PMID- 38354632 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240223 IS - 1936-5233 (Print) IS - 1936-5233 (Electronic) IS - 1936-5233 (Linking) VI - 42 DP - 2024 Apr TI - Tenascin-C as a potential biomarker and therapeutic target for esophageal squamous cell carcinoma. PG - 101888 LID - S1936-5233(24)00014-7 [pii] LID - 10.1016/j.tranon.2024.101888 [doi] LID - 101888 AB - 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. 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. 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. 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. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Liu, Yang AU - Liu Y AD - State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Yang, Li-Yan AU - Yang LY AD - State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Chen, Ding-Xiong AU - Chen DX AD - State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Chang, Chen AU - Chang C AD - State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Yuan, Qing AU - Yuan Q AD - State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Zhang, Yu AU - Zhang Y AD - State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Cai, Yan AU - Cai Y AD - State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Wei, Wen-Qiang AU - Wei WQ AD - Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. FAU - Hao, Jia-Jie AU - Hao JJ AD - State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: hjj8173@126.com. FAU - Wang, Ming-Rong AU - Wang MR AD - State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: wangmr2015@126.com. LA - eng PT - Journal Article DEP - 20240214 PL - United States TA - Transl Oncol JT - Translational oncology JID - 101472619 PMC - PMC10877408 OTO - NOTNLM OT - Esophageal squamous cell carcinoma OT - Nomogram model OT - Synergistic inhibition OT - Tenascin-C (TNC) COIS- Declaration of competing interest The authors declare that they have no conflict of interest. EDAT- 2024/02/15 00:42 MHDA- 2024/02/15 00:43 PMCR- 2024/02/14 CRDT- 2024/02/14 18:11 PHST- 2023/09/03 00:00 [received] PHST- 2024/01/01 00:00 [revised] PHST- 2024/01/22 00:00 [accepted] PHST- 2024/02/15 00:43 [medline] PHST- 2024/02/15 00:42 [pubmed] PHST- 2024/02/14 18:11 [entrez] PHST- 2024/02/14 00:00 [pmc-release] AID - S1936-5233(24)00014-7 [pii] AID - 101888 [pii] AID - 10.1016/j.tranon.2024.101888 [doi] PST - ppublish SO - Transl Oncol. 2024 Apr;42:101888. doi: 10.1016/j.tranon.2024.101888. Epub 2024 Feb 14.