Comprehensive investigation of cytokine- and immune-related gene variants in HBV-associated hepatocellular carcinoma patients

Abstract

Host genotype may be closely related to the different outcomes of Hepatitis B virus (HBV) infection. To identify the association of variants and HBV infection, we comprehensively investigated the cytokine- and immune-related gene mutations in patients with HBV associated hepatocellular carcinoma (HBV-HCC). Fifty-three HBV-HCC patients, 53 self-healing cases (SH) with HBV infection history and 53 healthy controls (HCs) were recruited, the whole exon region of 404 genes were sequenced at >900× depth. Comprehensive variants and gene levels were compared between HCC and HC, and HCC and SH. Thirty-nine variants (adjusted P<0.0001, Fisher’s exact test) and 11 genes (adjusted P<0.0001, optimal unified approach for rare variant association test (SKAT-O) gene level test) were strongly associated with HBV-HCC. Thirty-four variants were from eight human leukocyte antigen (HLA) genes that were previously reported to be associated with HBV-HCC. The novelties of our study are: five variants (rs579876, rs579877, rs368692979, NM_145007:c.*131_*130delTG, NM_139165:exon5:c.623-2->TT) from three genes (REAT1E, NOD-like receptor (NLR) protein 11 (NLRP11), hydroxy-carboxylic acid receptor 2 (HCAR2)) were found strongly associated with HBV-HCC. We found 39 different variants in 11 genes that were significantly related to HBV-HCC. Five of them were new findings. Our data implied that chronic hepatitis B patients who carry these variants are at a high risk of developing HCC.

Diagnostic and prognostic biomarkers of Human Leukocyte Antigen complex for hepatitis B virus-related hepatocellular carcinoma

“…Dianwu Liu et al suggested that thirty four variants of eight HLA genes, including HLA-B, HLA-C, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DQB2, HLA-DRB1 , and HLA-DRB5 , were strongly associated with HBV-related HCC 50. Weiping Zhou et al suggested that new associations at rs9272105 ( HLA-DQA1/DRB1 ) on 6p21.32 (odds ratio=1.30, P =1.13E-19) 51.…”

Innate and Adaptive Immune Genes Associated with MERS-CoV Infection in Dromedaries

“…We decided to use a target enrichment approach with in-solution hybridization capture of 100 annotated immune genes [ 24 ] to genotype a larger number of dromedaries tested for a recent infection of MERS-CoV. Targeted enrichment has successfully been applied in sequencing the IR genes of gopher tortoises [ 32 ], in assessing variants in immune genes associated with Hepatitis B virus infection [ 33 ] and in identifying somatic alterations in follicular dendritic cell sarcoma in known cancer-associated genes [ 34 ].…”

Cytokines, breast cancer stem cells (BCSCs) and chemoresistance

“…In the course of chemotherapy for breast cancer patients, common chemotherapeutic drugs target non-cancer stem cells, but the cancer stem cells can survive and further cause recurrence or even metastasis due to their own characteristics. Therefore, breast cancer stem cells are considered to be the key population leading to drug resistance of breast cancer [ 14 , 15 ]. With the development of molecular markers of breast cancer stem cells, researchers have found that a small population of cells, selected by markers, can lead to the initiation of tumors, which further confirms the vital role of cancer stem cells in tumor initiation [ 16 , 17 ].…”