Proteomic analysis identifies HMGA2 as a novel biomarker of overall survival in papillary renal cell carcinoma.

ABSTRACT

PURPOSE: Although papillary renal cell carcinoma (PRCC) has a relatively favorable prognosis, a small number of patients with lymph node or distant metastasis have a poor prognosis. Owing to the complex typing and heterogeneity of PRCC, it remains difficult to provide risk stratification. The objective of our research was to identify potential markers of PRCC prognosis. METHODS: We performed proteomics and bioinformatics analyses on six pairs of formalin-fixed paraffin-embedded tumor and paired normal tissue samples. The Cancer Genome Atlas (TCGA) data were used to analyze the prognostic value of differentially expressed proteins (DEPs) in PRCC. We verified the expression of the major biomarker through immunohistochemistry (IHC) in 91 PRCC tumor specimens. RESULTS: Proteomic analysis revealed 1544 DEPs between tumor and paired normal tissues. PRCC transcriptomic data from the TCGA database revealed that compared to non-tumor tissues, the expression of high-mobility group protein A2 (HMGA2) was upregulated in tumor tissues, and patients with high HMGA2 expression exhibited shorter overall survival times. HMGA2 was associated with PRCC tissue subtype and higher cell pleomorphism. Both TCGA and IHC results showed that HMGA2 expression was associated with lymph node metastasis and clinical stage. CONCLUSION: HMGA2 was positively correlated with malignant progression and could be a valuable novel prognostic biomarker for PRCC risk stratification.