immune invasion. Secondly, we used multicolor immunofluorescence technology to verify the expression of GBP1 in cervical cancer tissues and its relationship with immune invasion, and explored its relationship with the prognosis of patients with cervical cancer. Knockdown and overexpression assays of GBP1 in vitro were used to prove GBP1 as a potential oncogene of cervical cancer, and its carcinogenicity was verified by in vivo experiment. In order to explore the potential mechanism of GBP1 in promoting cancer, RNA-seq was performed on GBP1 overexpression and knockdown expression cell lines, and GBP1 knockdown and overexpression were found to be associated with many RNA alternative splicing events, suggesting that GBP1 maybe a RNA binding protein (RBP) which affect the biological characteristics of cervical cancer cells through the alternative splicing pathway. However, the later RNA binding protein immunoprecipitation (RIP) assay proved that GBP1 was not a direct alternative splicing factor, while the co-immunoprecipitation (CoIP)-mass spectroscopy (MS) assay combined with protein protein interaction (PPI) analysis proved that 8 alternative splicing factors including Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) were interacting proteins of GBP1. Combined with the existing reports and the results of RNA-seq alternative splicing analysis, it is speculated that GBP1 may regulate the alternative splicing of CD44 protein by binding to interacting protein-HNRNPK, and thus play a role in promoting cancer in cervical cancer.

DNA mismatch repair system regulates the expression of PD-L1 through DNMTs in cervical cancer.

BACKGROUND: Cervical cancer (CC) is a potential clinical application of PD-1/PD-L1 inhibitor. We aimed to study the mechanism of DNA mismatch repair (MMR) system regulating the expression of PD-L1 in CC through DNA methyltransferase (DNMTs). METHODS: We collected pathological specimens from 118 cases of CC to analyze the relationship between PD-L1 expression and DNMTs in different MMR states. RNA interference (RNAi) technique was used to simulate the formation of CC cell line with MMR deficiency (dMMR) state, and subcutaneous tumor formation experiment was carried out in nude mice to verify the relationship between PD-L1 expression and DNMTs in MMR state. RESULTS: The PD-L1 positive rate in 118 cases of CC was 58.47%, while the microsatellite instability (MSI) status accounted for 5.93%. There was a significant difference in the expression of PD-L1 between patients within the dMMR and MMR proficient (pMMR) groups (χ2 = 21.405, P < 0.001). Subcutaneous inoculation after infection of Siha cells led to successful tumorigenesis in nude mice, accompanied by a significant increase in the level of PD-L1 expression in the mouse tumors, while the expression level of MLH1 and MSH2 protein decreased significantly. We also found that PD-L1 expression was closely related to the expression of DNMTs. CONCLUSION: PD-L1 is universal expressed on the surface of CC cells, dMMR status enhances the expression of PD-L1 on the surface of CC cells, dMMR states of CC are related to the demethylation status of the PD-L1 gene promoter region.

[Exploring the Role of DKK1 in the Occurrence of Lung Adenocarcinoma Based on the Analysis of Bioinformatics].

BACKGROUND: Lung cancer is the most common malignant tumor in China, lung adenocarcinoma (LUAD) is the main type of lung cancer, which is a serious threat to people's life and health. At present, there are fewer studies on the role of Dikkopf1 (DKK1) in lung adenocarcinoma. The aim of this study was to investigate the role and potential prognostic value of DKK1 in the development of lung adenocarcinoma by bioinformatics methods. METHODS: Several databases, such as genotype-tissue expression (GTEx), The Cancer Genome Atlas (TCGA) and tumor-immune system interactions database (TISIDB), were used to analyze the expression, clinicopathological features, immune cell infiltration, prognosis and methylation of DKK1 in lung adenocarcinoma. Then, linked immune cell infiltration Omics database was used to analyze the co-expressed genes of DKK1 and their functional enrichment. Finally, 59 pathological samples of paraffin-embedded lung adenocarcinoma patients who underwent surgery at the Affiliated Cancer Hospital of Xinjiang Medical University between 2016 and 2017 were collected for the validation of the prognostic value of expression by immunohistochemistry (IHC) test. RESULTS: The results of bioconfidence analysis showed that the expression level of DKK1 in lung adenocarcinoma tissues was higher than that in normal tissues, the expression in advanced cancers was higher than that in early stages, and the experimental validation revealed that among 59 cases of lung adenocarcinoma, there were 15 cases of negative expression (25.4%), 18 cases of weakly positive expression (30.5%), and 26 cases of strongly positive expression (44.1%). The different expression of DKK1 is related to methylation, prognosis and the activities of various immune cells. Functional enrichment shows that DKK1 may be involved in skin development and cell-substrate junction, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis shows that DKK1 is related to ABC transporters. Bioinformatics analysis and clinical case specimens showed that high DKK1 expression was associated with poorer prognosis in patients with lung adenocarcinoma. CONCLUSIONS: High expression of DKK1 in lung adenocarcinoma is associated with poor prognosis. DKK1 is closely associated with tumor immune cell infiltration and pathways. DKK1 can be considered as a potential prognostic marker and a novel target for immunotherapy of lung adenocarcinoma.

