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

Microsatellite instability (MSI) is a clinically actionable molecular phenotype in cancer, but MSI-associated findings remain fragmented across tumor types, study designs, and biomarker categories, limiting systematic cross-cancer comparison and evidence-guided biomarker prioritization. To address this problem, we developed the Microsatellite Instability Cancer Knowledgebase (MSICKB), a manually curated and literature-traceable resource for MSI-associated molecular and clinical features. We collected and curated 1,382 MSI-related features from 492 publications covering 31 cancer types and organized the evidence into 4 major dimensions: genetic and molecular alterations, clinicopathological features, prognostic factors, and therapeutic response. Based on curated gene-cancer associations, we constructed a simple bipartite network to examine the cross-cancer organization of MSI-associated genes. In the primary network, 99 genes were linked to 13 cancer types through 147 unique gene-cancer edges. Gene degree was strongly right-skewed, with most genes linked to a single cancer type and a small subset showing broader cross-cancer connectivity. Using an operational cutoff of degree ≥ 3, we identified 9 hub genes: BRAF, CD274, KRAS, MLH1, MSH2, PTEN, RNF43, TGFBR2, and TP53. These hubs were enriched in canonical MSI-related pathways, including mismatch repair, cancer signaling, and immune regulation. To provide external molecular support, we further evaluated the hub genes in 3 The Cancer Genome Atlas cohorts with established MSI relevance. In pooled analyses of 336 MSI-high and 1,214 non-MSI-high tumors, all 9 hub genes showed significant differences in mutation prevalence and expression. Overall, MSICKB provides a structured framework for MSI-related evidence synthesis, cross-cancer comparison, and biomarker prioritization and is freely available at http://www.sysbio.org.cn/MSICKB/.