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Association of HIF1-α gene polymorphisms with advanced non-small cell lung cancer prognosis in patients receiving radiation therapy.

ABSTRACT: We investigated the association between single nucleotide polymorphisms (SNPs) in the HIF1A gene and the prognosis of advanced non-small cell lung cancer (NSCLC) patients undergoing radiation therapy. Patient overall survival (OS) and progression-free survival (PFS) were analyzed. The rs11549465 TT genotype was associated with poor PFS (P<0.001) and OS (P=0.001). The rs2057482 TT genotype was also associated with poor PFS (P=0.002) and OS (P=0.007). Stratified analyses revealed that these associations occurred in patients with a smoking history, squamous cell carcinoma, and stage IIIA disease, as well as those receiving radiation therapy a radiation dose of ≥70 Gy. We found associations between SNPs and PFS but not OS in patients without a smoking history, other histological types, and stage IIIB disease, as well as those undergoing chemoradiotherapy with a radiation dose of <70 Gy. No associations were observed between rs11549467 or rs110873142 and NSCLC prognosis. These results suggest that HIF1A polymorphisms can be used as independent prognostic biomarkers for NSCLC patients receiving radiation therapy.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7993740 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundInflammation is not only involved in the development and progression of cancer but also affects the response to therapy. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in inflammation genes with the prognosis of advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).MethodsForty-seven SNPs were genotyped in 318 advanced NSCLC patients receiving EGFR-TKIs. Of 318 patients, 182 (57.2%) patients died during follow-up period. We assessed the association of SNPs with the progression-free survival (PFS) and overall survival (OS) as well as calculated the weighted genetic risk score (GRS). We also explored the expression levels and prognostic values of inflammation genes in lung adenocarcinoma (LUAD) in Gene Expression Profiling Interactive Analysis (GEPIA) and using UCSC Xena, respectively. The relationship between the expression levels of IL15, IL17RA, AGER, MIF, and TNFRSF1A and EGFR mutation status was analyzed using UCSC Xena.ResultsIn single variant analyses, 3 SNPs (rs10519613, rs4819554, and rs4149570) were significantly associated with worse PFS. Five SNPs (rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) were significantly with worse OS. In addition, high and intermediate GRSs (based on rs10519613, rs4819554, and rs4149570) were associated with worse PFS than those with low GRS. For OS, patients with high GRSs (based on rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) had shorter survival time than those with low GRS. Furthermore, IL15, IL17RA, AGER, MIF, and TNFRSF1A were dysregulated in LUAD. There was difference in the expression level of TNFRSF1A between EGFR wildtype and EGFR-mutant LUAD. Both low AGER expression and high TNFRSF1A expression were significantly associated with worse PFS in LUAD. In addition, low IL17RA and AGER expression, high MIF and TNFRSF1A expression were significantly associated with worse OS in LUAD.ConclusionSNPs in inflammation genes could serve as prognostic biomarkers for NSCLC patients treated with EGFR-TKIs.

Project description:BackgroundLung cancer is the leading cause of cancer-related deaths. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective for advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations, some patients experience little or no response. The Glasgow prognostic score (GPS) is an inflammation-related score based on C-reactive protein (CRP) and albumin concentrations, and has prognostic value in various cancer settings. This study aimed to evaluate whether GPS could predict response of NSCLC to EGFR-TKIs.MethodsThis retrospective multicenter study evaluated patients with NSCLC harboring EGFR mutations who received EGFR-TKI monotherapy from October 2006 to December 2016. GPS values were determined using CRP and albumin concentrations from before initiation of EGFR-TKIs. The Kaplan-Meier method and Cox proportional hazard models were used to evaluate progression-free survival (PFS) and overall survival (OS).ResultsIn 214 patients, 141, 43, and two patients had GPS values of 0, 1, and 2, respectively. The GPS independently predicted the efficacy of EGFR-TKIs; good GPS (0-1) conferred significantly better PFS (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.38-0.96, P = 0.03) and OS (HR: 0.56, 95% CI: 0.33-0.96, P = 0.03). Multivariate analysis confirmed that a good GPS (0-1) independently predicted good PFS and OS among patients who had PS of 0-1. Good GPS (0-1) independently predicted good OS among patients receiving treatment in first-line settings.ConclusionsThe GPS independently predicted the efficacy of EGFR-TKIs for EGFR-mutated NSCLC; however, further studies are needed to validate our findings.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: Glasgow prognostic score (GPS) independently predicted the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment for EGFR-mutated NSCLC.What this study addsThe findings presented in this paper will help to identify patients who will be expected to experience limited or no response to EGFR-TKI treatment by using GPS.

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Association of HIF1-α gene polymorphisms with advanced non-small cell lung cancer prognosis in patients receiving radiation therapy.

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