STX4 as a potential biomarker for predicting prognosis and guiding clinical treatment decisions in clear cell renal cell carcinoma
Kai Zeng,
Qinyu Li,
Xi Wang,
Chaofan Liu,
Bingliang Chen,
Guoda Song,
Beining Li,
Bo Liu,
Xintao Gao,
Linli Zhang,
Jianping Miao
Affiliations
Kai Zeng
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Department of Urology, the First Affiliated Hospital of Shihezi University, Shihezi 832008, Xinjiang, China
Qinyu Li
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
Xi Wang
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
Chaofan Liu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
Bingliang Chen
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
Guoda Song
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
Beining Li
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
Bo Liu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
Xintao Gao
Department of Urology, Sir RunRun Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China; Corresponding author.
Linli Zhang
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Corresponding author.
Jianping Miao
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Corresponding author.
Clear cell renal cell carcinoma (ccRCC) represents a frequent subtype of kidney cancer, with the prognosis remaining poor for individuals with metastatic disease. Given its resistance to both radiation and chemotherapy, targeted therapies and immunotherapies have emerged as critical for effective ccRCC treatment. Within this context, the SNARE protein STX4, which is associated with malignant cancer cell migration, provides a promising focus. The underlying mechanism, however, requires further illumination. Furthermore, the influence of STX4 on the ccRCC tumor microenvironment remains to be determined. In our research, we utilized multiple databases and immunohistochemical staining to confirm differential STX4 expression and its prognostic implications. We evaluated the potential tumor-promoting function of STX4 in ccRCC cell lines through molecular studies. Additionally, we conducted functional enrichment analysis to delve deeper into the underlying mechanisms and performed immune infiltration and drug sensitivity analyses to assess the potential of STX4 as a prognostic biomarker and therapeutic target. Our study reveals that STX4 contributes to cancer progression by enhancing AKT expression and stimulating the activation of VEGF signaling pathways. Additionally, STX4 further fosters CD8+ T-cell infiltration and diminishes the percentage of CAFs and M2-TAMs. Our findings suggest that patients presenting higher STX4 levels may exhibit enhanced responsiveness to immunotherapy and higher sensitivity to the medications axitinib and everolimus. Finally, we propose STX4 expression assessment as a novel approach to predict patient response to respective immunotherapies and targeted treatments, hence potentially improving patient outcomes.
