Integrated Bioinformatic Analysis Identifies TIPIN as a Prognostic Biomarker in Hepatocellular Carcinoma

Abstract

Background. Gene expression and DNA methylation analyses have long been used to identify cancer markers. However, a combination analysis of the gene expression and DNA methylation has yet to be performed to identify potential biomarkers of hepatocellular carcinoma (HCC). Methods. By matching gene expression profiles and promoter methylation data in The Cancer Genome Atlas (TCGA), genes with discrepant expression as well as genes with differential promoter methylation were identified. High-expression genes with low promoter methylation were defined as epigenetically induced (EI), while low-expression genes with high promoter methylation were defined as epigenetically suppressed (ES). The human protein interaction network was further integrated to construct the EI/ES gene interaction network, and the key genes in the subnet were identified as potential HCC biomarkers. The expression differences and prognostic values were verified in TCGA and Gene Expression Omnibus (GEO) databases, as well as with tissue chip technology. Results. Four key genes were identified: TIPIN, RBM15B, DUSP28, and TRIM31, which demonstrated the differential gene expression and prognostic value in TCGA and GEO databases. Tissue microarray analysis (TMA) revealed that TIPIN levels were altered in HCC. The upregulated TIPIN expression was associated with worse overall survival. Univariate and multivariate analyses showed that the TIPIN expression was an independent predictor of HCC. Conclusion. TIPIN might be a potential novel prognostic biomarker for HCC.

Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors

“…DNA repair genes over-expressed in constant ph -KD tumors include several components previously linked to damage accumulation, cancer formation, and/or poor cancer prognosis ( Table 1 ), like Mms4 ( Dewalt, Kesler et al 2014 ), RecQ4 ( Maire, Yoshimoto et al 2009 , Su, Meador et al 2010 , Xu, Chang et al 2021 ), PolH ( Tomicic, Aasland et al 2014 , Sonobe, Yang et al 2024 ), Tipin/Timeless ( Zhou, Zhang et al 2020 , Chen, Zhang et al 2022 ), Claspin ( Choi, Yang et al 2014 ), MRNIP ( Staples, Barone et al 2016 , Bennett, Wilkie et al 2020 , Wang, Zhao et al 2022 ), FANCI ( Smogorzewska, Matsuoka et al 2007 , Li, Yu et al 2023 ), MMR proteins (Msh2, Mlh1, Msh6) ( Shcherbakova and Kunkel 1999 , Velasco, Albert et al 2002 , Li, Liu et al 2008 , Wagner, Webber et al 2016 , Wilczak, Rashed et al 2017 , Chakraborty, Dinh and Alani 2018 , Donis, Gonzalez et al 2021 , Zhou, Xiao and Chen 2024 ), and Rif1 ( Liu, Mei et al 2018 , Mei, Liu et al 2018 , Sad, Mohamed et al 2021 ). Similarly, genes down regulated in constant ph -KD tumors include known components required for DNA repair and replication fork protection in the presence of replication damage, like the PCNA variant PCNA2 ( Feng, Xia et al 2023 ) ( Table 1 ).…”

Prognostic relationship between TIPIN and colorectal cancer and experimental validation

“…Similarly in triple-negative breast cancer samples mRNA levels of TIPIN were significantly higher than specimens from other breast cancer subgroups and healthy tissues, protein levels of TIPIN were able to make breast cancer subtypes more invasive and proliferative, and TIPIN depletion reduced the tumorigenicity of triple-negative breast cancer cells [9]. In addition TIPIN is overexpressed in hepatocellular carcinoma at both mRNA and protein levels, and high expression of TIPIN is also associated with poor prognosis in patients with hepatocellular carcinoma [16]. In addition TIPIN expression was downregulated in renal tumors compared to normal tissues and may be associated with dysregulation of cell cycle checkpoints [17] .…”

Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma

“…ICD plays an important role in the development of cancers. Several studies have been conducted to explore some of the genes that influence the prognosis of HCC ( Rao et al, 2021 ; Chen et al, 2022 ). However, the role of ICD associated genes in the prognosis of HCC had not been explored.…”