Identification of prognostic and therapeutic biomarkers in type 2 papillary renal cell carcinoma

作者全名："Wang, Yue; Tian, Xi; Zhu, Shu-Xuan; Xu, Wen-Hao; Anwaier, Aihetaimujiang; Su, Jia-Qi; Gan, Hua-Lei; Qu, Yuan-Yuan; Zhao, Jian-Yuan; Zhang, Hai-Liang; Ye, Ding-Wei"

作者地址："[Wang, Yue; Tian, Xi; Xu, Wen-Hao; Anwaier, Aihetaimujiang; Su, Jia-Qi; Qu, Yuan-Yuan; Zhao, Jian-Yuan; Zhang, Hai-Liang; Ye, Ding-Wei] Fudan Univ, Shanghai Canc Ctr, Collaborat Innovat Ctr Genet & Dev, Sch Life Sci,Dept Urol,State Key Lab Genet Engn, Shanghai 200433, Peoples R China; [Wang, Yue; Tian, Xi; Xu, Wen-Hao; Anwaier, Aihetaimujiang; Su, Jia-Qi; Gan, Hua-Lei; Qu, Yuan-Yuan; Zhang, Hai-Liang; Ye, Ding-Wei] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 20032, Peoples R China; [Zhu, Shu-Xuan] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing 400016, Peoples R China; [Gan, Hua-Lei] Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai 200032, Peoples R China"

通信作者："Qu, YY; Zhao, JY; Zhang, HL; Ye, DW (通讯作者)，Fudan Univ, Shanghai Canc Ctr, Collaborat Innovat Ctr Genet & Dev, Sch Life Sci,Dept Urol,State Key Lab Genet Engn, Shanghai 200433, Peoples R China.; Qu, YY; Zhang, HL; Ye, DW (通讯作者)，Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 20032, Peoples R China."

来源：WORLD JOURNAL OF SURGICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000952249100001

JCR分区：Q1

影响因子：2.5

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Type 2 papillary renal cell carcinoma; Prognosis; mTOR inhibitor; Biomarker

摘要："BackgroundPapillary renal cell carcinoma (PRCC) can be divided into type 1 (PRCC1) and type 2 (PRCC2) and PRCC2 share a more invasive phenotype and worse prognosis. This study aims to identify potential prognostic and therapeutic biomarkers in PRCC2.MethodsA cohort from The Cancer Genome Atlas and two datasets from Gene Expression Omnibus were examined. Common differentially expressed genes (DEGs) were screened and potential biomarkers were explored by using Kaplan-Meier method and cox regression analysis. Functional enrichment analysis was utilized to evaluate the potential biological functions. Tumor infiltrating immune cells were estimated by CIBERSORT algorithm. Ninety-two PRCC2 samples from Fudan University Shanghai Cancer Center were obtained, and immunostaining was performed to validate prognostic and therapeutic significance of the potential biomarker.ResultsPRCC2 has worse overall survival and shares distinct molecular characteristics from PRCC1. There was significant higher expression level of Targeting protein for Xklp2 (TPX2) in PRCC2 compared with normal tissues. Higher expression level of TPX2 was significantly associated with worse overall survival in PRCC2 and kinesin family genes expression were found significantly elevated in high risk PRCC2. Abundance of tumor infiltrating M1 macrophage was significantly higher in PRCC2 and it was also associated with worse overall survival. In the FUSCC cohort, higher TPX2 expression was significantly correlated with worse overall and progression-free survival. Retrospective analysis indicated that mTOR inhibitor (everolimus) had greater efficacy in the high-risk group than in the low-risk group (overall response rate: 28.6% vs. 16.7%) and that everolimus had greater efficacy than sunitinib in the high-risk group (overall response rate: 28.6% vs. 20%).ConclusionsTPX2 was a prognostic and therapeutic biomarker in PRCC2. Higher abundance of tumor infiltrating M1 macrophage was significantly associated with worse overall survival in PRCC2. mTOR inhibitors may have good efficacy in patients with high-risk PRCC2."

基金机构："National Key Research and Development Program of China [2019YFC1316005]; National Natural Science Foundation of China [81772706, 81802525, 81902568]; Shanghai Science and Technology Committee [20ZR1413100, 18511108000]; Shanghai Sailing Program [19YF1409700]"

基金资助正文："This work is supported by Grants from the National Key Research and Development Program of China (No.2019YFC1316005), National Natural Science Foundation of China (No.81772706, No.81802525 and No.81902568), Shanghai Science and Technology Committee (No.20ZR1413100, No.18511108000), and Shanghai Sailing Program (No.19YF1409700)."