Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence

Dysregulated immune response significantly affects hepatocellular carcinoma’s (HCC) prognosis. Human Leukocyte Antigens are key in devising immune responses against HCC. Here, we investigated how HLAs modulate HCC development at the transcriptomic level. RNA-seq data of 576 patients from two indepen...

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Autores principales:	Fomaz Tariq, Walizeb Khan, Washaakh Ahmad, Syeda Kiran Riaz, Mahvish Khan, Subuhi Sherwani, Shafiul Haque, Muhammad Faraz Arshad Malik, Muhammad Jahangir Iftikhar, Saif Khan, Farhan Haq
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	MHC HCC gene signature HLAs immune-modulators Medicine R
Acceso en línea:	https://doaj.org/article/743d35859f7e4355b9636a3e4b6881a8
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spelling	oai:doaj.org-article:743d35859f7e4355b9636a3e4b6881a82021-11-25T18:07:25ZEffect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence10.3390/jpm111111292075-4426https://doaj.org/article/743d35859f7e4355b9636a3e4b6881a82021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1129https://doaj.org/toc/2075-4426Dysregulated immune response significantly affects hepatocellular carcinoma’s (HCC) prognosis. Human Leukocyte Antigens are key in devising immune responses against HCC. Here, we investigated how HLAs modulate HCC development at the transcriptomic level. RNA-seq data of 576 patients from two independent cohorts was retrieved. The clinicopathological relevance of all HLA genes was investigated using Fisher-Exact, correlation, and Kaplan–Meier and cox regression survival tests. Clustering of ~800 immune-related genes against HLAs was completed using a ward-agglomerative method. Networks were generated using 40 HLA associated unique genes and hub genes were investigated. HLAs including HLA-DMA, HLA-DMB, HLA-DOA and HLA-DRB6 were associated with delayed recurrence in both discovery (204 HCC cases) and validation (372 HCC cases) cohorts. Clustering analyses revealed 40 genes associated with these four HLAs in both cohorts. A set of seven genes (NCF4, TYROBP, LCP2, ZAP70, PTPRC, FYN and WAS) was found co-expressed at gene–gene interaction level in both cohorts. Furthermore, survival analysis revealed seven HLA-linked genes as predictors of delayed recurrence. Multivariate analysis also predicted that mean expression of 7-gene is an independent predictor of delayed recurrence in both cohorts. We conclude that the expression of 7-gene signature may lead to improved patient prognosis. Further studies are required for consideration in clinical practice.Fomaz TariqWalizeb KhanWashaakh AhmadSyeda Kiran RiazMahvish KhanSubuhi SherwaniShafiul HaqueMuhammad Faraz Arshad MalikMuhammad Jahangir IftikharSaif KhanFarhan HaqMDPI AGarticleMHCHCCgene signatureHLAsimmune-modulatorsMedicineRENJournal of Personalized Medicine, Vol 11, Iss 1129, p 1129 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MHC HCC gene signature HLAs immune-modulators Medicine R
spellingShingle	MHC HCC gene signature HLAs immune-modulators Medicine R Fomaz Tariq Walizeb Khan Washaakh Ahmad Syeda Kiran Riaz Mahvish Khan Subuhi Sherwani Shafiul Haque Muhammad Faraz Arshad Malik Muhammad Jahangir Iftikhar Saif Khan Farhan Haq Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence
description	Dysregulated immune response significantly affects hepatocellular carcinoma’s (HCC) prognosis. Human Leukocyte Antigens are key in devising immune responses against HCC. Here, we investigated how HLAs modulate HCC development at the transcriptomic level. RNA-seq data of 576 patients from two independent cohorts was retrieved. The clinicopathological relevance of all HLA genes was investigated using Fisher-Exact, correlation, and Kaplan–Meier and cox regression survival tests. Clustering of ~800 immune-related genes against HLAs was completed using a ward-agglomerative method. Networks were generated using 40 HLA associated unique genes and hub genes were investigated. HLAs including HLA-DMA, HLA-DMB, HLA-DOA and HLA-DRB6 were associated with delayed recurrence in both discovery (204 HCC cases) and validation (372 HCC cases) cohorts. Clustering analyses revealed 40 genes associated with these four HLAs in both cohorts. A set of seven genes (NCF4, TYROBP, LCP2, ZAP70, PTPRC, FYN and WAS) was found co-expressed at gene–gene interaction level in both cohorts. Furthermore, survival analysis revealed seven HLA-linked genes as predictors of delayed recurrence. Multivariate analysis also predicted that mean expression of 7-gene is an independent predictor of delayed recurrence in both cohorts. We conclude that the expression of 7-gene signature may lead to improved patient prognosis. Further studies are required for consideration in clinical practice.
format	article
author	Fomaz Tariq Walizeb Khan Washaakh Ahmad Syeda Kiran Riaz Mahvish Khan Subuhi Sherwani Shafiul Haque Muhammad Faraz Arshad Malik Muhammad Jahangir Iftikhar Saif Khan Farhan Haq
author_facet	Fomaz Tariq Walizeb Khan Washaakh Ahmad Syeda Kiran Riaz Mahvish Khan Subuhi Sherwani Shafiul Haque Muhammad Faraz Arshad Malik Muhammad Jahangir Iftikhar Saif Khan Farhan Haq
author_sort	Fomaz Tariq
title	Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence
title_short	Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence
title_full	Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence
title_fullStr	Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence
title_full_unstemmed	Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence
title_sort	effect of mhc linked 7-gene signature on delayed hepatocellular carcinoma recurrence
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/743d35859f7e4355b9636a3e4b6881a8
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Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence

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