VEGF single nucleotide polymorphisms predict improved outcome in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy

Abstract

We aimed to investigate the prognostic role of genetic variants of VEGF in advanced NSCLC patients treated with platinum-based chemotherapy. A total of 196 patients with advanced NSCLC treated with first-line platinum-based chemotherapy were enrolled. We evaluated the relationship between VEGF polymorphisms and efficacy outcomes and chemotherapy toxicity. We found that rs699947, rs833061 and rs1005230 were in full linkage disequilibrium. Patients with CC genotype of rs833061 had a significant longer PFS than TT genotype (CC vs TT, HR = 1.67, 95%CI = 1.01−2.76, P = 0.043). Patients harbouring CC genotype had longer PFS compared with CT genotype (P < 0.001). Moreover, CC genotypes conferred a significantly increased PFS compared to CT and TT genotype in dominant model (CC vs CT + TT, HR = 1.95, 95%CI = 1.23−3.10, P = 0.005). Patients carrying TT genotype of rs833061 had improved both ORR (HR = 0.54, 95%CI = 0.30−0.98, P = 0.041) and DCR (HR = 0.37, 95%CI = 0.20−0.66, P = 0.001) than non-TT patients. Furthermore, no association was found between any rs833061 alleles and adverse events (P = 0.425), but patients carrying rs1570360 AA genotype were more likely to experience grade 3−4 toxicities (P = 0.004) (GG vs AA, HR = 3.16, 95%CI = 1.26−7.94, P = 0.015). In conclusion, the variant homozygote CC of rs833061 exhibited a better prognosis based on association analysis. The present study provides reference for the future study of platinum-based chemotherapy response and toxicity.

Keywords:

• Gene polymorphism
• NSCLC
• chemotherapy toxicity
• clinical outcome
• VEGF

Disclosure statement

The authors declare that they have no competing interests.

Statement of ethics

We declare all the contents of this study are strictly performed in accordance with the Declaration of Helsinki. The procedures of this study were approved by the Huashan Hospital Institutional Review Board and the approved number of ethic committee was 2017–011. All participants were aware of the content of the study and signed an informed consent.

Author contributions

LQY, QHJ and ZQ designed the study. ZWX and WY did genotyping and genetic analyses. QHJ, ZWX and WY drafted the manuscript. GMX and ZQ collected blood samples. WTX and ZLD collected and analyzed clinical data. ZMK, LXH and SXJ participated in its design and reviewed the manuscript. All authors discussed the results and implications of the manuscript and approved the final version to be published.

Data availability statement

The data generated and analyzed during the current study are not publicly available due confidentiality requirements, but are available from the corresponding author on reasonable request.

Additional information

Funding

The work was supported by the National Natural Science Foundation of China to QL (81973399) and to TW (81901399), the Shanghai ‘Rising Stars of Medical Talent’ Youth Development Program to QL (Youth Medical Talents-Clinical Pharmacist Program), the Research Foundation of Huashan Hospital North to HQ (2015107), Shanghai Key Clinical Specialty Projects-Clinical Pharmacy to MZ(shslczdzk06502), Scientific Research Project of Shanghai Health and Family Planning Commission to LZ (20184Y0194), and Clinical pharmacy management committee of Shanghai Hospital Association to XS (YS2021015).