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Isolation of Proximal Fluids to Investigate the Tumor Microenvironment of Pancreatic Adenocarcinoma
Published on: November 5, 2020
Integrative analysis of gene expression profiles reveals specific signaling pathways associated with pancreatic duct
Jun Li1, Wenle Tan1, Linna Peng1
1Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P.R. China.
Background:
Pancreatic duct adenocarcinoma (PDAC) remains a major health problem because conventional cancer treatments are relatively ineffective against it. Microarray studies have linked many genes to pancreatic cancer, but the available data have not been extensively mined for potential insights into PDAC. This study attempted to identify PDAC-associated genes and signaling pathways based on six microarray-based profiles of gene expression in pancreatic cancer deposited in the gene expression omnibus database.
Methods:
Pathway network methods were used to analyze core pathways in six publicly available pancreatic cancer gene (GSE71989, GSE15471, GSE16515, GSE32676, GSE41368 and GSE28735) expression profiles. Genes potentially linked to PDAC were assessed for potential impact on survival time based on data in The Cancer Genome Atlas and International Cancer Genome Consortium databases, and the expression of one candidate gene (CKS2) and its association with survival was examined in 102 patients with PDAC from our hospital. Effects of CKS2 knockdown were explored in the PDAC cell lines BxPC-3 and CFPAC-1.
Results:
The KEGG signaling pathway called "pathway in cancer" may play an important role in pancreatic cancer development and progression. Five genes (BIRC5, CKS2, ITGA3, ITGA6 and RALA) in this pathway were significantly associated with survival time in patients with PDAC. CKS2 was overexpressed in PDAC samples from our hospital, and higher CKS2 expression in these patients was associated with shorter survival time. CKS2 knockdown substantially inhibited PDAC cell proliferation in vitro.
Conclusions:
Analysis integrating existing microarray datasets allowed identification of the "pathway in cancer" as an important signaling pathway in PDAC. This integrative approach may be powerful for identifying genes and pathways involved in cancer.
Insights
This study identified the "pathway in cancer" as crucial for pancreatic duct adenocarcinoma (PDAC). Overexpression of the gene CKS2 is linked to poorer survival in PDAC patients, and its inhibition reduces cancer cell growth.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Pancreatic duct adenocarcinoma (PDAC) presents a significant challenge due to limited treatment efficacy.
- Existing microarray data for pancreatic cancer requires further in-depth analysis to uncover potential therapeutic targets.
- This research focuses on identifying novel genes and pathways associated with PDAC using public gene expression datasets.
Purpose of the Study:
- To identify genes and signaling pathways implicated in pancreatic duct adenocarcinoma (PDAC) development and progression.
- To analyze publicly available gene expression profiles for novel insights into PDAC.
- To evaluate the prognostic significance of identified genes and their potential as therapeutic targets.
Main Methods:
- Utilized pathway network analysis on six public gene expression profiles of pancreatic cancer.
- Assessed potential PDAC-associated genes for impact on survival using The Cancer Genome Atlas and International Cancer Genome Consortium data.
- Examined CKS2 expression and its correlation with survival in 102 PDAC patients and investigated CKS2 knockdown effects in PDAC cell lines.
Main Results:
- The KEGG "pathway in cancer" was identified as a key pathway in PDAC.
- Five genes (BIRC5, CKS2, ITGA3, ITGA6, RALA) within this pathway significantly correlated with PDAC patient survival.
- Elevated CKS2 expression in PDAC patients was associated with reduced survival, and its knockdown inhibited cancer cell proliferation.
Conclusions:
- Integrative analysis of microarray datasets highlights the "pathway in cancer" as critical in PDAC.
- This bioinformatics approach is effective for discovering cancer-related genes and pathways.
- CKS2 emerges as a potential prognostic biomarker and therapeutic target for pancreatic duct adenocarcinoma.
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