The aim of this study was to investigate the usefulness of a novel inflammation-based prognostic system, called COP-LMR (combination of platelet count and lymphocyte to monocyte ratio), for predicting postoperative survival of patients with non-small cell lung cancer (NSCLC). COP-LMR was calculated on the basis of the obtained data. Patients with both an elevated platelet count (PLT) (>30 × 104mm-3) and a low LMR (<3.6) were assigned a score of 2, and patients with one or none of the parameters were assigned a score of 1 or 0, respectively. A total of 1120 patients who underwent complete resection were enrolled in this study. Multivariate analysis revealed that COP-LMR is an independent prognostic factor for disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001). Kaplan-Meier analysis and the log-rank test revealed that COP-LMR stratified the patients into 3 independent groups (P<0.001). In conclusion, COP-LMR is a potential prognostic biomarker in patients undergoing surgery for NSCLC.

Our results suggest that this polymorphism of ERCC1 at codon 118 is associated with patient response to cisplatin-based chemotherapy in treatments of late-stage NSCLC. Moreover, by assaying this SNP in blood cells, the ERCC1 codon 118 may represent a valuable biomarker in developing individualized treatments for NSCLC patients.

Breast cancer (BC) is one of the most common malignant tumors in women, and screening relevant genes and markers that are involved in BC tumor genesis and progression is of great value. We previously found that messenger RNA expression of ARHGAP9 was high in BC tissue, but it is unclear whether ARHGAP9 participates in the progression of human BC. In this study, we found that ARHGAP9 expression was correlated with poor patient survival, American Joint Committee on Cancer clinical staging, tumor size, and tumor differentiation. MCF-7 and MDA-MB-231 cells exhibited higher expression of ARHGAP9 than other human BC cell lines (HCC1937, MDA-MB-453, ZR-75-1, and Hs 578T). Knockdown of ARHGAP9 in human BC cells markedly reduced the cell proliferation, migration, and invasive ability of MCF-7 and MDA-MB-231 cells. Furthermore, small interfering RNA (siRNA) of ARHGAP9 also induced G0-G1 cell cycle arrest and apoptosis in MCF-7 and MDA-MB-231 cells. Expressions of cell cycle markers (CDK2 and CCNB1) and invasion-related protein (RhoC and MTA1) were downregulated in siRNA-ARHGAP9-transfected cells. siRNA of ARHGAP9 also inhibited the phosphorylation of mitogen-activated protein kinases in BC cells. In conclusion, the abnormal expression of ARHGAP9 may correlate with the genesis, development, and diagnosis of BC.

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BackgroundThymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response. This study investigated the expressions of TS and its gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected NSCLC specimens and corresponding normal tissues to assess the expressions of TS protein and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung adenocarcinoma patients were examined for polymorphisms of the TS gene 3’-UTR 1494del 6 bp, which was then investigated for associations with responses of the patients to pemetrexed treatment and survival.ResultsExpression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma. TS expression was associated with poor tumor differentiation. Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the TS gene 3’-UTR 1494 bp (−6 bp/-6 bp) genotype and the rest had TS gene 3’-UTR 1494 bp (−6 bp/+6 bp). There was no TS 3’-UTR 1494 bp (+6 bp/+6 bp) genotype in any patients. Statistical analysis revealed that gender, tumor stage, and TS 3’-UTR 1494del 6 bp polymorphism were significant prognostic factors after short-term pemetrexed treatment. Log-rank analysis revealed that patients with the (−6 bp/-6 bp) genotype had significantly better progression-free and overall survival than patients with (−6 bp/+6 bp).ConclusionsThis study showed that TS protein is highly expressed in NSCLC and that polymorphisms of TS 3’-UTR 1494del 6 bp are associated with sensitivity of lung adenocarcinoma patients to pemetrexed treatment. This suggests that TS gene polymorphisms should be further evaluated as prognostic markers for personalized therapy in lung adenocarcinoma.