Preliminary Study to Obtain Insights on the Proteomic Profile of Filipino Non-Small Cell Lung Carcinoma (NSCLC)

Abstract

NSCLC remains to be the leading cause of cancer incidence and mortality in the Philippines. Early diagnosis, a better understanding of drug resistance mechanisms, and proper treatment monitoring are necessary to lower the incidence and mortality rate of NSCLC. As a proof of concept to investigate the proteomic profile of Filipino NSCLC, this study performed quantitative proteomic analysis to identify aberrant expressions in the tumor tissue relative to the adjacent normal tissue specimen of one Filipino NSCLC patient. A total of 4518 proteins were identified and from this, 1855 proteins were found to be significantly differentially expressed. Functional and pathway analyses were done to the 860 upregulated and downregulated proteins with at least four-fold expression change. The analysis revealed the possible activation of the upregulated protein MUC1, a known oncogenic driver involved in the stimulation of pathways that promote angiogenesis in NSCLC tumors and prevent apoptosis. Signal transducers and activators of transcription (STAT1 and STAT3), also found upregulated in the tumor specimen, are known to interact with MUC1, which results in the expression of proteins for cell proliferation. The analysis also suggests the stabilization of HIF, which may allow cell growth in the hypoxic tumor environment and aid in metabolic adaptation in tumor cells. The results also suggest the activation of EIF2 signaling that may lead to continuous translation of oncogenic proteins. Our data demonstrate the rich proteomic information that can be obtained from profiling of the NSCLC proteome and applications for a better understanding of NSCLC tumorigenicity. Further study should be performed on a larger cohort of Filipino NSCLC patients to provide the proteomic profile of Filipino NSCLC and extract information for biomarker and drug discovery. Data are available via ProteomeXchange with identifier PXD027710.