ArticleInternational journal of cancer2019
Alternative splicing expands the prognostic impact of KRAS in microsatellite stable primary colorectal cancer.
Article in International journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Alternative Splicing in Tumorigenesis and Cancer Therapy.Biomolecules · 2025Review
- Transcripts of splicing factors with time-varying associations with survival outcomes in colorectal cancer.American journal of cancer research · 2025Article
- Mapping alternative splicing events in colorectal cancer.Discover oncology · 2024Article
- KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab.Scientific reports · 2023Article
- The role of alternative pre-mRNA splicing in cancer progression.Cancer cell international · 2023Review
- The role of alternative splicing in lung cancer.Cancer chemotherapy and pharmacology · 2023Review
- Differential functions of the KRAS splice variants.Biochemical Society transactions · 2023Review
- Alternative RNA splicing defects in pediatric cancers: new insights in tumorigenesis and potential therapeutic vulnerabilities.Annals of oncology : official journal of the European Society for Medical Oncology · 2022Review
- Identification of the prognostic signature based on genomic instability-related alternative splicing in colorectal cancer and its regulatory network.Frontiers in bioengineering and biotechnology · 2022Article
- The role of KRAS splice variants in cancer biology.Frontiers in cell and developmental biology · 2022Review
- Alternative splicing of mRNA in colorectal cancer: new strategies for tumor diagnosis and treatment.Cell death & disease · 2021Review
- Development of alternative splicing signature in lung squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2021Article
- Article
- Splice variants of RAS-translational significance.Cancer metastasis reviews · 2020Review
- Identification of novel alternative splicing isoform biomarkers and their association with overall survival in colorectal cancer.BMC gastroenterology · 2020Article
- Genomic basis for RNA alterations in cancer.Nature · 2020Article
- Pan-cancer analysis of clinical relevance of alternative splicing events in 31 human cancers.Oncogene · 2019Article
- Review
- Genome-Wide Profiling of Prognostic Alternative Splicing Signature in Colorectal Cancer.Frontiers in oncology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS mutation is a well-known marker for poor response to targeted treatment and patient prognosis in microsatellite stable (MSS) colorectal cancer (CRC). However, variation in clinical outcomes among patients wild-type for KRAS underlines that this is not a homogeneous population. Here, we evaluated the prognostic impact of KRAS alternative splicing in relation to mutation status in a single-hospital series of primary MSS CRCs (N = 258). Using splicing-sensitive microarrays and RNA sequencing, the relative expression of KRAS-4A versus KRAS-4B transcript variants was confirmed to be down-regulated in CRC compared to normal colonic mucosa (N = 41; p ≤ 0.001). This was independent of mutation status, however, gene set enrichment analysis revealed that the effect of splicing on KRAS signaling was specific to the KRAS wild-type subgroup, in which low relative KRAS-4A expression was associated with a higher level of KRAS signaling (p = 0.005). In concordance, the prognostic value of KRAS splicing was also dependent on mutation status, and for patients with Stage I-III KRAS wild-type MSS CRC, low relative KRAS-4A expression was associated with inferior overall survival (HR: 2.36, 95% CI: 1.07-5.18, p = 0.033), a result not found in mutant cases (p
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