ArticleBMC cancer2025
TP53 c.730G > A pathogenic variant as a plausible candidate biomarker in pancreatic ductal adenocarcinoma patients from Karachi, pakistan: a retrospective cohort study.
Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPancreatic cancers is known to stand among the most aggressive cancers with low survival rate. Research indicates that investigating target biomarkers can provide scientific grounds for tailored treatments in cancers. However, biomarker expression is observed to vary among different populations. Therefore, investigating the population biomarkers is a pre-requisite to understand the disease patterns and the selection of precision therapy. The biomarker spectrum of Pakistani pancreatic ductal adenocarcinoma patients remains unmapped.
methodsWe enrolled a total of 109 patients in the study and obtained FFPE tumor samples. After confirmation of diagnosis and appropriate tumor content, DNA extraction was performed. Based on the results from a pilot investigation by our group, we selected specific regions of KRAS, TP53, BRCA1 and APC genes for the current study. Extracted DNA samples were subjected to primer specific PCR for the selected gene regions followed by Sanger sequencing.
resultsA total of 59 genetic variants were found in the four selected genes, out of which 22% were pathogenic. TP53 pathogenic mutations were most frequently detected (75.2%) with all these patients carrying one consistent mutation c.730G > A. The occurrence of genetic alteration in BRCA1 was significantly associated with occurrence of alterations in KRAS (p = 0.001), TP53 (p = 0.008) and APC (p = 0.000). Moreover, the independent occurrence of mutations in TP53 (p = 0.001) and KRAS (p = 0.001) were found to significantly associated with the overall survival of the patients.
conclusionThe detection of pathogenic mutation TP53 c.730G > A is exceptionally high in our patients. This finding shows that TP53 c. 730G > A may be a plausible biomarker in the Pakistani PDAC population. It also indicates unique characteristics of the population in this specific geographical region as compared to global data. This is the first study that investigates genetic biomarkers in a large cohort of Pakistani pancreatic ductal adenocarcinoma patients. The findings from the study can provide directions about the candidate biomarkers and targeted therapies for these patients.
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