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MSICKB: A Curated Knowledgebase for Exploring Molecular Heterogeneity and Biomarker Prioritization in Microsatellite

Yuxin Zhang1, Xiaoyu Li1,2, Xin Zheng1

  • 1Department of Medical Oncology, Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

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Summary

Microsatellite instability (MSI) is a key cancer marker. We created MSICKB, a database of MSI features across 31 cancer types, identifying 9 hub genes for improved biomarker discovery and cancer comparison.

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Area of Science:

  • Oncology
  • Bioinformatics
  • Genomics

Background:

  • Microsatellite instability (MSI) is a crucial molecular cancer phenotype.
  • Existing MSI data is fragmented, hindering cross-cancer analysis and biomarker prioritization.

Purpose of the Study:

  • To develop a comprehensive knowledgebase (MSICKB) for MSI-associated molecular and clinical features.
  • To enable systematic cross-cancer comparisons and guide biomarker discovery.

Main Methods:

  • Manually curated 1,382 MSI-related features from 492 publications across 31 cancer types.
  • Organized evidence into genetic alterations, clinicopathology, prognosis, and therapy.
  • Constructed a bipartite network of 99 MSI-associated genes and 13 cancer types.

Main Results:

  • Identified 9 hub genes (BRAF, CD274, KRAS, MLH1, MSH2, PTEN, RNF43, TGFBR2, TP53) with cross-cancer relevance.
  • Hub genes are enriched in mismatch repair, cancer signaling, and immune regulation pathways.
  • Hub genes showed significant mutation and expression differences in MSI-high vs. non-MSI-high tumors.

Conclusions:

  • MSICKB offers a structured framework for MSI evidence synthesis and cross-cancer comparison.
  • The identified hub genes are promising candidates for MSI biomarker development.
  • MSICKB facilitates systematic biomarker prioritization for clinical actionability.