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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1459749
This article is part of the Research Topic Hepatocellular Carcinoma: Novel Treatment Strategies - Volume III View all 13 articles

Immune-checkpoint HLA-G gene polymorphisms, 3'-UTR types and their association with hepatocellular carcinoma and treatment response in Indian population

Provisionally accepted
Neeti Nadda Neeti Nadda Renu Yadav Renu Yadav Neelanjana Roy Neelanjana Roy Nita Singh Nita Singh SONU KUMAR SONU KUMAR Dr Shashi Paul Dr Shashi Paul Shivanand Gammanagatti Shivanand Gammanagatti Anoop Saraya Anoop Saraya . Shalimar . Shalimar Baibaswata Nayak Baibaswata Nayak *
  • All India Institute of Medical Sciences, New Delhi, India

The final, formatted version of the article will be published soon.

    Background: Human leukocyte antigen-G (HLA-G) is a cancer-associated immune checkpoint protein implicated in tumor-driven immune escape mechanisms. This study was undertaken to determine genetic variations at the 3'-UTR of the HLA-G gene that may alter its expression, identify risk alleles and genotypes for their association with hepatocellular carcinoma (HCC), and treatment responses in the Indian population.Methods: HCC cases (n = 100) and healthy controls (n = 110) were recruited for the genetic association study, of which 88 patients received LRT. Single nucleotide polymorphisms (SNPs) at the HLA-G 3'-UTR gene were genotyped by sequencing and PCR-RFLP. The genetic association of 14 SNPs with HCC and LRT responses was determined using population genetic approaches.Results: Three of the 14 SNPs (rs1707, rs1710, and rs1063320) were found to be genetically associated with HCC risk and treatment responses. These three UTR SNPs are important for miRNA binding. We did not observe significant association of the most studied SNP, rs371194629 (INDEL, +2960), with HCC or treatment response. Serum sHLA-G levels were found to be significantly (p = 0.027) higher in HCC patients as compared to healthy controls. Highly prevalent UTR haplotypes in Indian HCC patients were UTR-4, -1, and -7 whereas in healthy controls it was UTR-3, and 15 as determined by a linkage disequilibrium (LD) plot using 8 SNPs.Haplotypes associated with high levels of HLA-G expression are more prevalent in HCC than in healthy controls.Core Tip: Population genetic approaches were used to study HLA-G gene polymorphisms in the Indian population for its genetic association with HCC risk, treatment response and altered gene expression. Out of the 14 SNPs studied for HLA-G UTR, three were linked to HCC and response to locoregional therapy. Linkage disequilibrium and UTR haplotyping analysis show that the UTR-4 haplotype linked to high HLA-G levels, is more common in HCC patients, while the UTR-3 haplotype, linked to low HLA-G levels, is more common in healthy controls. This study is the first to look at the UTR types based on HLA-G gene polymorphisms of Indian HCC patients and their response to therapy.

    Keywords: HLA-G, HCC, Genetic association, SNPs (Single nucleotide polymorphism), Therapeutic response, UTR

    Received: 04 Jul 2024; Accepted: 17 Oct 2024.

    Copyright: © 2024 Nadda, Yadav, Roy, Singh, KUMAR, Paul, Gammanagatti, Saraya, Shalimar and Nayak. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Baibaswata Nayak, All India Institute of Medical Sciences, New Delhi, India

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