Gene mutation profiling and clinical significances in patients with renal cell carcinoma

Wang, Yongquan; He, Peng; Zhou, Xiaozhou; Wang, Cong; Fu, Jian; Zhang, Dawei; Liao, Deyang; Zhou, Zhansong; Wu, Chunman; Gong, Wei

doi:10.1016/j.clinsp.2023.100259

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Sumário

Original articles • Clinics 78 • 2023 • https://doi.org/10.1016/j.clinsp.2023.100259 copy

Gene mutation profiling and clinical significances in patients with renal cell carcinoma

Authorship SCIMAGO INSTITUTIONS RANKINGS

Highlights

EGFR, POLE, and PB1 genes had high mutated frequency in the patients with relapse and metastatic cancer.
PBRM1, BAP1, KDM5C, and BAP1 genes were critical for the overall survival.
Wild-type PBRM1 and mutated BAP1 were key indications for the predication of OS.

Abstract

Objectives

The pathological mechanisms of patients with Renal Cell Carcinoma (RCC) remain defined. This study aimed to evaluate relationships between the landscape of gene mutations and their clinical significance in RCC patients.

Methods

Tissue and peripheral blood samples of 42 patients with RCC were collected and performed for the Next Generation Sequencing (NGS) with Geneseeq PrimeTM 425-gene panel probes. Their landscapes of gene mutation were analyzed. We also carried out an evaluation of Tumor-Node-Metastasis (TNM) staging, RENAL nephelometry score, surgery, and targeted drug treatment of patients. Then we compared the correlations of landscape in gene mutations and the prognosis.

Results

The most common gene alternations, including BAP1, PBRM1, SETD2, CSF1R, NPM1, EGFR, POLE, RB1, and VHL genes, were identified in tissue and blood samples of 75% of patients. EGFR, POLE, and RB1 gene mutations frequently occurred in relapsed and metastatic patients. BAP1, CCND2, KRAS, PTPN11, ERBB2/3, JAK2, and POLE were presented in the patients with > 9 RENAL nephelometry score. Univariable analysis indicated that SETD2, BAP1, and PBRM1 genes were key factors for Disease-Free Survival (DFS). Multivariable analysis confirmed that mutated SETD1, NPM1, and CSF1R were critical factors for the Progression Free Survival (PFS) of RCC patients with target therapy.

Conclusions

Wild-type PBRM1 and mutated BAP1 in patients with RCC were strongly associated with the outcomes of the patient. The PFS of the patients with SETD2, NPM1, and CSF1R mutations were significantly shorter than those patients without variants.

Keywords
BAP1; Next generation sequences; Overall survival; PBRM1; Renal cell carcinoma; Renal score

	Number of Cases	χ2	p-values
Age		1.32	0.87
> 60-year-old	20 (47.6%)
≤ 60-year-old	22 (52.4%)
Gender		0.04	0.02
Female	14 (33.3%)
Male	28 (66.7%)
Pathological subtype		12.53	0.001
ccRCC	26 (61.9%)
pRCC	4 (9.5%)
chRCC	4 (9.5%)
evRCC	4 (9.5%)
RCC with Mit family translocation	4 (9.5%)
Renal Score		10.25	0.001
> 9	15 (35.7%)
≤ 9	27 (64.3%)
Surgery		13.25	0.002
Yes	30 (71.4%)
No	12 (28.6%)
Targeted drug use		1.54	0.97
Ye	21 (50%)
No	21 (50%)

Gene names	HR (95% CI for HR)	Log-rank_ p-value
SEX_ group	0 (0-Inf)	0.008
CSF1R_CNV	3598241712.414 (0-Inf)	0.008
NPM1_CNV	3598241712.414 (0-Inf)	0.008
BRCA2_SNV	4262925654.7 (0-Inf)	0.008
FAT1_SNV	3598241712.414 (0-Inf)	0.008
CCND2_CNV	3598241712.414 (0-Inf)	0.008
PTPN11_CNV	3598241712.414 (0-Inf)	0.008
ARID1A_SNV	3598241712.414 (0-Inf)	0.008
ERBB3_CNV	3598241712.414 (0-Inf)	0.008
KRAS_CNV	3598241712.414 (0-Inf)	0.008
PRDM1_SNV	3598241712.414 (0-Inf)	0.008
SETD2_SNV	3598241712.414 (0-Inf)	0.008
RICTOR_SNV	3598241712.414 (0-Inf)	0.008
AR_SNV	3598241712.414 (0-Inf)	0.008
CDH1_SNV	3598241712.414 (0-Inf)	0.008
CDK6_SNV	3598241712.414 (0-Inf)	0.008
ETV1_SNV	3598241712.414 (0-Inf)	0.008

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E-mail: clinics@hc.fm.usp.br

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[1] * Corresponding author. E-mail address:gongwei0851@aliyun.com (W. Gong).