<i>FN1</i> and cancer‐associated fibroblasts markers influence immune microenvironment in clear cell renal cell carcinoma

Ashok, Gayathri; Ramaiah, Sudha

doi:10.1002/jgm.3556

Cited by 10 publications

(1 citation statement)

References 59 publications

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“…The timely and accurate detection of LUAD requires the specific identification of tumor cell biomarkers, hence in our present study, we applied an integrated in silico approach 13–21 to comprehensively understand the functional significance of MUC5B in LUAD by gene expression profiling, clustering‐functional enrichment analyses, genetic alterations, tumor‐immune cell infiltration and glycosylation patterns. Further, the potentiality of MUC5B as theranostic biomarker was validated using clinical profile and survival analyses.…”

Section: Introductionmentioning

confidence: 99%

Elucidating the molecular role of MUC5B in progressive lung adenocarcinoma: Prospects for early diagnosis

Ashok,

Soundararajan,

Anbarasu

et al. 2023

J of Molecular Recognition

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Gel‐forming mucin MUC5B is significantly deregulated in lung adenocarcinoma (LUAD), however, its role in tumor progression is not yet clearly understood. Here, we used an integrated computational‐pipeline‐initiated with gene expression analysis followed by network, functional‐enrichment, O‐linked glycosylation analyses, mutational profiling, and immune cell infiltration estimation to functionally characterize MUC5B gene in LUAD. Thereafter, clinical biomarker validation was supported by the overall survival (OA) and comparative expression profiling across clinical stages using computational algorithms. The gene expression profile of LUAD identified MUC5B to be significantly up‐regulated (logFC: 2.36; p‐value: 0.01). Network analysis on LUAD interactome screened MUC5B‐related genes, having key enrichment in immune suppression and O‐linked glycosylation with serine–threonine‐rich tandem repeats being highly glycosylated. Furthermore, positive correlation of mutant MUC5B with immune cells in tumor microenvironment (TME) such as cancer‐associated fibroblasts and myeloid‐derived suppressor cells indicates TME‐mediated tumor progression. The positive correlation with immune inhibitors suggested the enhanced tumor proliferation mediated by MUC5B. Structural stability due to genetic alterations identified overall rigid N–H‐backbone dynamics (S2: 0.756), indicating an overall stable mutant protein. Moreover, the low median OA (<50 months) with a hazard ratio of 1.4 and clinical profile of MUC5B gene showed high median expression corresponding to lymph node (N2) and tumor (T3) stages. Our study concludes by highlighting the functional role of O‐glycosylated and mutant MUC5B in promoting LUAD by immune suppression. Further, clinical gene expression validation of MUC5B suggests its potential role as a diagnostic biomarker for LUAD metastasis.

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Section: Introductionmentioning

confidence: 99%