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Tenascin-C as a potential biomarker and therapeutic target for esophageal squamous cell carcinoma.

Tenascin-C as a potential biomarker and therapeutic target for esophageal squamous cell carcinoma.

Authors :
Liu Y
Yang LY
Chen DX
Chang C
Yuan Q
Zhang Y
Cai Y
Wei WQ
Hao JJ
Wang MR
Source :
Translational oncology [Transl Oncol] 2024 Apr; Vol. 42, pp. 101888. Date of Electronic Publication: 2024 Feb 14.
Publication Year :
2024

Abstract

Purpose: To establish a prognostic model of esophageal squamous cell carcinoma (ESCC) patients based on tenascin-C (TNC) expression level and clinicopathological characteristics, and to explore the therapeutic potential of TNC inhibition.<br />Methods: The expression of TNC was detected using immunohistochemistry (IHC) in 326 ESCC specimens and 50 normal esophageal tissues. Prognostic factors were determined by Cox regression analyses and were incorporated to establish the nomogram. The effects of TNC knockdown on ESCC cells were assessed in vitro and in vivo. Transcriptome sequencing (RNA-seq) and gene set enrichment analysis (GSEA) were performed to reveal signaling pathways regulated by TNC knockdown. The therapeutic significance of TNC knockdown combined with small-molecule inhibitors on cell proliferation was examined.<br />Results: TNC protein was highly expressed in 48.77 % of ESCC tissues compared to only 2 % in normal esophageal epithelia (p < 0.001). The established nomogram model, based on TNC expression, pT stage, and lymph node metastasis, showed good performance on prognosis evaluation. More importantly, the reduction of TNC expression inhibited tumor cell proliferation and xenograft growth, and mainly down-regulated signaling pathways involved in tumor growth, hypoxia signaling transduction, metabolism, infection, etc. Knockdown of TNC enhanced the inhibitory effect of inhibitors targeting ErbB, PI3K-Akt, Ras and MAPK signaling pathways.<br />Conclusion: The established nomogram may be a promising model for survival prediction in ESCC. Reducing TNC expression enhanced the sensitivity of ESCC cells to inhibitors of Epidermal Growth Factor Receptor (EGFR) and downstream signaling pathways, providing a novel combination therapy strategy.<br />Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.<br /> (Copyright © 2024. Published by Elsevier Inc.)

Details

Language :
English
ISSN :
1936-5233
Volume :
42
Database :
MEDLINE
Journal :
Translational oncology
Publication Type :
Academic Journal
Accession number :
38354632
Full Text :
https://doi.org/10.1016/j.tranon.2024.101888