Abstract
Addressing the significant level of variability exhibited by pancreatic cancer necessitates the adoption of a systems biology approach that integrates molecular data, biological properties of the tumors, and clinical features of the patients. In this study, a comprehensive multi-omics methodology was employed to examine a distinctive collection patient dataset containing rapid autopsy tumor and normal tissue samples as well as longitudinal imaging with a focus on pancreatic cancer. By performing a whole exome sequencing analysis on tumor and normal tissues to identify somatic gene variants and a radiomics feature analysis to tumor CT images, the genome-wide association approach established a connection between pancreatic cancer driver genes and relevant radiomics features, enabling a thorough and quantitative assessment of the heterogeneity of pancreatic tumors. The significant association between sets of genes and radiomics features revealed the involvement of genes in shaping tumor morphological heterogeneity. Some results of the association established a connection between the molecular level mechanism and their outcomes at the level of tumor structural heterogeneity. Because tumor structure and tumor structural heterogeneity are related to the patients’ overall survival, patients who had pancreatic cancer driver gene mutations with an association to a certain radiomics feature have been observed to experience worse survival rates than cases without these somatic mutations. Furthermore, the outcome of the association analysis has revealed potential gene mutations and radiomics feature candidates that warrant further investigation in future research endeavors.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This research was partially supported by the Nebraska Collaboration Initiative 19 and 20 (D.Z., C.Z., M.H, H.Y, and H.D.) and NIH 5U54GM115458-03 (D.Z., C.Z., H.Y, and H.D.).
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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
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All data collection was approved by the IRB of the University of Nebraska Medical Center (Protocols: 728-16-EP and 127-18-EP).
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Data Availability
All data produced in the present work are contained in the manuscript.