Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinoma

It has been well established that tumor-infiltrating lymphocytes (TILs) play a critical role in the pathogenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the mechanism on the interactions between TILs and tumor cells in the tumor-immune microenvironment remains unclear. I...

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Main Authors: Lingling Li, Xiaocui Bu, Shuhui Wang, Yan Liu, Chongdao Chen, Wei Zhang, Peng Zhao
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523324003747
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author Lingling Li
Xiaocui Bu
Shuhui Wang
Yan Liu
Chongdao Chen
Wei Zhang
Peng Zhao
author_facet Lingling Li
Xiaocui Bu
Shuhui Wang
Yan Liu
Chongdao Chen
Wei Zhang
Peng Zhao
author_sort Lingling Li
collection DOAJ
description It has been well established that tumor-infiltrating lymphocytes (TILs) play a critical role in the pathogenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the mechanism on the interactions between TILs and tumor cells in the tumor-immune microenvironment remains unclear. In the present study, the expression of Response Gene to Complement 32 (RGC-32) was evaluated using immunohistochemistry. We analyzed the associations of RGC-32 expression with patient characteristics and survival. We also assessed TILs and their subsets (CD3+, CD4+, CD8+ and PD-1+) in the tumor nest. The level of RGC-32 expression was positively correlated with ISUP grade and Ki67 expression and was an independent poor prognosis factor of patients with ccRCC. RGC-32 expression was negatively correlated with the infiltration of TIL and CD3+T cells, but positively correlated with infiltration of PD-1+cells. In vitro studies showed that RGC-32 expression in renal cancer cells was downregulated by activated immune cells. Further investigation revealed that RGC-32 expression in renal cancer cells was inhibited by TNF-α and IL-1β secreted by activated immune cells. Collectively, these data indicate that RGC-32 could be a novel prognostic and druggable target related to the tumor-immune microenvironment in renal cancer.
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publishDate 2025-02-01
publisher Elsevier
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series Translational Oncology
spelling doaj-art-3ffb49459fc44b3997cf827d8567bca42025-01-22T05:41:28ZengElsevierTranslational Oncology1936-52332025-02-0152102248Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinomaLingling Li0Xiaocui Bu1Shuhui Wang2Yan Liu3Chongdao Chen4Wei Zhang5Peng Zhao6School of Basic Medicine, Shandong Second Medical University, Weifang, ChinaThe Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, ChinaClinical laboratory, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, ChinaDepartment of Pathology, The 971 Hospital of People's Liberation Army Navy, Qingdao, ChinaDepartment of Pathology, The 971 Hospital of People's Liberation Army Navy, Qingdao, ChinaDepartment of Pathology, The 971 Hospital of People's Liberation Army Navy, Qingdao, China; Corresponding author.Biotherapy Center, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China; Corresponding author.It has been well established that tumor-infiltrating lymphocytes (TILs) play a critical role in the pathogenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the mechanism on the interactions between TILs and tumor cells in the tumor-immune microenvironment remains unclear. In the present study, the expression of Response Gene to Complement 32 (RGC-32) was evaluated using immunohistochemistry. We analyzed the associations of RGC-32 expression with patient characteristics and survival. We also assessed TILs and their subsets (CD3+, CD4+, CD8+ and PD-1+) in the tumor nest. The level of RGC-32 expression was positively correlated with ISUP grade and Ki67 expression and was an independent poor prognosis factor of patients with ccRCC. RGC-32 expression was negatively correlated with the infiltration of TIL and CD3+T cells, but positively correlated with infiltration of PD-1+cells. In vitro studies showed that RGC-32 expression in renal cancer cells was downregulated by activated immune cells. Further investigation revealed that RGC-32 expression in renal cancer cells was inhibited by TNF-α and IL-1β secreted by activated immune cells. Collectively, these data indicate that RGC-32 could be a novel prognostic and druggable target related to the tumor-immune microenvironment in renal cancer.http://www.sciencedirect.com/science/article/pii/S1936523324003747Renal cancerRGC-32Tumor-immune microenvironmentTumor infiltrating lymphocytesInflammatory cytokines
spellingShingle Lingling Li
Xiaocui Bu
Shuhui Wang
Yan Liu
Chongdao Chen
Wei Zhang
Peng Zhao
Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinoma
Translational Oncology
Renal cancer
RGC-32
Tumor-immune microenvironment
Tumor infiltrating lymphocytes
Inflammatory cytokines
title Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinoma
title_full Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinoma
title_fullStr Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinoma
title_full_unstemmed Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinoma
title_short Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinoma
title_sort response gene to complement 32 is associated with poor patient survival and an inflamed tumor immune microenvironment in clear cell renal cell carcinoma
topic Renal cancer
RGC-32
Tumor-immune microenvironment
Tumor infiltrating lymphocytes
Inflammatory cytokines
url http://www.sciencedirect.com/science/article/pii/S1936523324003747
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