Dataset Information

Genetic variants of BCL2 gene predict clinical outcomes of non-small-cell lung cancer patients treated with platinum-based chemotherapy in a Chinese population.

ABSTRACT: Platinum agents induce cancer cell death through BCL2-dependent intrinsic apoptotic pathway and are commonly used as anti-tumor drug. In this study, we evaluated whether single nucleotide polymorphism (SNPs) of BCL2 can affect the overall survival (OS) and progression-free survival (PFS) in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. We genotyped 48 SNPs of BCL2 gene by Illumina Custom Designed Chip in 972 advanced NSCLC patients treated with platinum-based chemotherapy. We evaluated the relationship between genotype/haplotype/diplotype and OS/PFS by COX regression analysis. As a result, five SNPs, rs949037, rs3810027, rs4987739, rs4987726 and rs7226979, were significantly associated with overall survival time in 972 NSCLC patients after platinum-based chemotherapy. rs1381547 and rs8083946 were associated with progression-free survival. As representative, the G allele of rs949037 was associated with longer OS in NSCLC patients with platinum-based chemotherapy. Patients with GG or AG genotype showed a 19.9 months mOS vs AA genotype 14.2 months mOS (HR: 1.38, 95% CI: 1.11-1.72, p=0.004). In further analysis, rs949037 was found to predominantly contribute to the OS of patients with platinum-tubulin-targeting drugs, moreover, the GG genotype of rs949037 showed an 8.5 months longer OS compared with the unfavorable AA genotype (mOS: 21.36 vs 12.83, HR=0.70, 95% CI: 0.52-0.94, p=0.000). To conclude, polymorphisms of BCL2 gene may have an impact on the OS of platinum-based chemotherapy in NSCLC patients, which may be prognostic biomarkers of chemotherapy if validated in larger studies.

SUBMITTER: Ding X

PROVIDER: S-EPMC5088294 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic variants of <i>BCL2</i> gene predict clinical outcomes of non-small-cell lung cancer patients treated with platinum-based chemotherapy in a Chinese population.

Ding Xi X Qian Ji J Yang Yang Y Xu Wen W Liu Di D Su Bo B

American journal of cancer research 20161001 10

Platinum agents induce cancer cell death through BCL2-dependent intrinsic apoptotic pathway and are commonly used as anti-tumor drug. In this study, we evaluated whether single nucleotide polymorphism (SNPs) of BCL2 can affect the overall survival (OS) and progression-free survival (PFS) in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. We genotyped 48 SNPs of BCL2 gene by Illumina Custom Designed Chip in 972 advanced NSCLC patients treated with platinum-ba ...[more]

PMID: 27822420

Similar Datasets

Project description:Background Platinum-based chemotherapy (PC) and immunotherapy plus platinum-based chemotherapy (IPC) remain the first-line treatment for advanced NSCLC. But only a minority patients benefit from PC, and existing biomarkers, such as PD-L1, have been shown to be defective in predicting the efficacy of IPC. Highlighting the need to identify novel biomarkers for the efficacy of PC and IPC. DNA damage repair (DDR) mutations are known to predict response to PC in solid tumors. However, the predictive value of DDR in PC and IPC of NSCLC remains unclear. Methods Patients diagnosed with advanced or metastatic NSCLC were retrospectively included if they underwent next generation sequencing prior to starting treatment. Primary endpoints were to explore whether DDR mutations (DDRmut) are associated with clinical outcomes of PC and IPC. Secondary end point were to explore the association between DDRmut and the choice to add immunotherapy to chemotherapy, and the impact of different DDR pathways on efficacy in PC and IPC. Results DDRmut showed a strong association with tumor mutation burden-high (TMB-H) versus DDR wild-type (DDRwt) and higher rates of PD-L1 TPS ≥50% positivity. In 63 patients treated with PC, ORRs were 15.38% and 2.86% for DDRmut and DDRwt subgroup (P=0.1536), and DCRs were 88.46% and 45.72% (P=0.00097) at 6 months after PC. The DDRmut patients had significantly improved median PFS (mPFS) and median overall survival (mOS) than DDRwt group (mPFS: 7.6 vs. 3.9 months, HR =1.93, 95% CI: 1.09 to 3.14, P=0.0220. mOS: 29.9 vs. 20.7 months, HR =2.31, 95% CI: 1.09 to 4.9, P=0.0250). Moreover, among 37 patients treated with IPC, ORRs were 45% and 11.76% for DDRmut and DDRwt patients (P=0.0365), and the DCRs were 95% and 70.58% (P=0.0752), respectively at 6 months after IPC. The DDRmut patients had significantly improved mPFS compared to the DDRwt group (19.5 vs. 4.5 months, HR =3.28, 95% CI: 1.53 to 9.56, P=0.0022). In DDRmut group, mPFS of IPC recipients was significantly better than that of PC recipients (19.5 vs. 7.6 months, HR =2.09, 95% CI: 0.98 to 4.42, P=0.050). Conclusions There is potential for DDR to serve as a positive predictor of PC and IPC in advanced NSCLC patients.

Dataset Information

Genetic variants of BCL2 gene predict clinical outcomes of non-small-cell lung cancer patients treated with platinum-based chemotherapy in a Chinese population.

Publications

Genetic variants of <i>BCL2</i> gene predict clinical outcomes of non-small-cell lung cancer patients treated with platinum-based chemotherapy in a Chinese population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets