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

Abstract

Background Papillary 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. Methods A 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. Results PRCC2 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%). Conclusions TPX2 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.

Bioinformatics analysis highlights CCNB1 as a potential prognostic biomarker and an anti-kidney renal papillary cell carcinoma drug target

“…This is consistent with the results of a previous study. [ 30 ] Subsequently, we constructed a line column predicting the 1-, 3-, and 5-year survival rates of patients with KIRP, and the results were encouraging. In addition, we conducted univariate and multivariate analyses of factors influencing KIRP prognosis.…”

“…This is consistent with the results of a previous study. [30] Subsequently, we constructed a line column The data was downloaded from the HPA database(https://www.proteinatlas.org/). The expression of CCNB1 was evaluated according to the intensity of the staining (0, 1+, 2+, and 3+) and the percentage of positive cells, which was scored as 0 (0%), 1 (1-25%), 2 (26-50%), 3 (51-75%) or 4 (76-100%).…”

MET Inhibitors for Papillary Renal Cell Carcinoma

“…These divisions largely represent differences in invasiveness and cost. Similarly, the biomarkers can also be thought of as single factor (IL-6 level, PDL-1 status), composite easily interpretable scores (Heng score, MSKCC score, Motzer score) and composite difficult to interpret scores (NGS biomarkers derived from PCA or machine learning) [42][43][44][45][46][47][48][49]. As these biomarkers develop, it will be important to consider both the ease with which they can be collected as well as their known relationship to drug or tumorigenesis/invasive pathways.…”

Bioinformatics analysis highlights CCNB1 as a potential prognostic biomarker and an anti-kidney renal papillary cell carcinoma drug target

“…In order to explore the interaction between CCNB1 and other genes, we established a co-expression analysis circle, in which TPX2, KIF20A, KIF11, CDK1, PBK, and KIFC1 showed the strongest positive correlation with CCNB1. A study has reported higher expression level of TPX2 was signi cantly associated with worse overall survival in Papillary renal cell carcinoma [31]. In another research, KIF20A knockdown can inhibit the proliferation and invasion of two kinds of renal carcinoma cell lines to a certain extent [32].…”