Mining bone metastasis related key genes of prostate cancer from the STING pathway based on machine learning

作者全名：Li, Guiqiang; Zhao, Runhan; Xie, Zhou; Qu, Xiao; Duan, Yingtao; Zhu, Yafei; Liang, Hao; Tang, Dagang; Li, Zefang; He, Weiyang

作者地址：[Li, Guiqiang; He, Weiyang] Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing, Peoples R China; [Li, Guiqiang] Chongqing Tradit Chinese Med Hosp, Dept Urol, Chongqing, Peoples R China; [Zhao, Runhan; Xie, Zhou; Qu, Xiao; Duan, Yingtao; Zhu, Yafei; Liang, Hao; Tang, Dagang; Li, Zefang] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing, Peoples R China; [Tang, Dagang] Chongqing Tradit Chinese Med Hosp, Dept Orthoped, Chongqing, Peoples R China; [Li, Zefang] Chongqing Univ, Qianjiang Hosp, Dept Orthoped, Chongqing, Peoples R China

通信作者：He, WY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing, Peoples R China.; Tang, DG; Li, ZF (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing, Peoples R China.; Tang, DG (通讯作者)，Chongqing Tradit Chinese Med Hosp, Dept Orthoped, Chongqing, Peoples R China.; Li, ZF (通讯作者)，Chongqing Univ, Qianjiang Hosp, Dept Orthoped, Chongqing, Peoples R China.

来源：FRONTIERS IN MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001237526100001

JCR分区：Q1

影响因子：3.1

年份：2024

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：prostate cancer; bone metastasis; random forest; STING; nomogram

摘要：Background Prostate cancer (PCa) is the second most prevalent malignant tumor in male, and bone metastasis occurs in about 70% of patients with advanced disease. The STING pathway, an innate immune signaling mechanism, has been shown to play a key role in tumorigenesis, metastasis, and cancerous bone pain. Hence, exploring regulatory mechanism of STING in PCa bone metastasis will bring novel opportunities for treating PCa bone metastasis.Methods First, key genes were screened from STING-related genes (SRGs) based on random forest algorithm and their predictive performance was evaluated. Subsequently, a comprehensive analysis of key genes was performed to explore their roles in prostate carcinogenesis, metastasis and tumor immunity. Next, cellular experiments were performed to verify the role of RELA in proliferation and migration in PCa cells, meanwhile, based on immunohistochemistry, we verified the difference of RELA expression between PCa primary foci and bone metastasis. Finally, based on the key genes to construct an accurate and reliable nomogram, and mined targeting drugs of key genes.Results In this study, three key genes for bone metastasis were mined from SRGs based on the random forest algorithm. Evaluation analysis showed that the key genes had excellent prediction performance, and it also showed that the key genes played a key role in carcinogenesis, metastasis and tumor immunity in PCa by comprehensive analysis. In addition, cellular experiments and immunohistochemistry confirmed that overexpression of RELA significantly inhibited the proliferation and migration of PCa cells, and RELA was significantly low-expression in bone metastasis. Finally, the constructed nomogram showed excellent predictive performance in Receiver Operating Characteristic (ROC, AUC = 0.99) curve, calibration curve, and Decision Curve Analysis (DCA) curve; and the targeted drugs showed good molecular docking effects.Conclusion In sum, this study not only provides a new theoretical basis for the mechanism of PCa bone metastasis, but also provides novel therapeutic targets and novel diagnostic tools for advanced PCa treatment.

基金机构：Fundamental Research Funds for the Central Universities [2022CDJYGRH-019]

基金资助正文：The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by Fundamental Research Funds for the Central Universities (Grant NO. 2022CDJYGRH-019).