ITGA2, LAMB3, and LAMC2 may be the potential therapeutic targets in pancreatic ductal adenocarcinoma: an integrated bioinformatics analysis

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer with an abysmal prognosis rate over the last few decades. Early diagnosis and prevention could effectively combat this malignancy. Therefore, it is crucial to discover potential biomarkers to identify asymptomatic premalignant or early malignant tumors of PDAC. Gene expression analysis is a powerful technique to identify candidate biomarkers involved in disease progression. In the present study, five independent gene expression datasets, including 321 PDAC tissues and 208 adjacent non-cancerous tissue samples, were subjected to statistical and bioinformatics analysis. A total of 20 differentially expressed genes (DEGs) were identified in PDAC tissues compared to non-cancerous tissue samples. Gene ontology and pathway enrichment analysis showed that DEGs were mainly enriched in extracellular matrix (ECM), cell adhesion, ECM–receptor interaction, and focal adhesion signaling. The protein–protein interaction network was constructed, and the hub genes were evaluated. Collagen type XII alpha 1 chain (COL12A1), fibronectin 1 (FN1), integrin subunit alpha 2 (ITGA2), laminin subunit beta 3 (LAMB3), laminin subunit gamma 2 (LAMC2), thrombospondin 2 (THBS2), and versican (VCAN) were identified as hub genes. The correlation analysis revealed that identified hub genes were significantly interconnected. Wherein COL12A1, FN1, ITGA2, LAMB3, LAMC2, and THBS2 were significantly associated with PDAC pathological stages. The Kaplan–Meier survival plots revealed that ITGA2, LAMB3, and LAMC2 expression were inversely correlated with a prolonged patient survival period. Furthermore, the Human Protein Atlas database was used to validate the expression and cellular origins of hub genes encoded proteins. The protein expression of hub genes was higher in pancreatic cancer tissue than in normal pancreatic tissue samples, wherein ITGA2, LAMB3, and LAMC2 were exclusively expressed in pancreatic cancer cells. Pancreatic cancer cell-specific expression of these three proteins may play pleiotropic roles in cancer progression. Our results collectively suggest that ITGA2, LAMB3, and LAMC2 could provide deep insights into pancreatic carcinogenesis molecular mechanisms and provide attractive therapeutic targets.

Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer

“…A previous study identified LAMC2 in a proteomic analysis of PDAC cancer tissues [ 69 ], and high circulating levels of LAMC2 have been described [ 70 ]. LAMC2 overexpression in PDAC tissues has been proposed as an indicator of poor prognosis [ 71 , 72 ]. In our study, we confirm that LAMC2 is overexpressed in PDAC tissues compared to the adjacent pancreas, and that its circulating levels are significantly higher in PDAC patients relative to healthy controls.…”

Assessment of spatial transcriptomics for oncology discovery

“…ITGA2 and LAMC2 were recently identified as putative targets for PDAC, being both overexpressed in PDAC and inversely correlated with patient survival. 93 In donor C, the chemokine receptor CXCR4 and its ligand CXCL12 are co-expressed in stromal clusters containing a mixture of fibroblasts and macrophages (clusters 2, 4, and 6) ( Figure 7 G). This receptor-ligand pair is associated with tumorigenesis in a variety of cancer types, including PDAC.…”

LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

“…LAMC2 levels have already been associated with poor prognosis in several human cancers due to its effects on cancer cell proliferation, migration and invasion. In pancreatic cancer, by performing both integrated bioinformatics analyses and proteomic assays, its potential as a new putative biomarker has emerged [ 45 ]. Of note, elevated serum levels of LAMC2 in patients with pancreatic cancer make it an attractive serum-based diagnostic marker [ 46 ].…”