Alpha-2-Macroglobulin and Alpha-2-HS Glycoprotein are Potential Markers of Renal Cell Carcinoma: An Insight from Proteome Profile of Cancer Tissues
Alpha-2-Macroglobulin and Alpha-2-HS Glycoprotein are Potential Markers of Renal Cell Carcinoma: An Insight from Proteome Profile of Cancer Tissues
Safa Akhtar1,3, Shahzadi Noreen2, Anna E. Lokshin3 and Muhammad Waheed Akhtar1*
ABSTRACT
Renal cell carcinoma (RCC) is characterized as the most common neoplasm of the human kidney among the top fifteen most diagnosed tumors, encompassing multiple subhistologies with definite genomic, clinicopathological, genomic and proteomic features. Proteomics technologies enable the detection and quantitation of protein profiles associated with RCC to delineate the dysregulated expression of various proteins involved in multiple cellular processes. In this study, which is novel for local population, we employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to characterize proteome profiles of the tissue and the serum samples obtained from RCC patients. Five paired (RCC and adjacent normal) and 2 pooled sets of samples were utilized. Out of the 3,167 identified proteins from MS spectra 78 of interest (p value ≤ 0.05; 0.9 % protein decoy FDR; 0.07 % peptide decoy FDR; fold change ≥ 1) were selected through scaffold analysis with up regulated expression of 42 proteins in tumor along with 36 downregulated proteins. From the panel of 13 proteins i.e. ACTG2, A2M, FETUA, CAP1, OSTF1, RL32, PDLI1, GBB1, MAP1B, RL30, PIMT, C163A, SC22B and SMD3 that were not previously reported in RCC, two proteins; alpha -2-macroglobulin (A2M) and alpha-2-HS glycoprotein (FetuA) were subjected to validation through multiplexed analysis by Luminex and immunohistochemistry. We found upregulated expression of A2M (2.6 folds) and FetuA (1.6 folds) along with decreased serum excretion (P=0.0061) (P=0.0002) in RCC patients, respectively. The expression was validated through histochemical studies of the tissue samples. Further studies on larger sample size and rich validity cohort shall elucidate the role of A2M and FetuA to serve as novel therapeutic interventions for RCC.
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