Mechanism of Hirudin-Mediated Inhibition of Proliferation in Ovarian Cancer Cells.

To investigate the inhibitory effect of hirudin on the cell proliferation of human ovarian cancer A2780 cells by preventing thrombin and its underlying molecular mechanism. Cell Counting Kit-8 (CCK-8) method was used to detect the effect of different concentrations of hirudin and thrombin on the cell proliferation of A2780 cells. PAR-1 wild-type overexpression plasmid was constructed utilizing enzyme digestion identification, and it was transferred to A2780 cells. Sequencing and Western blot were used to detect the changes in PAR-1 protein expression. Western blot detection of PKCα protein phosphorylation in A2780 cells was performed. We also implemented quantitative PCR to detect the mRNA expression levels of epithelial-mesenchymal transition (EMT)-related genes, CDH2, Snail, and Vimentin, in A2780 cells. 1 µg/ml hirudin treatment maximally inhibited the promotion of A2780 cell proliferation by thrombin. Hirudin inhibited the binding of thrombin to the N-terminus of PAR-1, hindered PKCα protein phosphorylation in A2780 cells, and downregulated the mRNA expression levels of CDH2, Snail, and Vimentin. In conclusion, hirudin inhibits the cell proliferation of ovarian cancer A2780 cells, and the underlying mechanism may be through downregulating the transcription level of EMT genes, CDH2, Snail, and Vimentin. This study indicates that hirudin may have a therapeutic potential as an anti-cancer agent for ovarian cancer.

Systemic immune-inflammation index predicts prognosis and responsiveness to immunotherapy in cancer patients: a systematic review and meta­analysis.

The systemic immune-inflammation index (SII) is a significant prognostic factor in some cancer types. However, the prognostic role of SII in cancer patients with immunotherapy remains uncertain. We aimed to evaluate the relationship between pretreatment SII and clinical survival outcomes for advanced-stage cancer patients treated with immune checkpoint inhibitors (ICIs). A comprehensive literature search was performed to identify eligible studies concerning the association between pretreatment SII and survival outcomes in advanced cancer patients treated with ICIs. The data were extracted from publications and used to calculate the pooled odds ratio (pOR) for objective response rate (ORR), disease control rate (DCR), and pooled hazard ratio (pHR) for overall survival (OS), progressive-free survival (PFS), along with 95% confidence intervals (95% CIs). Fifteen articles with 2438 participants were included. A higher level of SII indicated a lower ORR (pOR = 0.73, 95% CI 0.56-0.94) and worse DCR (pOR = 0.56, 95% CI 0.35-0.88). High SII was associated with a shorter OS (pHR = 2.33, 95% CI 2.02-2.69) and unfavorable PFS (pHR = 1.85, 95% CI 1.61-2.14). Therefore, high SII level might be a non-invasive and efficacious biomarker of poor tumor response and adverse prognosis of advanced cancer patients with immunotherapy.

Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Objective: To investigate the association between pretreatment prognostic nutritional index (PNI) and clinical survival outcomes for advanced-stage cancer patients treated with immune checkpoint inhibitors (ICIs). Methods: We conducted a comprehensive literature search to identify eligible studies concerning the relationship between pretreatment PNI and survival outcomes in advanced cancer patients treated with ICIs. Published data were extracted and pooled odds ratio (pOR) for objective response rate (ORR), disease control rate (DCR), and pooled hazard ratio (pHR) for overall survival (OS), progressive-free survival (PFS), along with 95% confidence intervals (95% CIs) were calculated. Results: Twelve studies with 1,359 participants were included in our study. A higher level of PNI indicated a greater ORR (pOR = 2.17, 95% CI = 1.52-3.10) and favorable DCR (pOR = 2.48, 95% CI = 1.87-3.29). Low PNI was associated with a shorter OS (pHR = 2.24, 95% CI = 1.57-3.20) and unfavorable PFS (pHR = 1.61, 95% CI = 1.37-1.88). Conclusion: Low PNI might be an effective biomarker of poor tumor response and adverse prognosis of advanced cancer patients with ICIs. Further studies are needed to verify the prognostic value of PNI in clinical practice.

Associations between AGT M235T Polymorphism and Cancer: An Updated Meta-Analysis.