Clinical application of common inflammatory and nutritional indicators before treatment in prognosis evaluation of non-small cell lung cancer: a retrospective real-world study.

Objective: To evaluate the prognostic value of common clinical inflammatory and nutritional indicators before treatment in patients with non-small cell lung cancer in the real world. Method: A total of 5,239 patients with pathologically confirmed non-small cell lung cancer from 2011 to 2018 in the Affiliated Cancer Hospital of Xinjiang Medical University were selected. Their inflammatory and nutritional indicators (RDW, PDW, NLR, LMR, NMR, PLR, SII, PNI, TP, ALB, CYRFA21-1, CEA, CA125, NSE, α1-globulin, α2-globulin, ß1-globulin, ß2-globulin, and γ-globulin) before treatment were collected. From the total number, 1,049 patients were randomly sampled (18 to 20% of patients each year) and used as the validation set; the remaining 4,190 patients were used as the training set. According to the eighth edition of the guidelines for the diagnosis, treatment, and stage risk stratification of lung cancer, the patients were divided into four groups: stage I/II operable, stage III operable, stage III inoperable, and stage IV. We used the X-tile software to intercept and classify the cut-off values of each index in the validation set. Univariate and multivariate Cox proportional-hazard regression were used to screen the independent risk factors affecting the prognosis of non-small cell lung cancer and establish a prognostic model for 1, 3, and 5 years. The validation set was used to verify its performance. Finally, the Kaplan-Meier curve was used to assess the survival rate, and the corresponding nomogram was established for clinical use. Results: After screening, no effective indicators were found in the stage I/II operable group. RDW and CA125 were effective indicators for the stage III operable group (cut-off values were 14.1 and 9.21, respectively, compared with the low-value group; univariate HR was 2.145 and 1.612, and multivariate HR was 1.491 and 1.691, respectively). CYRFA21-1 and CA125 were effective prognostic indicators for the stage III inoperable group (cut-off values were 10.62 and 44.10, respectively, compared with the low-value group; univariate HR was 1.744 and 1.342, and multivariate HR was 1.284 and 1.304, respectively). CYRFA21-1, CA125, NLR, and α1-globulin were effective indicators of prognosis in stage IV (cut-off values were 3.07, 69.60, 4.08, and 5.30, respectively, compared with the low-value group; univariate HR was 1.713, 1.339, 1.388, and 1.539; and multivariate HR was 1.407, 1.119, 1.191, and 1.110, respectively). The model was constructed with the best validation power in stage IV patients (C-index = 0.733, 0.749, and 0.75 at 1, 3, and 5 years, respectively). Conclusion: For patients with stage III and IV non-small cell lung cancer, some inflammatory markers, serum tumor markers, and nutritional indicators are independent prognostic factors. Combined with the general data of patients, the constructed prognostic evaluation model has the best efficacy in patients with stage IV and can be widely used in clinical practice.

Ferroptosis-related genes in cervical cancer as biomarkers for predicting the prognosis of gynecological tumors.

