A pan-cancer analysis of GINS complex subunit 4 to identify its potential role as a biomarker in multiple human cancers

Muhammad Usman; Mohammad K Okla; Hafiz Muhammad Asif; Gehad AbdElgayed; Fatima Muccee; Shakira Ghazanfar; Mukhtiar Ahmad; Muhammad Junaid Iqbal; Aamina Murad Sahar; Ghania Khaliq; Rabbia Shoaib; Hira Zaheer; Yasir Hameed

A pan-cancer analysis of GINS complex subunit 4 to identify its potential role as a biomarker in multiple human cancers

Am J Cancer Res. 2022 Mar 15;12(3):986-1008. eCollection 2022.

Authors

Affiliations

¹ Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur Bahawalpur 63100, Pakistan, Pakistan.
² Department of Botany and Microbiology, College of Science, King Saud University Riyadh 11451, Saudi Arabia.
³ University College of Conventional Medicine, Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur Bahawalpur 63100, Pakistan.
⁴ Integrated Molecular Plant Physiology Research, Department of Biology, University of Antwerp 2020 Antwerp, Belgium.
⁵ Department of Biotechnology, Virtual University of Pakistan Lahore 54000, Pakistan.
⁶ Functional Genomics and Bioinformatics, National Agricultural Research Centre Islamabad 45500, Pakistan.
⁷ Department of Biosciences, COMSATS University Islamabad 44000, Pakistan.
⁸ Department of Biosciences, COMSATS University Islamabad Islamabad 4400, Pakistan.
⁹ Department of Zoology, Cholistan University of Veterinary and Animal Sciences Bahawalpur Bahawalpur 63100, Pakistan.
¹⁰ Department of Chemistry, Government College University Faisalabad Faisalabad 3800, Pakistan.

PMID: 35411239
PMCID: PMC8984884

Abstract

This study was initiated to explore the expression variation, clinical significance, and biological importance of the GINS complex subunit 4 (GINS4) in different human cancers as a shared biomarker via pan-cancer analysis through different platforms including UALCAN, Kaplan Meier (KM) plotter, TNMplot, GENT2, GEPIA, DriverDBv3, Human Protein Atlas (HPA), MEXPRESS, cBioportal, STRING, DAVID, MuTarge, Enrichr, TIMER, and CTD. Our findings have verified the up-regulation of GINS4 in 24 major subtypes of human cancers, and its overexpression was found to be substantially associated with poor overall survival (OS), relapse-free survival (RFs), and metastasis in ESCA, KIRC, LIHC, LUAD, and UCEC. This suggested that GINS4 plays a significant role in the development and progression of these five cancers. Furthermore, we noticed that GINS4 is also overexpressed in ESCA, KIRC, LIHC, LUAD, and UCEC patients with different clinicopathological characteristics. Enrichment analysis revealed the involvement of GINS4 associated genes in a variety of diverse GO and KEGG terms. We also explored few significant correlations between GINS4 expression and promoter methylation, genetic alterations, CNVs, other mutant genes, tumor purity, and immune cells infiltration. In conclusion, our results elucidated that GINS4 can serve as a shared diagnostic, prognostic biomarker, and a potential therapeutic target in ESCA, KIRC, LIHC, LUAD, and UCEC patients with different clinicopathological characteristics.

Keywords: GINS4; biomarker; cancer; expression variations; tumor purity.