SynthesisCancer medicine2024
Mismatch repair protein deficiency and its implications on distant metastasis in colorectal cancer: A comprehensive analysis.
Synthesis in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.
- Mismatch repair protein deficiency and its implications on distant metastasis in colorectal cancer: A comprehensive analysis.Cancer medicine · 2024Pooled it
- Comprehensive Overview of Gastric Cancer Immunohistochemistry: Key Biomarkers, Advanced Detection Methods, and Perspectives.Medicina (Kaunas, Lithuania) · 2026Review
- DNA mismatch repair (MMR) genes expression in lung cancer and its correlation with different clinicopathologic parameters.Scientific reports · 2025Article
- Screening for Cervical Intraepithelial Lesions with TCT and HPV DNA: A Triage Strategy.International journal of women's health · 2025Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWhile previous studies have indicated variability in distant metastatic potential among different mismatch repair (MMR) states in colorectal cancer (CRC), their findings remain inconclusive, especially considering potential differences across various ethnic backgrounds. Furthermore, the gene regulatory networks and the underlying mechanisms responsible for these variances in metastatic potential across MMR states have yet to be elucidated.
methodsWe collected 2058 consecutive primary CRC samples from the South West of China and assessed the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) using immunohistochemistry. To explore the inconsistencies between different MMR statuses and recurrence, we performed a meta-analysis. To delve deeper, we employed Weighted Gene Co-expression Network Analysis (WGCNA), ClueGo, and iRegulon, pinpointing gene expression networks and key regulatory molecules linked to metastasis and recurrence in CRC. Lastly, both univariate and multivariate Cox regression analyses were applied to determine the impact of core regulatory molecules on metastasis.
resultsOf the samples, 8.2% displayed deficient MMR (dMMR), with losses of MLH1 and PSM2 observed in 40.8% and 63.9%, respectively. A unique 24.3% isolated loss of PMS2 without concurrent metastasis was identified, a result that diverges from established literature. Additionally, our meta-analysis further solidifies the reduced recurrence likelihood in dMMR CRC samples compared to proficient MMR (pMMR). Two gene expression networks tied to distant metastasis and recurrence were identified, with a majority of metastasis-related genes located on chromosomes 8 and 18. An IRF1 positive feedback loop was discerned in the metastasis-related network, and IRF1 was identified as a predictive marker for both recurrence-free and distant metastasis-free survival across multiple datasets.
conclusionGeographical and ethnic factors might influence peculiarities in MMR protein loss. Our findings also highlight new gene expression networks and crucial regulatory molecules in CRC metastasis, enhancing our comprehension of the mechanisms driving distant metastasis.
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