Background: Ferroptosis has been identified as a potent predictor of cancer prognosis. Currently, cervical cancer ranks among the most prevalent malignant tumors in women. Enhancing the prognosis for patients experiencing metastasis or recurrence is of critical importance. Consequently, investigating the potential of ferroptosis-related genes (FRGs) as prognostic biomarkers for cervical cancer patients is essential. Methods: In this study, 52 FRGs were obtained from the GSE9750, GSE7410, GSE63514, and FerrDb databases. Six genes possessing prognostic characteristics were identified: JUN, TSC22D3, SLC11A2, DDIT4, DUOX1, and HELLS. The multivariate Cox regression analysis was employed to establish and validate the prognostic model, while simultaneously performing a correlation analysis of the immune microenvironment. Results: The prediction model was validated using TCGA-CESC and GSE44001 datasets. Furthermore, the prognostic model was validated in endometrial cancer and ovarian serous cystadenocarcinoma cases. KM curves revealed significant differences in OS between high-risk and low-risk groups. ROC curves demonstrated the stability and accuracy of the prognostic model established in this study. Concurrently, the research identified a higher proportion of immune cells in patients within the low-risk group. Additionally, the expression of immune checkpoints (TIGIT, CTLA4, BTLA, CD27, and CD28) was elevated in the low-risk group. Ultimately, 4 FRGs in cervical cancer were corroborated through qRT-PCR. Conclusion: The FRGs prognostic model for cervical cancer not only exhibits robust stability and accuracy in predicting the prognosis of cervical cancer patients but also demonstrates considerable prognostic value in other gynecological tumors.

Recombinant human erythropoietin accelerated the proliferation of non-small cell lung cancer cell lines and reduced the expression of VEGF, HIF-1α, and PD-L1 under a simulated hypoxic environment in vitro.

Background: As erythropoietin (EPO) has been used to treat anemia in cancer patients, negative controversy has continued. Unfortunately, its effects on non-small-cell lung carcinoma (NSCLC) cell lines are uncertain and the phenomenon of inducing immune escape of tumor cells remains to be explored. This study aimed to provide an important basis for the application of exogenous EPO in the treatment of tumor-associated anemia. Methods: Cells were cultured in 1% O2, 5% CO2, and 94% N2 to simulate a hypoxic environment of the tumor. A549 cell line (lower expression EPOR) and NCI-H838 cell line (higher expression EPOR) were treated with 2 and 8 U/ml recombinant human EPO (rhEPO). CCK-8 method was used to determine the logarithmic growth phase of the cells and to detect cell proliferation. The expression levels of VEGF, HIF-1α, and PD-L1 were determined by western blot. One-way ANOVA was used for statistical analysis between groups, with p < 0.05 indicating a significant difference. Results: Hypoxia itself could decrease the survival rate of NSCLC cells. Under the hypoxic condition, rhEPO induced tumor cells proliferation, especially in the NCI-H838 cell line, where 2 U/ml rhEPO increased the total number of surviving cells (Hypoxia + rhEPO 2 U/ml vs. Hypoxia, p < 0.05). Western blot analysis showed that hypoxia upregulated the expression of VEGF, HIF-1α, and PD-L1 in NSCLC cell lines (Normoxia vs. Hypoxia, p < 0.05), but may not be dependent on the expression levels of EPOR. RhEPO decreased the expression levels of VEGF and HIF-1α. In the A549 cell line, it depended on the concentration of rhEPO and was particularly obvious in HIF-1α (Hypoxia vs. Hypoxia + rhEPO 2 U/ml vs. Hypoxia + rhEPO 8 U/ml, p < 0.05). A low concentration of rhEPO may not reduce VEGF expression. In the NCI-H838 cell line, the effect of rhEPO on VEGF was more obvious, but it may be independent of rhEPO concentrations. The downregulation of PD-L1 expression by rhEPO was only presented in the A549 cell line and required higher rhEPO concentrations (Hypoxia + rhEPO 8 U/ml vs. Hypoxia&Hypoxia + rhEPO 2 U/ml, p < 0.05). Conclusion: The effect of prolonged high concentrations of rhEPO under hypoxic conditions resulted in accelerated cells proliferation of non-small-cell lung cancer and was independent of EPOR expression levels on the cell lines surface. Hypoxia resulted in increased expression of VEGF, HIF-1α, and PD-L1 on the NSCLC cell lines. Under normoxic conditions, rhEPO did not affect the expression of VEGF, HIF-1α, and PD-L1; but under hypoxic conditions, the application of rhEPO reduced the expression of VEGF, HIF-1α, and PD-L1, producing an impact on the biological behavior of tumor cells.

