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Exploring the importance of cancer pathways by meta-analysis of differential protein expression networks in three
Sinjini Sikdar1, Somnath Datta1, Susmita Datta2
1Department of Biostatistics, University of Florida, Gainesville, FL, 32611, USA.
Background:
It is believed that all cancers occur due to the mutation or change in one or more genes. In order to investigate the significance of the biological pathways which are interrupted by these genetic mutations, we pursue an integrated analysis using multiple cancer datasets released by the International Cancer Genome Consortium (ICGC). This dataset consists of expression profiles for genes/proteins of patients receiving treatment, for three types of cancer - Head and Neck Squamous Cell Carcinoma (HNSC), Lung Adenocarcinoma (LUAD) and Kidney Renal Clear Cell Carcinoma (KIRC). We consider pathway analysis to identify all the biological pathways which are active among the patients and investigate the roles of the significant pathways using a differential network analysis of the protein expression datasets for the three cancers separately. We then integrate the pathway based results of all the three cancers which provide a more comprehensive picture of the three cancers.
Results:
From our analysis of the protein expression data, overall, RAS and PI3K signaling pathways appear to play the most significant roles in the three cancers - Head and Neck Squamous Cell Carcinoma (HNSC), Lung Adenocarcinoma (LUAD) and Kidney Renal Clear Cell Carcinoma (KIRC).
Conclusion:
This analysis suggests that the RAS and PI3K signaling pathways are the two most important pathways in all the three cancers and should be investigated further for their potential roles in cancers.
Reviewers:
This article was reviewed by Joaquin Dopazo and Samiran Ghosh.
Insights
RAS and PI3K signaling pathways are crucial in Head and Neck Squamous Cell Carcinoma, Lung Adenocarcinoma, and Kidney Renal Clear Cell Carcinoma. Further research into these key cancer pathways is recommended.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Cancer development is linked to genetic mutations affecting biological pathways.
- The International Cancer Genome Consortium (ICGC) provides valuable multi-cancer datasets.
- Understanding disrupted pathways is key to cancer research.
Purpose of the Study:
- To investigate biological pathways altered by genetic mutations across three distinct cancer types.
- To identify and analyze the roles of significant pathways in Head and Neck Squamous Cell Carcinoma (HNSC), Lung Adenocarcinoma (LUAD), and Kidney Renal Clear Cell Carcinoma (KIRC).
- To integrate findings across cancers for a comprehensive understanding.
Main Methods:
- Utilized integrated analysis of multi-cancer datasets from ICGC.
- Performed pathway analysis on gene/protein expression profiles.
- Conducted differential network analysis on protein expression data for each cancer type separately.
- Integrated pathway-based results from all three cancers.
Main Results:
- RAS and PI3K signaling pathways were identified as highly significant across all three studied cancers.
- These pathways showed prominent roles in the molecular landscape of HNSC, LUAD, and KIRC.
- Protein expression data analysis highlighted the importance of these signaling cascades.
Conclusions:
- RAS and PI3K signaling pathways are critically important in HNSC, LUAD, and KIRC.
- These pathways warrant further investigation for their potential therapeutic implications in cancer treatment.
- The study underscores the value of integrated pathway analysis in oncology research.
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