Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34899841", "kind": "science-record", "revision": 4, "content_hash": "sha256:338d483cf6f0474d50e23e5ddb68aa17eacabdd9569e37f7124e951f52fa7bdb", "created_at": "2026-11-01T17:36:36Z", "updated_at": "2026-11-01T22:05:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer.", "doi": "10.3389/fgene.2021.755789", "pmid": "34899841", "authors": ["Xu-Tao Lin", "Qiu-Ning Wu", "Si Qin", "De-Jun Fan", "Min-Yi Lv", "Xi Chen", "Jia-Wei Cai", "Jing-Rong Weng", "Yi-Feng Zou", "Yu-Ming Rong", "Feng Gao"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Purpose: A certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-related gene (ATG) signature-based on high-throughput data analysis for disease-free survival (DFS) prognosis of patients with stage I/II CRC. Methods: Gene expression profiles and clinical information of CRC patients extracted from four public datasets were distributed to discovery and training cohort (GSE39582), validation cohort (TCGA CRC, n = 624), and meta-validation cohort (GSE37892 and GSE14333, n = 420). Autophagy genes significantly associated with prognosis were identified. Results: Among 655 autophagy-related genes, a 10-gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56-4.82]; p = 2.06 × 10-4), was constructed. The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15-4.55]; p = 1.5 × 10-2) and meta-validation cohorts (HR, 2.5[1.03-6.06]; p = 3.63 × 10-2) and proved to be prognostic in a multivariate analysis. Functional analysis revealed enrichment of several immune/inflammatory pathways in the high autophagy risk group, where increased infiltration of T regulatory cells (Tregs) and decreased infiltration of M1 macrophages were observed. Conclusion: Our study established a prognostic ATG signature that effectively predicted DFS for early-stage CRC patients. Meanwhile, the study also revealed the possible relationship among autophagy process, immune/inflammatory response, and tumorigenesis.", "claims": [{"id": "claim-method", "statement": "A Cox proportional hazard regression model on CRC samples together with the least absolute shrinkage and selection operator (LASSO) was applied to minimize the risk of overfitting as well as to generate a risk model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34899841", "locator": "sections[4] \"Construction of a Prognostic ATG Signature\" paragraph 2", "quote": "A Cox proportional hazard regression model on CRC samples together with the least absolute shrinkage and selection operator (LASSO) was applied to minimize the risk of overfitting as well as to generate a risk model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34899841", "locator": "sections[15] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A 10-gene ATG signature was constructed and was significantly associated with disease-free survival in early-stage colorectal cancer in the training, validation, and meta-validation cohorts.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34899841", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Among 655 autophagy-related genes, a 10-gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56–4.82]; p = 2.06 × 10–4), was constructed."}, {"asset": "source:pmid:34899841", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15–4.55]; p = 1.5 × 10–2) and meta-validation cohorts (HR, 2.5[1.03–6.06]; p = 3.63 × 10–2) and proved to be prognostic in a multivariate analysis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "A 10-gene ATG signature was constructed and was significantly associated with disease-free survival in early-stage colorectal cancer in the training, validation, and meta-validation cohorts.", "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:34899841"], "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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