Pan-Cancer Analysis Based on EPOR Expression With Potential Value in Prognosis and Tumor Immunity in 33 Tumors.

Background: Erythropoietin receptor (EPOR), a member of the cytokine class I receptor family, mediates erythropoietin (EPO)-induced erythroblast proliferation and differentiation, but its significance goes beyond that. The expression and prognosis of EPOR in cancer remain unclear. Methods: This study intended to perform a pan-cancer analysis of EPOR by bioinformatics methods. Several databases such as GTEx, TCGA, CCLE, and others were used to explore the overall situation of EPOR expression, and the correlation of EPOR expression with prognosis, microRNAs (miRNAs), immune infiltration, tumor microenvironment, immune checkpoint genes, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), methyltransferases, and DNA mismatch repair (MMR) genes in 33 tumors was analyzed. In addition, we compared the promoter methylation levels of EPOR in cancer tissues with those in normal tissues and performed protein-protein interaction network, gene-disease network, and genetic alteration analyses of EPOR, and finally enrichment analysis of EPOR-interacting proteins, co-expressed genes, and differentially expressed genes. Results: The TCGA database showed that EPOR expression was upregulated in BLCA, CHOL, HNSC, KIRC, LIHC, STAD, and THCA and downregulated in LUAD and LUSC. After combining the GTEx database, EPOR expression was found to be downregulated in 18 cancer tissues and upregulated in 6 cancer tissues. The CCLE database showed that EPOR expression was highest in LAML cell lines and lowest in HNSC cell lines. Survival analysis showed that high EPOR expression was positively correlated with OS in LUAD and PAAD and negatively correlated with OS in COAD, KIRC, and MESO. Moreover, EPOR had a good prognostic ability for COAD, LUAD, MESO, and PAAD and also influenced progression-free survival, disease-specific survival, disease-free survival, and progression-free interval in specific tumors. Further, EPOR was found to play a non-negligible role in tumor immunity, and a correlation of EPOR with miRNAs, TMB, MSI, and MMR genes and methyltransferases was confirmed to some extent. In addition, the enrichment analysis revealed that EPOR is involved in multiple cancer-related pathways. Conclusion: The general situation of EPOR expression in cancer provided a valuable clinical reference. EPOR may be target gene of hsa-miR-575, etc. A pan-cancer analysis of panoramic schema revealed that EPOR not only may play an important role in mediating EPO-induced erythroblast proliferation and differentiation but also has potential value in tumor immunity and is expected to be a prognostic marker for specific cancers.

The effect of near-surface electron trapping layer on the acetone sensing performance of black TiO2capped with ZnO.

In recent years, high-performance acetone gas sensors have attracted great attention for their potential in noninvasive blood glucose monitoring. In this work, black TiO2(B-TiO2) was introduced as an electron trapping layer between TiO2and ZnO to form TiO2@B-TiO2@ZnO core-shell nanoparticles, through a simple and safe method. The acetone sensing performance of TiO2@B-TiO2@ZnO varied with the thickness of ZnO. Because of the electron trapping effect of the introduced B-TiO2layer, the best performing sample exhibited a low optimal operating temperature of 275 °C and a high response of 49.25-50 ppm acetone. In addition, a low detection limit of 170 ppb was obtained. The pretty selectivity of the sample was also been proved. The mechanism of enhanced acetone response was explained by the energy band-based model of TiO2@B-TiO2@ZnO core-shell nanoparticle and depletion layer theory.

Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma.

