Comprehensive analysis of prognostic value and immune infiltration of kindlin family members in non-small cell lung cancer

Abstract

Background Kindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated. Methods We analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan‑Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR. Results The expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC. Conclusions The research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.

FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling

“…So far, studies have shown that FERMT3 plays crucial roles in important physiological and pathological processes, including integrin activation-mediated signaling, cell adhesion and migration, immune regulation, and cancer progression [ 12 – 14 ]. It was found that FERMT3 expression was down-regulated in lung cancer, and depletion of FERMT3 enhances cell proliferation, migration, and invasion in lung cancer cells [ 13 , 15 ]. Nevertheless, the role of FERMT3 in EMT and COPD has not been reported.…”

Blockage of PD‐L1 by FERMT3‐mediated Wnt/β‐catenin signalling regulates chemoresistance and immune evasion of colorectal cancer cells

“…However, another study substantiates the downregulation of FERMT3 in melanoma, breast cancer and kidney cancer; moreover, FERMT3 can act as a suppressor to affect cancer cell proliferation, invasion and migration 14 . Intriguingly, different from the increased expression of FERMT1 in non–small cell lung cancer tissues, FERMT3 decreases in tumour tissues and is correlated with diverse immune cell infiltration 15 . Additionally, kindlin‐3 lowers the threshold for NK cell activation, implying the potential role in tumour immune 16 .…”

“…14 Intriguingly, different from the increased expression of FERMT1 in non-small cell lung cancer tissues, FERMT3 decreases in tumour tissues and is correlated with diverse immune cell infiltration. 15 Additionally, kindlin-3 lowers the threshold for NK cell activation, implying the potential role in F I G U R E 1 FERMT3 is expressed at low levels in CRC tissues and cells. A,B, The expression levels of FERMT3 in CRC tissues were analysed using the online bioinformatics database UALCAN, A, and GEPIA, B. C,D, qRT-PCR, C, and western blotting D, were used to determine the mRNA and protein levels of FERMT3 in CRC tissues and adjacent normal tissues.…”

Transcriptomic meta-analysis of non-Hodgkin’s B-cell lymphomas reveals reliance on pathways associated with the extracellular matrix

“…The role of YES1 in BCNHL pathogenesis also needs additional investigation. FERMT2 has previously been pinpointed as a biomarker for other cancers previously including non-small cell lung cancer and prostate cancer (65,66), but not for BCNHL. FERMT2 stabilizes CTNNB1, which is a well-documented activator of oncogene transcription, and is implicated in Wnt pathway regulation (67).…”