Computational Recognition and Clinical Verification of TGF-β-Derived miRNA Signature With Potential Implications in Prognosis and Immunotherapy of Intrahepatic Cholangiocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34760703", "kind": "science-record", "revision": 4, "content_hash": "sha256:1ad4d1637f34840c432f8b38e77d67280647d948265f1382214128e1adf5ea7a", "created_at": "2026-11-01T17:36:27Z", "updated_at": "2026-11-01T22:05:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Computational Recognition and Clinical Verification of TGF-β-Derived miRNA Signature With Potential Implications in Prognosis and Immunotherapy of Intrahepatic Cholangiocarcinoma.", "doi": "10.3389/fonc.2021.757919", "pmid": "34760703", "authors": ["Zaoqu Liu", "Siyuan Weng", "Hui Xu", "Libo Wang", "Long Liu", "Yuyuan Zhang", "ChunGuang Guo", "Qin Dang", "Zhe Xing", "Taoyuan Lu", "Xinwei Han"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "MicroRNAs (miRNAs) were recently implicated in modifying the transforming growth factor β (TGF-β) signaling in multiple cancers. However, TGF-β-derived miRNAs and their potential clinical significance remain largely unexplored in intrahepatic cholangiocarcinoma (ICC). In this study, we proposed an integrated framework that enables the identification of TGF-β-derived miRNAs in ICC (termed \"TGFmitor\"). A total of 36 TGF-β-derived miRNAs were identified, of which nine significantly correlated with overall survival (OS) and aberrantly expressed in ICC. According to these miRNAs, we discovered and validated a TGF-β associated miRNA signature (TAMIS) in GSE53870 (n =63) and TCGA-CHOL (n =32). To further confirm the clinical interpretation of TAMIS, another validation based on qRT-PCR results from 181 ICC tissues was performed. TAMIS was proven to be an independent risk indicator for both OS and relapse-free survival (RFS). TAMIS also displayed robust performance in three cohorts, with satisfactory AUCs and C-index. Besides, patients with low TAMIS were characterized by superior levels of CD8+ T cells infiltration and PD-L1 expression, while patients with high TAMIS possessed enhanced CMTM6 expression. Kaplan-Meier analysis suggested CMTM6 could further stratify TAMIS. The TAMIShighCMTM6high subtype had the worst prognosis and lowest levels of CD8A and PD-L1 expression relative to the other subtypes, indicating this subtype might behave as \"super-cold\" tumors. Notably, the improved discrimination was observed when CMTM6 was combined with TAMIS. Overall, our signature could serve as a powerful tool to help improve prognostic management and immunotherapies of ICC patients.", "claims": [{"id": "claim-method", "statement": "To reveal the difference on Hallmark biological process between tumor and normal samples, we performed GSVA enrichment analysis via “GSVA” R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34760703", "locator": "sections[5] \"Gene Set Variation Analysis (GSVA)\" paragraph 2", "quote": "To reveal the difference on Hallmark biological process between tumor and normal samples, we performed GSVA enrichment analysis via “GSVA” R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Public data used in this work can be acquired from the TCGA Research Network portal (https://portal.gdc.cancer.gov/) and GSE53870 (http://www.ncbi.nlm.nih.gov/geo/). The raw experimental data supporting the conclusions of this article will be made available by the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34760703", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "Public data used in this work can be acquired from the TCGA Research Network portal (https://portal.gdc.cancer.gov/) and GSE53870 (http://www.ncbi.nlm.nih.gov/geo/). The raw experimental data supporting the conclusions of this article will be made available by the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TGF-β signaling was upregulated in intrahepatic cholangiocarcinoma and significantly associated with prognosis.", "kind": "quantitative", "target": {"value": 1.888, "unit": "hazard ratio", "tolerance": null, "source": "Further univariate Cox regression revealed the prognostic value of these pathways, and notably, only TGF-β signaling was significant (HR =1.888 [1.251-2.455], P =0.019) ( Figure 2B )."}, "evidence": [{"asset": "source:pmid:34760703", "locator": "sections[16] \"TGF-β Signaling Was Upregulated and Correlated With Prognosis in ICC\" paragraph 2", "quote": "Further univariate Cox regression revealed the prognostic value of these pathways, and notably, only TGF-β signaling was significant (HR =1.888 [1.251-2.455], P =0.019) ( Figure 2B )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "TGF-β signaling was upregulated in intrahepatic cholangiocarcinoma and significantly associated with prognosis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34760703"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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