OBJECTIVE: Lymphocyte cytosolic protein 2 (LCP2) is often ectopically expressed in various human tumors. However, the clinical significance and role of LCP2 in lung adenocarcinoma (LUAD) remain unclear. This study explored the prognostic significance of LCP2 in LUAD patients. METHODS: LCP2 expression in LUAD tissues was analyzed using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Western blotting was employed to detect LCP2 expression in LUAD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore signaling pathways mediated by LCP2 co-regulatory genes. Immunohistochemistry was used to examine levels of LCP2 and programmed death ligand 1 (PD-L1) in 68 LUAD patients. Associations between LCP2 expression and clinicopathological features, prognoses, and PD-L1 levels among the LUAD in-patients were analyzed. RESULTS: Among the 68 LUAD in-patients, LCP2 expression was correlated with clinical stage and lymph node metastasis. LUAD patients with high LCP2 expression were associated with increased overall survival. LCP2 expression may be associated with an enrichment of several immune functions. Moreover, our immunohistochemistry results demonstrated that LCP2 expression was positively correlated with PD-L1 expression in LUAD tissues. CONCLUSIONS: In the study, LCP2 was found to be a favorable prognostic biomarker in LUAD patients.

The value of complete blood count for the prognosis analysis of preoperative esophageal squamous cell carcinoma.

OBJECTIVE: To investigate the predictive value of preoperative complete blood count for the survival of patients with esophageal squamous cell carcinoma. METHODS: A total of 1587 patients with pathologically confirmed esophageal squamous cell carcinoma who underwent esophagectomy in the Cancer Hospital Affiliated to Xinjiang Medical University from January 2010 to December 2019 were collected by retrospective study. A total of 359 patients were as the validation cohort from January 2015 to December 2016, and the remaining 1228 patients were as the training cohort. The relevant clinical data were collected by the medical record system, and the patients were followed up by the hospital medical record follow-up system. The follow-up outcome was patient death. The survival time of all patients was obtained. The Cox proportional hazards regression model and nomogram were established to predict the survival prognosis of esophageal squamous cell carcinoma by the index, their cut-off values obtained the training cohort by the ROC curve. The Kaplan-Meier survival curve was established to express the overall survival rate. The 3-year and 5-year calibration curves and C-index were used to determine the accuracy and discrimination of the prognostic model. The decision curve analysis was used to predict the potential of clinical application. Finally, the validation cohort was used to verify the results of the training cohort. RESULTS: The cut-off values of NLR, NMR, LMR, RDW and PDW in complete blood count of the training cohort were 3.29, 12.77, 2.95, 15.05 and 13.65%, respectively. All indicators were divided into high and low groups according to cut-off values. Univariate Cox regression analysis model showed that age (≥ 60), NLR (≥3.29), LMR (< 2.95), RDW (≥15.05%) and PDW (≥13.65%) were risk factors for the prognosis of esophageal squamous cell carcinoma; multivariate Cox regression analysis model showed that age (≥ 60), NLR (≥3.29) and LMR (< 2.95) were independent risk factors for esophageal squamous cell carcinoma. Kaplan-Meier curve indicated that age <  60, NLR < 3.52 and LMR ≥ 2.95 groups had higher overall survival (p <  0.05). The 3-year calibration curve indicated that its predictive probability overestimate the actual probability. 5-year calibration curve indicated that its predictive probability was consistent with the actual probability. 5 c-index was 0.730 and 0.737, respectively, indicating that the prognostic model had high accuracy and discrimination. The decision curve analysis indicated good potential for clinical application. The validation cohort also proved the validity of the prognostic model. CONCLUSION: NLR and LMR results in complete blood count results can be used to predict the survival prognosis of patients with preoperative esophageal squamous cell carcinoma.

The correlation between tumor-associated macrophage infiltration and progression in cervical carcinoma.

