Clinical and prognostic characteristics of metastatic colorectal cancer with minor <em>RAS</em> mutations

Kojitani,Yoshiki; Sakai,Daisuke; Ogata,Takatsugu; Amano,Yumi; Mori,Ryota; Kitakaze,Masatoshi; Sueda,Toshinori; Otsuka,Tomoyuki; Nishio,Minako; Ishihara,Mikiya; Kagawa,Yoshinori; Nishimura,Junichi; Sugimoto,Naotoshi; Yagi,Toshinari; Takeda,Masayuki; Yasui,Masayoshi; Kudo,Toshihiro

doi:10.3892/ol.2025.15123

Clinical and prognostic characteristics of metastatic colorectal cancer with minor RAS mutations

Authors:
- Yoshiki Kojitani
- Daisuke Sakai
- Takatsugu Ogata
- Yumi Amano
- Ryota Mori
- Masatoshi Kitakaze
- Toshinori Sueda
- Tomoyuki Otsuka
- Minako Nishio
- Mikiya Ishihara
- Yoshinori Kagawa
- Junichi Nishimura
- Naotoshi Sugimoto
- Toshinari Yagi
- Masayuki Takeda
- Masayoshi Yasui
- Toshihiro Kudo
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Affiliations: Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Osaka 541‑8567, Japan, Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Osaka 541‑8567, Japan, Department of Cancer Genomics and Medical Oncology, Nara Medical University, Kashihara, Nara 634‑8521, Japan
Published online on: June 2, 2025 https://doi.org/10.3892/ol.2025.15123
Article Number: 377
Copyright: © Kojitani et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Metastatic colorectal cancer (mCRC) presents notable therapeutic challenges. Rat sarcoma virus (RAS) mutations, including those in KRAS exon 2, are critical for treatment decisions; however, the role of minor RAS mutations (KRAS exons 3 and 4, and NRAS) remains underexplored. Because these mutations are increasingly identified in routine practice due to advances in RAS mutation testing that now routinely includes KRAS exons 3 and 4, and NRAS, clarifying their clinical relevance has become important for ensuring appropriate treatment selection. The present study aimed to compare the clinical and prognostic characteristics of patients with mCRC with minor RAS mutations to those with KRAS exon 2 mutations. To this end, data were retrospectively collected from patients with mCRC and RAS mutations between August 2018 and December 2023. Patients were grouped based on RAS mutation subtype: KRAS exon 2 or minor RAS mutations. RAS mutation testing was performed using the MEBGEN RASKET™‑B kit. Clinical characteristics, tumor location, metastatic patterns and survival outcomes were analyzed. Overall survival (OS) and progression‑free survival (PFS) were assessed using Kaplan‑Meier survival analysis, log‑rank tests and Cox proportional hazards regression models. Of 202 patients with RAS mutations, 170 had KRAS exon 2 mutations, whereas 32 exhibited minor RAS mutations (20 with non‑exon 2 KRAS mutations and 12 with NRAS mutations). Minor RAS mutations were more common in left‑sided CRC. No significant differences in background were observed between the two groups. Log‑rank OS was comparable for patients with KRAS exon 2 and minor RAS mutations. OS and PFS with first‑line bevacizumab‑containing therapy were also similar between the two groups. In conclusion, the prognostic impact of minor RAS mutations appears to be comparable to that of KRAS exon 2 mutations, suggesting that the current treatment strategies for RAS‑mutant CRC may not require modification based on these findings.

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