Comprehensive bioinformatics analysis of integrator complex subunits: expression patterns, immune infiltration, and prognostic signature - validated through experimental approaches in hepatocellular carcinoma

Sep 21, 2026

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Hepatocellular carcinoma (HCC) is a prevalent gastrointestinal malignancy with high incidence and poor prognosis. Integrator complex subunits (INTS1–14) regulate RNA Polymerase II–dependent genes and may influence cancer, yet their roles in HCC remain insufficiently defined. This study performs systematic bioinformatics analysis to assess the clinical value and potential mechanisms of INTS family genes, integrating expression, clinicopathological associations, diagnosis/prognosis, genetic alterations, molecular targets, and immune infiltration.

LanguageEnglish

CategoryResearch & Report

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Pages19

Reading Time48 min

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Abstract

Background

Methods

Results

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Introduction

Research Comprehensive bioinformatics analysis of integrator complex subunits: expression patterns, immune infiltration, and prognostic signature, validated through experimental approaches in hepatocellular carcinoma Yifei Xu1 · Wenlian Liao1 · Ting Wang1 · Liwei Zhang2 · Hui Zhang1 Received: 12 January 2024 / Accepted: 21 June 2024 © The Author(s) 2024 OPEN Abstract Background Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy with a high incidence and poor prognosis. The subunits of the integrator complex (INTS1-14) play a crucial role in regulating genes dependent on RNA Polymerase II, which may be associated with cancer. However, the role of INTSs in HCC remains unclear. This study aims to comprehensively analyze the clinical value and potential role of INTS family genes in HCC through systematic bioinformatics analysis. Methods We employed various public databases, including UALCAN, HPA, Kaplan–Meier Plotter, GEPIA2, TNMplot, STRING, TIMER, and TISIDB, to investigate the expression levels, clinicopathological correlations, diagnostic and prognostic value, genetic alterations, co-expression network, molecular targets, and immune infiltration of INTSs in HCC. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to investigate the biological functions of genes associated with INTSs. Furthermore, Western blot, real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and immunohistochemistry techniques were employed to assess the expression of relevant proteins and genes. The proliferation of HCC cells was evaluated using the CCK8 assay. Results We found that in HCC, there was a significant upregulation of INTSs at the transcriptional level, particularly INTS1, INTS4, INTS7, and INTS8. Additionally, the protein levels of INTS1 and INTS8 were notably elevated. The overexpression of these INTSs was strongly correlated with tumor stages in HCC patients. INTS1, INTS4, INTS7, and INTS8 exhibited significant diagnostic and prognostic value in HCC. Moreover, their expression was associated with immune infiltrationsand activated status, including B cells, CD8 + T cells, CD4 + T cells, NK cells, macrophages, and dendritic cells. Functional predictions indicated that INTS1, INTS4, INTS7, and INTS8 were involved in various cancer-related signaling pathways, such as TRAIL, IFN-gamma, mTOR, CDC42, Apoptosis, and the p53 pathway. Furthermore, we observed a significant upregulation of INTS1, INTS4, INTS7, and INTS8 expression in HCC cell lines compared to normal liver cell lines. The level Yifei Xu and Wenlian Liao have contributed equally to this work. Supplementary Information The online version contains supplementary material available at [https://doi.org/10.1007/s12672-024-](https://doi.org/10.1007/s12672-024-)[ ](https://doi.org/10.1007/s12672-024-)[01118-6](01118-6.)[.](01118-6.) * Liwei Zhang, [14159078@qq.com](14159078@qq.com); * Hui Zhang, [zhanghuiman@126.com](zhanghuiman@126.com); Yifei Xu, [2364161978@qq.com](2364161978@qq.com); Wenlian Liao, [lwl17317327182@163.com](lwl17317327182@163.com); Ting Wang, [wangting9485@163.com |](wangting9485@163.com |1Institute of)[1](wangting9485@163.com |1Institute of)[Institute of](wangting9485@163.com |1Institute of) Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. 2Department of Anesthesiology, School of Medicine, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen 361101, Fujian, China. Discover Oncology (2024) 15:246 | [https://doi.org/10.1007/s12672-024-01](https://doi.org/10.1007/s12672-024-01)118-6 of INTS1 protein was higher in cancerous tissues compared to adjacent non-cancerous tissues (n = 16), and the suppression of INTS1 resulted in a significant decrease in the proliferation of Huh7 cells. Conclusion These findings indicate the potential of INTS family genes as

FAQs

What is the main goal of the study on integrator complex subunits in HCC?

To comprehensively evaluate the clinical value and potential role of INTS family genes in hepatocellular carcinoma using systematic bioinformatics analysis and experimental validation.

Which INTS subunits showed notable upregulation in HCC?

INTS1, INTS4, INTS7, and INTS8 were significantly upregulated at the transcriptional level, with protein levels of INTS1 and INTS8 also notably elevated.

How are INTS1, INTS4, INTS7, and INTS8 related to prognosis and immune infiltration?

Their expression is associated with tumor stages and shows diagnostic and prognostic value in HCC. It is also linked to immune infiltration and activated immune status across multiple cell types, indicating relevance to the tumor immune microenvironment.

Sep 21, 2026

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