[Molecular characteristics for poor prognosis related renal cell carcinoma with lymph metastases]

Next-generation sequencing (NGS) technology was used to analyze the gene mutation profile of lymph node metastases in renal cell carcinoma, and the molecular characteristics associated with poor prognosis were found, providing new ideas for mechanism research and treatment.

Retrospective clinical data collection was conducted on 31 patients with lymphoid metastatic renal cell carcinoma and 21 patients with non-metastatic renal cell carcinoma. A total of 81 formalin-fixed paraffin-embedded tissue samples were retrieved from the Department of Pathology, including primary tumor, lymph node metastasis, and distant metastasis samples. The gene mutation profiles of the patients were examined using next-generation sequencing technology. The patients were followed up to analyze the correlation between lymph node metastasis and patient prognosis.

The lymph node metastasis group showed differences in tumor size (P=0.006), World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (P=0.002), T stage (P=0.003) and tumor thrombus (P=0.025) compared with non-metastatic renal cell carcinoma. The most commonly mutated genes in our cohort were the tumor suppressor genes VHL (38%), PBRM1 (22%), and SETD2 (20%). More-over, copy number variations were associated with tumor metastasis, and some mutation features were highly similar to known mutation patterns. There was a difference in mutation frequency between the patients in the metastasis group and samples in the non-metastasis group. The mutation frequency of most genes in the metastasis group was higher, however, Reactome pathway enrichment analysis did not show statistically significant differences in the shared enriched pathways between the two groups. There was a strong degree of concordance between the tumor' s primary and metastatic foci in the same patient, and genomic indicators [such as purity, ploidy, weighted-genomic integrity index (WGII), and intra-tumor heterogeneity (ITH)] as well as clonal and subclonal composition analysis further supported this consistency. The overall survival (OS) was higher in the patients without metastases (P=0.041), and specific gene mutations (such as IGF2R, JUN, EPHA5, and FH) were associated with poorer prognosis. To facilitate distant metastasis, lymph nodes might function as a "metastatic pool".

The multigene NGS evaluates multiple relevant markers simultaneously, revealing several genetic alterations in the patients with lymphatic metastatic renal cell carcinorma. NGS-based molecular analysis can assist clinicians in assessing a patient' s prognosis and identifying novel, potentially therapeutic mechanisms.