Identifying conserved metastatic pathways across cancers through integrated transcriptomic and network analysis.

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Metastasis is the primary cause of cancer mortality.
• Understanding shared molecular mechanisms across diverse cancer types is crucial for developing effective therapies.
• Conserved metastatic pathways represent promising therapeutic targets.

Purpose of the Study:

• To identify conserved molecular pathways and genes involved in cancer metastasis.
• To investigate the prognostic significance of these conserved elements across multiple cancer types.
• To provide a framework for understanding and targeting common metastatic processes.

Main Methods:

• Integrative analysis of RNA-Seq datasets from public databases (GEO) for five cancer types.
• Identification of differentially expressed genes (DEGs) between primary and metastatic tumors using limma.
• Pathway enrichment and protein-protein interaction (PPI) network analysis to identify hub genes.
• Validation of key pathways and hub genes using TCGA datasets and Cox regression models across 15 cancer types.

Main Results:

• Identified 10 overlapping DEGs across breast, lung, endometrial, prostate, and colorectal cancers.
• ITGAX and CXCL12 emerged as key hub genes.
• Connected hub genes to critical pathways including ERBB4 signaling, integrin-mediated adhesion, glycosphingolipid metabolism, and platelet function.
• Validated prognostic significance of ITGAX (in 6/15) and CXCL12 (in 2/15) across multiple cancer types.

Conclusions:

• Identified conserved genes and pathways critical for metastasis across diverse cancer types.
• ERBB4 signaling, ITGAX, and CXCL12 are highlighted as key regulators of the metastatic process.
• Findings provide a foundation for developing targeted therapies against common metastatic mechanisms.