Integrating Genetic and Transcriptomic Data to Reveal Pathogenesis and Prognostic Markers of Pancreatic Adenocarcinoma

Abstract

Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies and mortality for PAAD have remained increasing under the conditions of substantial improvements in mortality for other major cancers. Although multiple of studies exists on PAAD, few studies have dissected the oncogenic mechanisms of PAAD based on genomic variation. In this study, we integrated somatic mutation data and gene expression profiles obtained by high-throughput sequencing to characterize the pathogenesis of PAAD. The mutation profile containing 182 samples with 25,470 somatic mutations was obtained from The Cancer Genome Atlas (TCGA). The mutation landscape was generated and somatic mutations in PAAD were found to have preference for mutation location. The combination of mutation matrix and gene expression profiles identified 31 driver genes that were closely associated with tumor cell invasion and apoptosis. Co-expression networks were constructed based on 461 genes significantly associated with driver genes and the hub gene FAM133A in the network was identified to be associated with tumor metastasis. Further, the cascade relationship of somatic mutation-Long non-coding RNA (lncRNA)-microRNA (miRNA) was constructed to reveal a new mechanism for the involvement of mutations in post-transcriptional regulation. We have also identified prognostic markers that are significantly associated with overall survival (OS) of PAAD patients and constructed a risk score model to identify patients’ survival risk. In summary, our study revealed the pathogenic mechanisms and prognostic markers of PAAD providing theoretical support for the development of precision medicine.

Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy

“…FAM133A is a type of Cancer-Testis Antigen (CTA), a class of proteins that is highly expressed in immune privilege sites such as the brain and testis ( 57 ). High expression of FAM133A in cervical cancer and pancreatic cancer has been reported to be associated with the malignant degree of tumors ( 58 , 59 ). While in glioma, FAM133A is the downstream target of miR-155.…”

PABPC1 promotes cell proliferation and metastasis in pancreatic adenocarcinoma by regulating COL12A1 expression

“…PAAD is a type of gastrointestinal malignancy lacking early screening and diagnosis and has become a global health problem 21 . The nosogeny of PAAD is a complex process triggered by the interaction of genetic and environmental factors 22,23 . Elucidating the factors linked to the occurrence and development of PAAD is necessary to further comprehend the etiology and seek novel therapeutic targets.…”

“…21 The nosogeny of PAAD is a complex process triggered by the interaction of genetic and environmental factors. 22,23 Elucidating the factors linked F I G U R E 4 Cytoplasmic poly (A) binding protein-1 (PABPC1) regulates the expression of correlated genes in BXPC3 cells. After transfection with PABPC1 silenced vectors (siPABPC1) (#1, #2 and #3) and negative controls (siCrtl) (#1, #2 and #3) vectors in BXPC3 cells for 48 h, the differential gene expression levels of (A) zinc-α2-glycoprotein (AZGP1), (B) Rho GTPase activating protein 30 (ARHGAP30), (C) Caveolin-1 (CAV1), and (D) collagen type XII α1 chain (COL12A1) were examined with the aid of reverse transcription-quantitative polymerase chain reaction assay.…”

“… 21 The nosogeny of PAAD is a complex process triggered by the interaction of genetic and environmental factors. 22 , 23 Elucidating the factors linked to the occurrence and development of PAAD is necessary to further comprehend the etiology and seek novel therapeutic targets. Herein, our research showed that PABPC1 was expressed at high levels in patients with PAAD, which was associated with poor prognosis.…”