An Integrated Analysis Identified TAGLN2 As an Oncogene Indicator Related to Prognosis and Immunity in Pan-Cancer

Abstract

Background: Transgelin-2 (TAGLN2) has long been regarded as an actin-binding protein that modulates actin gelation and controls actin cytoskeleton dynamics. However, recent studies have reported that TAGLN2 can directly or indirectly participate in multiple cancer-related processes, including cell migration, proliferation, differentiation, and apoptosis. To further investigate the role of TAGLN2 in carcinogenesis, a comprehensive analysis was launched to evaluate the expression status and prognostic value of TAGLN2 in pan-cancer. Methods: Herein, data was retrieved from publicly online websites and databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), UCSC Xena, cBioPortal, Human Protein Atlas (HPA), TIMER2.0, CancerSEA, GDSC, and ImmuCellAI. Gene expression pattern and its correlation with prognosis were assessed across cancer types. Moreover, an analysis was conducted to explore the relationships between TAGLN2 and methylation, copy number values (CNVs), tumor microenvironment (TME), immune cell infiltration, immune-relevance genes, tumor mutation burden (TMB), microsatellite instability (MSI), and IC50. Additionally, R package “clusterProfiler” was utilized to perform enrichment analysis on TAGLN2. Finally, the ability of TAGLN2 as an oncogene was preliminarily verified in vitro in UCEC. Results: Our findings revealed that TAGLN2 was specifically overexpressed and related to an unfavorable prognosis in most cancers. There was a significant connection between TAGLN2 expression and methylation and CNVs. Besides, we identified TAGLN2 correlated to TME, immune cell infiltration, immune-relevant genes, TMB, and MSI, suggesting an immunoregulatory role in cancers. Notably, TAGLN2 expression showed a positive correlation with macrophages, and cancer-associated fibroblasts, whereas a negative correlation with the infiltration degree of B cells. Mechanically, the results obtained from Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) provided theory-supportive evidence that TAGLN2 interlinkages with immunity and programmed cell death. Overall, anti-tumor drugs were overtly associated with TAGLN2 dysregulation among diverse cancers. At last, UCEC cell lines with TAGLN2-depleting had an inhibition of the migration and invasion ability. Conclusions: These findings enriched the knowledge about the role of TAGLN2 in tumorigenesis and progression, revealing TAGLN2 may serve as a potential therapeutic strategy for various malignancies.

Proteomic profiling of formalin-fixed paraffine-embedded tissue reveals key proteins related to lung dysfunction in idiopathic pulmonary fibrosis

“…TAGLN2 was identified as a biomarker in the development of pulmonary fibrosis since it triggered the activation of the TGF-beta/Smad3-pathway ( 72 ). Moreover, several studies stated that TAGLN2 can modulate multiple cancer-related processes, including cell migration, proliferation, differentiation, and apoptosis in glioma and gastric cancer ( 73 ), ( 74 ). Finally, PRDX2 which encodes a member of the peroxiredoxin family of antioxidant enzymes, was found up-regulated among 30 proteins in fibrotic kidney fibroblasts (TK188) compared to normal kidney fibroblast (TK173), suggesting a role in the progression of renal fibrosis ( 75 ).…”

Identification and validation of a platelet-related signature for predicting survival and drug sensitivity in multiple myeloma

“…Moreover, TAGLN2 governs the dynamics of the cytoskeletal protein actin by reinforcing actin filaments and plays a crucial role in the remodeling procedures of the actin cytoskeleton, encompassing cellular proliferation, differentiation, migration, and programmed cell death ( Dutta et al, 2021 ). Various studies have shown that potentially carcinogenic factor TAGLN2 is altered at the transcriptional and translational levels in a variety of malignancies, including as leukemia, breast cancer, colorectal cancer and lymphoma ( Zhao et al, 2021 ; Pan et al, 2023 ). It has also been suggested that TAGLN2 is associated with angiogenesis ( Zhao et al, 2021 ).…”

Transgelin-2, a novel cancer stem cell-related biomarker, is a diagnostic and therapeutic target for biliary tract cancer

“…A recent study exploring the role of TAGLN2 in cancer demonstrated its association with multidrug resistance and metastasis in breast cancer, emphasizing the potential of TAGLN2 -targeted therapies [ 35 ]. Furthermore, TAGLN2 has been identified as an oncogene related to prognosis and immunity across various cancers [ 31 ], and its involvement in tumor proliferation and migration in colorectal cancer has also been documented [ 28 ].…”