# Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer

## TL;DR

This study explores the role of the integrator complex in gastric cancer, finding that it may act as an oncogene and could help predict patient outcomes.

## Contribution

The study provides the first comprehensive analysis of integrator complex subunits in gastric cancer, linking them to prognosis and tumor microenvironment features.

## Key findings

- INT subunit expressions were significantly elevated in gastric cancer datasets.
- INT subunits are associated with tumor-infiltrating lymphocytes and microsatellite instability in gastric cancer.
- Knockdown of INTS11 inhibits gastric cancer cell proliferation, while its overexpression promotes it.

## Abstract

The integrator complex (INT) is a multiprotein assembly in gene transcription. Although several subunits of INT complex have been implicated in multiple cancers, the complex’s role in gastric cancer (GC) is poorly understood.

The gene expressions, prognostic values, and the associations with microsatellite instability (MSI) of INT subunits were confirmed by GEO and The Cancer Genome Atlas (TCGA) databases. cBioPortal, GeneMANIA, TISIDB, and MCPcounter algorithm were adopted to investigate the mutation frequency, protein–protein interaction network, and the association with immune cells of INT subunits in GC. Additionally, in vitro experiments were performed to confirm the role of INTS11 in pathogenesis of GC.

The mRNA expression levels of INTS2/4/5/7/8/9/10/11/12/13/14 were significantly elevated both in GSE183904 and TCGA datasets. Through functional enrichment analysis, the functions of INT subunits were mainly associated with snRNA processing, INT, and DNA-directed 5′–3′ RNA polymerase activity. Moreover, these INT subunit expressions were associated with tumor-infiltrating lymphocytes and MSI in GC. In vitro experiments demonstrated that knockdown of the catalytic core INTS11 in GC cells inhibits cell proliferation ability. INTS11 overexpression showed opposite effects.

Our data demonstrate that the INT complex might act as an oncogene and can be used as a prognosis biomarker for GC.