Investig Clin Urol.  2022 Nov;63(6):602-611. 10.4111/icu.20210341.

A retrospective single-centered, comprehensive targeted genetic sequencing analysis of prognostic survival using tissues from Korean patients with metastatic renal cell carcinoma after targeted therapy

• Kim SH
• Park J
• Park WS
• Hong D
• Chung J

• KMID: 2534615
• DOI: http://doi.org/10.4111/icu.20210341

Abstract

Purpose
To identify candidate gene mutations to significantly predict the risk of survival prognosis after treatment with systemic first-line targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) patients.
Materials and Methods
Between 2005 and 2017, 168 triplet-tissue block samples from 56 mRCC patients were selected for targeted gene sequencing (TGS). Fifty-six patients’ medical records including overall survival (OS) and progression-free survival (PFS) at the time of mRCC diagnosis were evaluated. The patients were grouped into favorable (>12 months/>3 years), intermediate (3– 12/12–36 months), and poor groups according to their PFS/OS (<3 months/<12 months). We identified any significant therapeutic targeted genes relating to the survival with a significance at p<0.050.
Results
The first line therapeutic response showed 1.8% complete remission, 14.2% partial response, 42.9% stable disease, and 41.1% progressive disease. Among the overall TGS results, the cumulative effect of CDH1 , and/or PTK2 genes significantly reflected the therapeutic responses in terms of PFS/OS; CDH1 and PTK2 mutations were associated with poor prognostic outcomes (p<0.050). Among only triplet-quality check passed tissues, the SGO2 , BRAF , URB1 , and NEDD1 mutated genes significantly correlated with OS. Regarding metastasis, patients with liver metastasis had the worst OS (p=0.050). The combinational mutation number from these two candidate genes in the liver metastatic samples with mutated EGFR2 and FABP7 also showed a significantly worse OS than those with other metastatic lesions (p<0.050).
Conclusions
This study reports several significant mutated genes related to the survival prognosis in mRCC patients treated with first-line TT.

Keyword

Cancer mutated gene; Clear-cell metastatic renal cell carcinoma; Overall survivals; Targeted gene sequencing; Targeted therapy