Abstract:
Brain tumors are amongst the leading source of cancer-related morbidity and
mortality worldwide. However, the diagnostic techniques used for this are time
consuming and costly. The aim of this study was to identify the potential genetic
markers for brain cancer in the Pakistani population for diagnostic and prognostic
purposes through the evaluation of serum samples using GC-MS.
A total of six samples (three patients and three controls) were collected for GC-MS
analysis. The compounds that were identified were analyzed using scaffold software
and based on t-test and foldchange calculation, 25 proteins were sorted. Afterwards,
their location was determined and their metabolic pathways were mapped. PPP1R163
gene was selected for further processing based on its various roles in cancer processes
and SNP data was retrieved and filtered that was then subjected to the processing that
followed. Evolutionary conservation, structure analysis, stability analysis and
investigation into its link with cancer was carried out.
Most proteins were localized in the cytoplasm while some were in the nucleus,
mitochondria and endoplasmic reticulum. RAB5C and ACADV were anti-apoptotic
leading to enhanced proliferation while RPL7 lead to cancer angiogenesis and
metastasis. Additionally, SSRP1 was both pro-proliferative and tumor suppressive
that indirectly activated PPP1R163 gene. Among the 7 deleterious variants of this
gene, 4 of them; L387P, R274C, K246M and E92A had a significant impact on
protein function while destabilization was caused by most of the SNPs. S405F was
the most associated with cancer.
Due to limitations and lack of existing data on cancer in Pakistan, it is difficult to
study cancer and its effects on the population. This study identifies the different
prognostic genetic markers for brain cancer and brings focus on PPP1R163 as an
important gene with its link to brain cancer and as a potential future therapeutic target.
