Tissue Proteomics of Feline Mammary Carcinoma: Identification of Potential Biomarkers Based on Metastatic Status and Histopathological Characteristics

Abstract

Feline mammary carcinoma (FMC) is a prevalent and aggressive cancer with high metastatic potential. Few tissue biomarkers have been reported to help evaluate disease progression in FMC. This study aimed to analyze the tissue proteomic profiles of metastatic feline mammary carcinoma (mFMC) and non-metastatic FMC (NmFMC) across various histological grades (HGs) and histological types (HTs) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tissue samples were collected from 13 NmFMC, 26 mFMC, and 13 healthy controls (CTRL). Samples were trypsinized and subjected to LC-MS/MS. Proteome results were analyzed based on the metastatic status, HGs, and HTs of the samples. The findings revealed a total of 16,897 expressed proteins were identified. Among these, upregulations of interleukin 18 receptor 1 (IL18R1) and rRNA adenine N(6)-methyltransferase (DIMT1) were commonly observed in all mFMC, HG III and solid HT groups, whereas immunoglobulin heavy chain variable (IGHV), phenylalanine-tRNA ligase (FARS2) and gasdermin C (GSDMC) were markedly increased in mFMC and solid HT groups, compared with NmFMC and CTRL. Notably, H1.5 linker histone, cluster member (H1.5) expression showed a significant difference between mFMC and NmFMC in Kaplan–Meier survival analysis (P < 0.01). Conversely, the tumor suppressor, NOP14 nucleolar protein (NOP14), and sodium channel protein (SCN8A) were downregulated in mFMC, HG III, and solid HT groups (P < 0.01). In summary, this study identified potential tumor markers and tumor suppressor candidates for FMC using LC-MS/MS. Further exploration is needed to evaluate the feasibility of utilizing these protein markers in a clinical setting with a larger cohort.