Integrated Multiomics Validation of Key MUC Gene Expression for the Signature Biomarker in the Pakistani Cohort

Pancreatic ductal adenocarcinoma (PDAC) is the 3^rd leading cause of cancer-related mortalities and has a poor prognosis, with a 5-year survival of 8%-9%. The major challenge associated with management of PDAC is delayed diagnosis. Diagnosis at an early stage can significantly increase the survival. Therefore, we used multiomics analysis to validate a novel signature biomarker of early-stage PDAC. The signature was derived from a computational analysis and subsequently validated in the Pakistani patient cohort, including patients with well-defined early-stage (I and II) PDAC.

With the aim of validating the signature biomarker (MUC3A/MUC4/MUC13/MUC16) as a potent early diagnostic and prognostic marker, a comprehensive analysis of multiomics data of the Pakistani cohort was performed utilizing the integrated whole-exome sequencing, transcriptome analysis, and RT-qPCR.

The in vitro validation of a signature biomarker in the Pakistani cohort reveals the pathogenic effect of mutations in the key MUC genes and its profound effect on its protein functionality. Among all key MUC genes analyzed in a transcriptomic dataset, only MUC4 exhibits statistically significant differential expression. Finally, RT-qPCR results demonstrate significant overexpression of all key MUC genes in PDAC blood samples.

In conclusion, our findings suggest MUC3A/MUC4/MUC13/MUC16 as robust diagnostic and prognostic biomarkers and liquid biopsy as a noninvasive approach to be integrated into daily clinical practice. This analysis can also be extended to other malignancies.