Harnessing lysosomal genetics: development of a risk stratification panel and unveiling of <i>DPP7</i> as a biomarker for colon adenocarcinoma

Zhengdong Luo; Yanlei Wang; Shunjie Zeng; Longchen Yu; Yuxiao Zhao; Hong Wang; Yingjing Fan; Yanli Zhang; Lili Wang; Yaping Li; Zhongfang Niu; Xin Zhang; Yi Zhang

doi:10.1016/j.jgg.2025.04.009

Volume 52 Issue 12

Dec. 2025

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Harnessing lysosomal genetics: development of a risk stratification panel and unveiling of DPP7 as a biomarker for colon adenocarcinoma

doi: 10.1016/j.jgg.2025.04.009

a. Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China;
b. Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan, Shandong 250012, China;
c. Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China;
d. Department of Anesthesiology, Yidu Central Hospital, Weifang Medical University, Qingzhou, Shandong 262500, China;
e. Department of Clinical Laboratory, Shandong Provincial Third Hospital, Jinan, Shandong 250000, China

Funds:

This work was supported by the Natural Science Foundation of Shandong Province (ZR2021MH110, ZR2020MH257, ZR2020MH323), the National Natural Science Foundation of China (82172339 and 82272410), Major Scientific and Technological Innovation Project of Shandong Province (2021CXGC010603 and 2021CXGC011105), and Taishan Scholar Program of Shandong Province (tstp20221156 and tsqn202306346).

Received Date: 2024-11-18
Accepted Date: 2025-04-12
Rev Recd Date: 2025-04-08
Publish Date: 2025-12-31

Abstract

Abstract

Lysosomal dysfunction has been implicated in the progression of colon adenocarcinoma (COAD), yet the prognostic significance and therapeutic potential of lysosome-related genes (LRGs) remain underexplored. In this study, we construct a 6-LRG-based prognostic risk stratification model (DPP7, ADAM8, CD1B, LRP2, ATP6V1C2, and PLAAT3) by integrating LASSO and Cox regression analyses. Stratifying patients based on median risk scores, we demonstrate that high-risk patients exhibit significantly worse clinical outcomes across the TCGA cohort and five independent GEO datasets. Furthermore, this panel outperforms 136 previously published models in terms of predictive accuracy for 1-, 3-, and 5-year survival rates. Validation multiplex immunofluorescence using an in-house tissue microarray cohort confirms that the 6-LRG signature serves as an independent prognostic factor. Additionally, high-risk patients exhibit distinct immunosuppressive tumor microenvironment and aggressive malignancy characteristics. Functional depletion of DPP7 significantly inhibits tumor cell proliferation, migration, and metastasis in both in vitro and in vivo settings. Moreover, DPP7 silencing attenuates epithelial-mesenchymal transition, as evidenced by the upregulation of E-cadherin and downregulation of N-cadherin, Vimentin, and Snail. In conclusion, this study establishes an LRG-based model for COAD prognostic prediction and nominates DPP7 as a promising therapeutic target for COAD treatment.
- Colon adenocarcinoma,
- Lysosome,
- Prognostic panel,
- DPP7,
- Immune microenvironment,
- Malignant features

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References(55)

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