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已发表论文
由自噬和肝转移相关特征构成的结直肠癌新型预后特征：bulk 和单细胞转录组数据的综合分析
Authors Bai B , Cui Y, Zhong X, Zhu B, Meng Z , Chen L, Di L, Huang L, Wang J, Jin Z, Lu X, Zhou B
Received 17 September 2025
Accepted for publication 13 January 2026
Published 6 February 2026 Volume 2026:15 563779
DOI https://doi.org/10.2147/ITT.S563779
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Michael Shurin
Binglong Bai,1,* Yuekai Cui,2,* Xihao Zhong,1,* Bingzi Zhu,2 Ziqi Meng,3 Letian Chen,2 Leyan Di,4 Linjing Huang,5 Jisheng Wang,1 Zhouxiang Jin,1 Xufeng Lu,2,6 Bin Zhou1
1Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2Department of Gastrointestinal Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Anorectal Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 4Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 6Research Center of Basic Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Bin Zhou, Email pzhoubin@126.com Xufeng Lu, Email luxufeng@wmu.edu.cn
Background: Colorectal cancer (CRC) is a highly aggressive malignancy prone to liver metastasis, which significantly worsens prognosis of patients. Autophagy supports tumor cell survival by meeting metabolic demands and evading programmed cell death. This study aimed to develop a prognostic risk signature for CRC patients by integrating autophagy- and metastasis-related genes and to investigate its association with the tumor immune microenvironment and implications for immunotherapy.
Methods: Weighted gene co-expression network analysis (WGCNA) identified candidate genes related to autophagy and liver metastasis. Univariate Cox and LASSO regression analyses were employed to develop a risk signature in the TCGA cohort, which was subsequently validated using an independent GEO cohort. Functional enrichment, immune infiltration, the heterogeneity and dynamics of macrophages and CD8+ T cells, and cell–cell communication were analyzed. The expression patterns of key genes were confirmed through Western blotting and immunohistochemistry.
Results: A prognostic risk signature incorporating six biomarkers (SPP1, JCHAIN, DNASE1L3, SNAI1, TPM1, and FKBP10) was developed and confirmed. The risk signature was an independent prognosticator and outperformed traditional prognostic factors. The patients in high-risk group exhibited heightened Tumor Immune Dysfunction and Exclusion (TIDE) scores, indicating a potential for immunotherapy resistance. Furthermore, enhanced autophagy and metastatic activity were accompanied by differentiation of macrophages toward an SPP1+ M2-like phenotype and of CD8+ T cells toward an exhausted state. Experimental validation confirmed that SPP1, SNAI1, and FKBP10 were highly expressed in CRC tissues.
Conclusion: In our study, we developed and validated a novel autophagy- and liver metastasis-associated prognostic signature for CRC. The risk signature effectively predicts alterations in the tumor immune microenvironment, immunotherapy, chemotherapy sensitivity and intercellular communication across different risk groups. Importantly, our findings reveal that autophagy and liver metastasis synergistically foster an immunosuppressive microenvironment, highlighting a potential target for therapeutic intervention.
Keywords: colorectal cancer, autophagy, liver metastasis, tumor immune microenvironment, cell-cell communication
1Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2Department of Gastrointestinal Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Anorectal Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 4Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 6Research Center of Basic Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Bin Zhou, Email pzhoubin@126.com Xufeng Lu, Email luxufeng@wmu.edu.cn
Background: Colorectal cancer (CRC) is a highly aggressive malignancy prone to liver metastasis, which significantly worsens prognosis of patients. Autophagy supports tumor cell survival by meeting metabolic demands and evading programmed cell death. This study aimed to develop a prognostic risk signature for CRC patients by integrating autophagy- and metastasis-related genes and to investigate its association with the tumor immune microenvironment and implications for immunotherapy.
Methods: Weighted gene co-expression network analysis (WGCNA) identified candidate genes related to autophagy and liver metastasis. Univariate Cox and LASSO regression analyses were employed to develop a risk signature in the TCGA cohort, which was subsequently validated using an independent GEO cohort. Functional enrichment, immune infiltration, the heterogeneity and dynamics of macrophages and CD8+ T cells, and cell–cell communication were analyzed. The expression patterns of key genes were confirmed through Western blotting and immunohistochemistry.
Results: A prognostic risk signature incorporating six biomarkers (SPP1, JCHAIN, DNASE1L3, SNAI1, TPM1, and FKBP10) was developed and confirmed. The risk signature was an independent prognosticator and outperformed traditional prognostic factors. The patients in high-risk group exhibited heightened Tumor Immune Dysfunction and Exclusion (TIDE) scores, indicating a potential for immunotherapy resistance. Furthermore, enhanced autophagy and metastatic activity were accompanied by differentiation of macrophages toward an SPP1+ M2-like phenotype and of CD8+ T cells toward an exhausted state. Experimental validation confirmed that SPP1, SNAI1, and FKBP10 were highly expressed in CRC tissues.
Conclusion: In our study, we developed and validated a novel autophagy- and liver metastasis-associated prognostic signature for CRC. The risk signature effectively predicts alterations in the tumor immune microenvironment, immunotherapy, chemotherapy sensitivity and intercellular communication across different risk groups. Importantly, our findings reveal that autophagy and liver metastasis synergistically foster an immunosuppressive microenvironment, highlighting a potential target for therapeutic intervention.
Keywords: colorectal cancer, autophagy, liver metastasis, tumor immune microenvironment, cell-cell communication