Tumor microenvironment (TME) plays a particularly important role in the progression, invasion and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of the tumor microenvironment in CC. However, the results of studies on the correlation between TAMs and progression in CC are still controversial. This research aimed to investigate the relationship between TAMs infiltration and progression in CC. A total of 100 patients with CC were included in the study. The correlation between TAMs and clinicopathologic features was studied. Besides, a systematic literature search was conducted from legitimate electronic databases to specifically evaluate the role of TAMs in TME of cervical carcinoma. In the meta-analysis, high stromal CD68+ TAMs density was relevant to lymph node metastasis (WMD = 11.89, 95% CI: 5.30-18.47). At the same time, CD163+ M2 TAM density was associated with lymph node metastasis (OR = 2.42, 95% CI: 1.09-5.37; WMD = 39.37, 95% CI: 28.25-50.49) and FIGO stage (WMD = -33.60, 95% CI: -45.04 to -22.16). This was further confirmed in the experimental study of 100 tissues of cervical cancer. It supported a critical role of TAMs as a prospective predictor of cervical cancer. In conclusion, CD68+ TAM and CD163+ M2 TAM infiltration in CC were associated with tumor progression. And CD163+ M2 TAM infiltration was associated with more advanced FIGO stage and lymph node metastasis in CC.

Clinical Value of SARS-CoV2 IgM and IgG Antibodies in Diagnosis of COVID-19 in Suspected Cases.

OBJECTIVE: To explore the clinical value of SARS-CoV2 IgM and IgG antibodies in the diagnosis of COVID-19 in suspected cases by likelihood ratio. METHODS: By reinterpreting data from a previous study, the positive likelihood ratio of IgM and IgG antibodies in COVID-19 pneumonia diagnosis was calculated, and the posterior probability of IgM and IgG antibodies and their tandem detection was calculated finally. RESULTS: The positive likelihood ratios of single IgM and IgG antibodies were 18.50 and 12.65, respectively, and the posterior probabilities were 90.18% and 86.26%, respectively. However, the posterior probability of the two antibody-tandem test was 99.15%, which could give clinicians more quantitative confidence in the diagnosis of COVID-19 in suspected cases. According to the results of this study, combining the advantages and disadvantages of nucleic acid testing and antibody detection, a feasible clinical path was found for clinicians to diagnose COVID-19 pneumonia from suspected cases. CONCLUSION: For suspected cases, IgM- and IgG-antibody tests should first be done at the same time. If all antibody tests are positive, COVID-19 pneumonia could be confirmed. If not, nucleic acid detection (once or more) should be carried out, and in extreme cases high-throughput viral genome sequencing is required.

Comparison of double antigen sandwich and indirect enzyme-linked immunosorbent assay for the diagnosis of hepatitis C virus antibodies.

BACKGROUND: The aim of this study is to compare double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) and indirect ELISA in the diagnosis of hepatitis C virus（HCV）infection. METHODS AND MATERIALS: A total of 176 samples from the Tumor Hospital Affiliated to Xin Jiang Medical University were utilized to comparison. All serum samples were tested using double-antigen sandwich ELISA and indirect ELISA. Cohen's kappa statistics were used to assess the agreement between the two assays, and multivariate analysis was used to evaluate risk factors for the discordance between the double-antigen ELISA and indirect ELISA. RESULTS: The positivities of indirect ELISA (Beijing Wantai), double-antigen sandwich ELISA (Beijing Wantai), and indirect ELISA (Beijing Jinhao) were 74.43%, 68.75%, and 73.30%, respectively. The agreement between the indirect ELISA (Beijing Wantai) and double-antigen sandwich ELISA (Beijing Wantai) was high (κ = 0.829;P < .001), and the agreement between the double-antigen sandwich ELISA (Beijing Wantai) and indirect ELISA (Beijing Jinhao) was high (κ = 0.847;P < .001). Variables associated with discordant results between the double-antigen sandwich and indirect ELISA in multivariate analysis were as follows: female (OR:1.462; P < .05), age (<35 years old; OR:3.667; P < .05), and cancer (suffer from malignant tumor; OR:3.621; P < .05). CONCLUSION: In detection of HCV, high agreement was found between the double-antigen sandwich ELISA and indirect ELISA. Female, younger age, and suffer from malignant tumor were significant risk factors for the discordance. Based on double-antigen sandwich ELISA has distinct methodological advantages over indirect ELISA. It is recommended for the diagnosis of HCV infection.

Comprehensive Analysis of the Expression and Prognosis for MCMs in Human Gastric Cancer.

