ArticleCancer medicine2026
Distinct Molecular and Prognostic Profiles of Left- and Right-Sided Colorectal Cancer Revealed by NGS Analysis: The Role of SMAD4 and SETD2 Mutations.
Article in Cancer medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- PRDM Proteins Orchestrate Colorectal Cancer Tumorigenesis.International journal of molecular sciences · 2026Review
- Distinct Molecular and Prognostic Profiles of Left- and Right-Sided Colorectal Cancer Revealed by NGS Analysis: The Role of SMAD4 and SETD2 Mutations.Cancer medicine · 2026Article
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10 authors.
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Abstract
backgroundColorectal cancer (CRC) isthe third most common cancer and the second leading cause of cancer-relateddeath worldwide. Its genetic heterogeneity complicates treatment. This studyaimed to compare clinicopathological, molecular, and prognostic factors betweenleft-sided (LCC) and right-sided (RCC) CRC.
methodsWe retrospectively analyzed 48 CRCpatients who received next-generation sequencing (NGS) of tumor tissue andmatched leukocytes using a 425-gene panel. Clinicopathological, molecular, andprognostic factors were compared between LCC and RCC.
resultsRCC exhibited a higher frequencyof BRAF mutations (33.3% vs. 7.1%, p = 0.042) and more frequent alterations in PI3K (p = 0.033), homology-dependent recombination (HDR, p = 0.018), and mismatch repair (MMR, p = 0.002) pathways than LCC. Multivariate analysis identified SMAD4 mutation as an independentpredictor of worse overall survival (OS) (HR = 3.88, 95% CI 1.05-14.29, p = 0.042), which was confirmed in an external cohort of 1796 CRCpatients. In subgroup analyses, SETD2 mutationswere associated with poor prognosis in LCC (HR = 2.20, 95% CI 0.80-6.06, p = 0.026), while ARID1A (p = 0.040) and PRDM1 (p = 0.021) mutations correlated with shorter progression-free survival in RCC. Patients harboring both SMAD4 and SETD2 mutationshad the shortest OS (median: 17.7 months, p < 0.0001).
conclusionsThese findings reveal criticalmolecular and prognostic differences between LCC and RCC and highlight SMAD4 and SETD2 asimportant prognostic biomarkers, suggesting the potential value of location-and mutation-guided precision therapies in CRC.
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