Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways

Abstract

Background: Inhibitors targeting integrins (ITGs) are applied as a novel strategy for cancers including lung cancer; however, the heterogeneity of ITG subunits might explain why ITG-targeted inhibitors only show limited efficacy for a small group of lung cancer patients. Materials and methods: RNA-Seq data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients were obtained from the TCGA database. Cox regression analysis was performed to construct the prognostic signature and generate the nomogram combined with pathologic stages (pStage). GEO datasets were used for verification. The related biological functions were analyzed by Gene Set Enrichment Analysis (GSEA) software and the TIMER database. Results: By Cox regression analysis of 30 ITG subunits, ITG subunit alpha 5 (ITGA5), ITG subunit alpha 6 (ITGA6), and ITG subunit alpha L (ITGAL) were identified as the prognostic factors in LUAD, which were included in the construction of a LUAD-specific 3-ITG signature. Following the calculation of risk score (RS) of each patient based on 3-ITG signature, patients with high RS in LUAD were found to exhibit worse prognosis, especially in early stage. Nomogram combined with RS and pStage could predict the prognosis of LUAD patients accurately. Mechanism exploration by GSEA showed that metastasis-related microenvironmental pathways were significantly enriched in the high-RS group. An elevated expression of ITGA5 was mainly associated with the promotion of cell migration and invasion, while the high expression of ITGAL had a strong positive correlation with the capability of recognizing and killing cancer cells. Conclusions: Three-ITG signature could improve the prediction ability combined with pStage in LUAD and might contribute to poor prognosis by metastasis and immune escape-related pathways.

A detection panel of novel methylated DNA markers for malignant pleural effusion

“…A number of studies have demonstrated frequent promoter methylation in lung cancer cells, including short stature homeobox gene two (SHOX2), RAS association domain family 1, isoform A (RASSF1A) (6)(7)(8) and homeobox A9 (HOXA9) (9,10). HOXA9 promoter hypermethylation has also been observed in a large proportion of high-grade serous ovarian carcinomas (11).…”

Screening of ferroptosis-related genes with prognostic effect in colorectal cancer by bioinformatic analysis

“…Besides, He et al demonstrated that aberrantly expressed MT1G also affected the immune response of CRC patients ( Peng et al, 2022 ). Immune escape is an important reason for tumor treatment failure and the change of tumor environment caused by ferroptosis may be responsible for it ( Xu et al, 2020 ; Wang et al, 2021 ). According to our results, the ATG7, MAPK9 and MMD were independent ferroptosis-related genes that can used as prognosis markers.…”

Polysaccharide immunization and colorectal cancer: A systematic review and network meta-analysis

“…It may have a particular reference value in future tumor differential diagnosis and targeted therapy. Examples include exosomal MiR-155 and MiR-665 as new hepatocellular carcinoma biomarkers (49), and ITGs as indicators of immune escape in NSCLC (50). Tumorrelated markers can be analyzed from multiple perspectives and in multiple dimensions to consider the development of tumors and their prognosis.…”