Integrative multi-omics analysis identifies ATAD1 as a potential regulator of metastasis in pancreatic cancer.

Pancreatic cancer is one of the most invasive malignant tumors and remains a leading cause of cancer-related deaths, among which pancreatic ductal adenocarcinoma (PDAC) serves as the most common type of pancreatic cancer. Metastasis development is one of the critical reasons for the high mortality in PDAC. Previous studies usually used single or two omics integrated methods to discover biological processes and biomarkers related to the tumorigenesis and prognosis of PDAC. However, the molecular mechanisms of PDAC metastasis remain largely unknown. Therefore, we intended to integrate multi-omics data to explore the metastasis of PDAC. To identify genes or pathways that have potential roles in PDAC metastasis at different levels, we performed whole-exome sequencing (WES), RNA sequencing (RNA-Seq) and LC-MS/MS-based proteomics analysis on primary-derived (BxPC-3, MIA PaCa-2) and metastasis-derived (CFPAC-1, HPAF-II, SW1990) PDAC cell lines. Through multi-omics integrative analysis, we found that ATAD1 (ATPase Family AAA Domain Containing 1) knockdown significantly suppressed migration and invasion capacities of PDAC cells. Finally, analysis of the TCGA pancreatic adenocarcinoma (TCGA-PAAD) cohort further revealed that high ATAD1 expression was associated with significantly shorter overall survival (log-rank p = 0.012) and progressively increased from well- to poorly differentiated tumors, implicating ATAD1 as a potential regulator of metastatic propensity and dedifferentiation in pancreatic cancer.