PURPOSES: Minichromosome maintenance (MCM) proteins play an important role in replication and cell cycle progression. Even so, their expression and prognostic roles in cancer remain controversial. METHODS: To address this issue, the study investigated the roles of MCMs in the prognosis of GC by using ONCOMINE, GEPIA2, UALCAN, Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, and DAVID databases. RESULTS: Over expressions of mRNA and cell lines were found in all members of the MCM family, and MCMs were found to be significantly associated with pathological tumor grades in GC patients. Besides, higher mRNA expressions of MCM1/5/7 were found to be significantly associated with shorter overall survival (OS) and progression-free survival (FP) in GC patients, while higher mRNA expression of MCM4/6/9 were connected with favorable OS and FP. Moreover, a high mutation rate of MCMs (68%) was also observed in GC patients. CONCLUSIONS: The results indicated that MCM1/5/7 were potential targets of precision therapy for patients with GC. And MCM4/6/9 were new biomarkers for the prognosis of GC. The results of the study will contribute to supplement the existing knowledge, and help to explore therapeutic targets and enhance the accuracy of prognosis for patients with GC.

Tumor-Associated CD163+ M2 Macrophage Infiltration is Highly Associated with PD-L1 Expression in Cervical Cancer.

BACKGROUND: Programmed death-ligand 1 (PD-L1) is a negative costimulatory molecule, and its main function is widely considered to be in the regulation of T cells. Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosuppression. However, the relationship between the expression of PD-L1 and TAMs in cervical carcinoma (CC) remains unclear. We detected the expression of PD-L1 and TAMs in tumor tissue to study the correlation between them. METHODS: Immunohistochemical staining of PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) was performed in 120 cases of cervical squamous cell carcinoma. Logistic regression analysis was used to evaluate the predictors related to positive PD-L1 expression. We also apply the Kaplan-Meier method to study the recurrence-free and overall survival rate of CC patients. RESULTS: The increase in PD-L1 expression in tumor cells (TC) was significantly correlated with the increase in CD163 density (r=0.8550, p<0.0001), while PD-L1 in the stroma was also significantly associated with the intratumoral density of CD68- or CD163-positive cells (CD68 p<0.0001; CD163 p=0.0009). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive TC were significantly higher than in PD-L1-negative TC (CD68 p=0.0095; CD163 p<0.0001). In multivariate logistic regression analyses, only the density of CD163-positive cells was correlated with the expression of PD-L1 in TC cells (OR 1.52; p=0.032). In prognostic analysis, PD-L1 more than 10% was significantly correlated with short RFS (HR=2.66; p=0.028). For CD163+ macrophage evaluation, the density above the median was also significantly correlated with RFS (HR=2.48; p=0.021). CONCLUSION: CD163+ M2-like macrophage infiltration is highly associated with PD-L1 expression in CC, suggesting that macrophage infiltration can serve as a potential therapeutic target.

The Value of ABO Blood Group and Complete Blood Count for the Prognosis Analysis of Gastric Cancer Patients.

OBJECTIVE: To investigate the value of ABO blood group and complete blood count results in predicting the survival rate of patients with gastric cancer. PATIENTS AND METHODS: A retrospective study was conducted to collect 488 gastric cancer patients diagnosed in the Tumor Hospital Affiliated to Xinjiang Medical University from January 2010 to December 2011. Relevant clinical data were collected by the medical record system, and the patients were followed up by the medical record follow-up system of the hospital. The follow-up was ended until the death of the patients, and the survival time of all patients was obtained. Survival curve and Cox regression analysis model were used to study the role of various indicators in the prognosis of gastric cancer patients. RESULTS: Neutrophil lymphocyte ratio (NLR), neutrophil monocyte ratio (NMR), lymphocyte monocyte ratio (LMR) and platelet distribution width (PDW) in blood routine test could predict the death outcome of gastric cancer patients, with the predicted thresholds of 1.95, 13.49, 5.22 and 11.25, respectively. Survival curve analysis showed that female patients, type O blood patients, LMR >5.22 patients, NMR >13.49 patients and NLR ≤1.95 patients had longer survival. Multivariate Cox regression analysis model showed that gender and NLR were independent prognosis risk factors for gastric cancer, with HR values of 2.964 (95% CI of 2.258-3.891) and 1.103 (95% CI of 1.028-1.183), respectively. PLT and PDW were independent prognosis protective factors for gastric cancer, with HR values of 0.998 (95% CI of 0.997-1.000) and 0.891 (95% CI of 0.797-0.996), respectively. Compared with type O blood patients, patients with type A blood, type B blood and type AB blood had 3.472 times (95% CI 2.562-4.706), 3.368 times (95% CI 2.454-4.624) and 4.407 times (95% CI 2.871-6.766) increased risk of death. CONCLUSION: The results of NLR, PLT, PDW and ABO blood group can help to predict the survival of gastric cancer patients.