We assessed the relationship between AGT gene M235T polymorphism and the susceptibility to cancer by performing an updated meta-analysis. This study retrospectively searched related articles in the electronic databases. Afterwards, we determined combined odds ratios (ORs) and related 95% confidence intervals (CIs) by the fixed- or random-effects model. The present meta-analysis enrolled altogether 9 articles. On the whole, the relationship between AGT M235T polymorphism and the cancer risk was not significant among the entire population (TT vs. MM: OR = 1.28, 95%CI = 0.80 - 2.04; TM vs. MM: OR = 0.90, 95%CI = 0.53 - 1.52; recessive model: OR = 1.13, 95%CI = 0.83 - 1.52; dominant model: OR = 0.93, 95%CI = 0.55 - 1.57). Subgroup analysis by ethnicity, cancer type, and study quality for the relationship between the AGT M235T polymorphism and cancer risk showed no significant association. According to findings in the present meta-analysis, AGT M235T polymorphism may not be related to cancer susceptibility.

Association Studies of ERCC2 rs13181 Polymorphism with Pancreatic Cancer Susceptibility.

Although the ERCC2 gene rs13181 polymorphism is involved in the pancreatic cancer pathogenic mechanism, there is no consistent finding. This meta-analysis aimed to determine the association between ERCC2 rs13181 polymorphism and pancreatic cancer. Related articles were searched against the PubMed database in a retrospective way. Additionally, the combined odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated using the random- or fixed-effects model. Altogether, seven articles regarding ERCC2 gene rs13181 polymorphism were enrolled. The combined ORs regarding the relationship of ERCC2 rs13181 polymorphism with pancreatic cancer incidence showed significant differences in each genetic model (C vs. A: OR = 1.14, 95% CI = 1.04-1.26; CC vs. AA: OR = 1.53, 95% CI = 1.24-1.90; AC vs. AA: OR = 1.06, 95% CI 0.92-1.22; recessive model: OR = 1.50, 95% CI = 1.22-1.84; dominant model: OR = 1.16, 95% CI = 1.02-1.32). Additionally, we performed subgroup analysis stratified by race, which revealed that ERCC2 rs13181 polymorphism increased the risk of pancreatic cancer in Asian populations. This work suggests that the ERCC2 gene rs13181 polymorphism is related to pancreatic cancer risk in Asians.

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population.

OBJECTIVE: The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C677T excision repair cross-complementation group 1 (ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC). METHODS: A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 C118T were genotyped using the TaqMan methods. RESULTS: The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype (TT or CT) (41.2% versus 19.1%, P=0.01). Median time to progression (TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype (7.6 months versus 5.0 months, P=0.003). No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. CONCLUSIONS: Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

The T393C polymorphism of GNAS1 as a predictor for chemotherapy sensitivity and survival in advanced non-small-cell lung cancer patients treated with gemcitabine plus platinum.

PURPOSE: The GNAS1 gene is linked to proapoptotic signaling and correlates closely with clinical outcomes in many human cancers. The aim of this study was to evaluate whether the T393C polymorphism of the GNAS1 gene could be used as a chemotherapy sensitivity and prognosis predictive marker of advanced non-small-cell lung cancer (NSCLC) treated with gemcitabine plus platinum (GP). METHODS: In this study, we performed the PCR-restriction fragment length polymorphism assay to examine the genotypes of the GNAS1 T393C polymorphism in 131 peripheral blood DNA specimens from advanced NSCLC patients with GP treatment. RESULTS: The frequencies of the CC, CT, and TT genotypes in 131 advanced NSCLC cases were 25.2, 47.4, and 26.7%, respectively. The favorable TT genotype was significantly correlated with better overall survival (OS; P < 0.05) and longer progress-free survival (PFS; P < 0.05) compared with the CT or CC genotype. In the multivariate Cox proportional hazards model, the GNAS1 T393C polymorphism was independently associated with overall survival after adjusting the clinicopathological factors (P < 0.05). CONCLUSIONS: This study suggests that the TT genotype of the GNAS1 T393C polymorphism could be an independent prognostic marker to predict chemotherapy sensitivity, favorable OS and PFS in advanced NSCLC patients with GP treatment.