J Cancer 2021; 12(8):2243-2257. doi:10.7150/jca.48664

Research Paper

MMP9 and IGFBP1 Regulate Tumor Immune and Drive Tumor Progression in Clear Cell Renal Cell Carcinoma

Tianbo Xu1*, Su Gao2,3*, Jingchong Liu1*, Yu Huang1, Ke Chen1, Xiaoping Zhang1✉

1. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
2. Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
3. Institute of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
* These authors contributed equally to this work.

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Citation:
Xu T, Gao S, Liu J, Huang Y, Chen K, Zhang X. MMP9 and IGFBP1 Regulate Tumor Immune and Drive Tumor Progression in Clear Cell Renal Cell Carcinoma. J Cancer 2021; 12(8):2243-2257. doi:10.7150/jca.48664. Available from https://www.jcancer.org/v12p2243.htm

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Abstract

Immunotherapy is a novel approach and has been used in various diseases, especially in cancers. Recently, immunotherapy has gradually been used to treat advanced clear cell renal cell carcinoma (ccRCC) or metastatic ccRCC. However, the efficacy of immunotherapy is not satisfying due to the influence of the tumor microenvironment. In this study, we mainly focused on the abundance and function of tumor-infiltrating immune cells (TIICs). Monocyte and TNM stage were identified as independent prognostic factors via CIBERSORT and Cox regression analysis. Then, ccRCC patients were divided into high risk/TNMhighMonocyteslow cluster and low risk/TNMlowMonocyteshigh cluster. Further differential gene analysis, protein-protein interaction (PPI) network, and survival analysis screened nine hub genes between the above two clusters. MMP9 and IGFBP1 were selected for further study through sample validation. Moreover, gene set enrichment analysis revealed that MMP9 and IGFBP1 were involved in tumor immune via mediating cell surface receptor signal pathway, cytokine production pathway, or monocyte signal pathway. In conclusion, these findings suggested that monocyte acted as a protective factor and MMP9/IGFBP1 played a vital role in tumor immune, which might become potential novel biomarkers and therapeutic targets for immunotherapy in ccRCC.

Keywords: clear cell renal cell carcinoma, MMP9, IGFBP1, biomarker, tumor-infiltrating immune cells