Analysis of cancer-associated fibroblasts related genes identifies COL11A1 associated with lung adenocarcinoma prognosis

Sep 21, 2026

Background: Lung adenocarcinoma therapy remains challenging due to limited options, while cancer-associated fibroblasts (CAFs) are central to cancer development. This study aimed to identify a molecular target linked to CAFs for LUAD treatment. Methods: TCGA-LUAD data were analyzed to screen hub genes using EPIC and WGCNA, with additional databases and survival/differential expression validation. Functional enrichment and TISCH single-cell analysis clarified COL11A1 mechanisms, and immune-checkpoint correlations were assessed. Results: COL11A1 overexpression predicted poor prognosis, showing a 22% alteration frequency and CAF-dominant expression in the tumor microenvironment.

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Abstract

Background

Methods

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Introduction

Zheng et al. BMC Medical Genomics (2024) 17:97 BMC Medical Genomics [https://doi.org/10.1186/s12920-024-01863-1](https://doi.org/10.1186/s12920-024-01863-1) RESEARCH Open Access Analysis of cancer-associated fibroblasts related genes identifies COL11A1 associated with lung adenocarcinoma prognosis Haosheng Zheng 1,2†, Jian Tan 1,2†, Fei Qin 1,2†, Yuzhen Zheng 1,2, Xingping Yang 1,2, Xianyu Qin 1,2* and Hongying Liao 1,2* Abstract Background The treatment of lung adenocarcinoma is difficult due to the limited therapeutic options. Cancerassociated fibroblasts play an important role in the development of cancers. This study aimed to identify a promising molecular target associated with cancer-associated fibroblasts for the treatment of lung adenocarcinoma. Methods The Cancer Genome Atlas lung adenocarcinoma dataset was used to screen hub genes associated with cancer-associated fibroblasts via the EPIC algorithm and Weighted Gene Co-expression Network Analysis. Multiple databases were used together with our data to verify the differential expression and survival of COL11A1 . Functional enrichment analysis and the single-cell TISCH database were used to elucidate the mechanisms underlying COL11A1 expression. The correlation between COL11A1 and immune checkpoint genes in human cancers was also evaluated. Results Using the EPIC algorithm and Weighted Gene Co-expression Network Analysis, 13 hub genes associated with cancer-associated fibroblasts in lung adenocarcinoma were screened. Using the GEPIA database, Kaplan-Meier Plotter database, GSE72094, GSE75037, GSE32863, and our immunohistochemistry experiment data, we confirmed that COL11A1 overexpresses in lung adenocarcinoma and that high expression of COL11A1 is associated with a poor prognosis. COL11A1 has a genetic alteration frequency of 22% in patients with lung adenocarcinoma. COL11A1 is involved in the extracellular matrix activities of lung adenocarcinoma. Using theTISCH database, we found that COL11A1 is mainly expressed by cancer-associated fibroblasts in the tumor microenvironment rather than by lung adenocarcinoma cells. Finally, we found that COL11A1 is positively correlated with HAVCR2(TIM3), CD274 (PD-L1), CTLA4, and LAG3 in lung adenocarcinoma. Conclusion COL11A1 may be expressed and secreted by cancer-associated fibroblasts, and a high expression of COL11A1 may result inT cell exhaustion in the tumor microenvironment of lung adenocarcinoma. COL11A1 may serve as an attractive biomarker to provide new insights into cancer therapeutics. Keywords COL11A1, Lung adenocarcinoma, Immune checkpoint genes, WGCNA, Prognosis, Biomarker †Haosheng Zheng, JianTan and Fei Qin contributed equally to this work. *Correspondence: Xianyu Qin [qinxy27@mail.sysu.edu.cn](qinxy27@mail.sysu.edu.cn) Hongying Liao [liaohy2@mail.sysu.edu.cn](liaohy2@mail.sysu.edu.cn) 1Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, SunYat-sen University, Guangzhou, Guangdong, China 2Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://

FAQs

What was the study’s main goal regarding COL11A1 in lung adenocarcinoma?

To identify COL11A1 as a promising molecular target associated with cancer-associated fibroblasts, and evaluate its link to lung adenocarcinoma prognosis and treatment relevance.

Which computational methods and datasets were used to screen hub genes?

The study used TCGA lung adenocarcinoma data with the EPIC algorithm and Weighted Gene Co-expression Network Analysis (WGCNA) to identify hub genes related to cancer-associated fibroblasts.

What key clinical finding connects COL11A1 to lung adenocarcinoma prognosis?

High COL11A1 expression was confirmed to be associated with poor prognosis, and COL11A1 showed a genetic alteration frequency of 22% in LUAD patients.

Sep 21, 2026

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