Optimize Clinical Laboratory Diagnosis of COVID-19 from Suspect Cases by Likelihood Ratio of SARS-CoV-2 IgM and IgG antibody

ObjectiveTo optimize clinical laboratory diagnosis of COVID-19 from suspect cases by Likelihood Ratio of SARS-CoV-2 IgM and IgG antibody. MethodsBy reinterpreting the data in the article "Diagnostic Value of Combined Detection of Serum 2019 novel coronavirus IgM and IgG Antibodies in novel coronavirusin Infection", the positive likelihood ratio of IgM and IgG antibody in diagnosis of COVID-19 (nucleic acid positive patients) was calculated, and the posterior probability of IgM and IgG antibodies and their tandem detection to diagnose was finally calculated. ResultsThe positive likelihood ratios of single IgM and IgG antibody were 18.50 and 12.65 respectively, and the posterior probabilities were 90.18% and 86.26% respectively. However, the posterior probability of the two antibodies tandem detection is 99.15%, which can give clinicians quantitative confidence in the diagnosis of COVID-19 from suspected cases. According to the results of this study, combining the advantages and disadvantages of nucleic acid detection and antibody detection, the clinical pathway for clinicians to diagnose COVID-19 is found. ConclusionFor suspected cases, IgM and IgG antibody tests should be firstly done at the same time. If the antibody tests are all positive, COVID-19 can be confirmed. If not, nucleic acid detection (one or more times) is performed, and in extreme cases, high-throughput viral genome sequencing is performed.

The Leukocyte VCS Parameters Compared with Procalcitonin, Interleukin-6, and Soluble Hemoglobin Scavenger Receptor sCD163 for Prediction of Sepsis in Patients with Cirrhosis.

BACKGROUND: Patients with liver cirrhosis have a high risk of sepsis and a poor prognosis. Recently, a new standard for sepsis (Sepsis-3) has been proposed in the general population. The Coulter Lh 750 hematology analyzer can evaluate mean volume, conductivity, scatter, and distribution width of leukocyte. We tried to use Sepsis-3 criteria to study the diagnostic value of volume, conductivity, and scattering (VCS) parameters in sepsis and infection in patients with liver cirrhosis compared with traditional infection markers (PCT, IL-6, sCDl63). METHODS: A blinded, cohort study was conducted in three different ED populations within three affiliated hospitals. A total of 249 patients with liver cirrhosis were enrolled in the study. According to the "Sepsis-3" consensus criteria, clinical history, and laboratory examination, the subjects were divided into sepsis (n = 54), patients with infections (n = 95), and patients without systemic infections (n = 100). The blood samples of the patients were collected at the time of ED admission and were evaluated for the detection of sepsis. RESULTS: The differences of MNV, MNS, MMV, MMS, MLV, NDW, and MDW in the three groups were statistically significant. In the diagnosis of sepsis in patients with liver cirrhosis, the sensitivity of combined detection of MMV and MDW was 88.89%; the specificity was 74%. This sensitivity was significantly better than the 83.3% achieved using 0.97 mg/L as the cutoff for sCD163. In the diagnosis of infection in cirrhosis, the sensitivity of combination of MNV and MMS was increased to 86.32%; the specificity was 92%. The sensitivity was the same as that achieved by using 0.31 ng/mL as the cutoff value of PCT, but the specificity increased. CONCLUSION: The leukocyte VCS parameter could be potential parameters for indicating sepsis and infection in patients with liver cirrhosis. The combined detection of MMV and MDW seemed to be helpful for the diagnosis of sepsis in these patients, and the combination of MNV and MMS could better indicate infection for them.