Molecular characterisation of KRAS mutations in non-small cell lung cancer across all stages.

IF 1.2 Q4 ONCOLOGY
ecancermedicalscience Pub Date : 2025-05-27 eCollection Date: 2025-01-01 DOI:10.3332/ecancer.2025.1914
Carla Climent, Sandra Soriano, Natalia Lopez, Julia Giner, Mari Carmen Blazquez, Ruben Carrera, Marina Sierra, Pablo Cobo, Monica Fragio, Mireia Busquets, Ona Cano I Cano, Alicia Carrasco, Miguel Ángel Seguí, Laia Vila
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引用次数: 0

Abstract

Introduction: Kirsten rat sarcoma virus (KRAS) mutations (KRASms) are detected in approximately 25% of non-small cell lung cancer (NSCLC) patients with adenocarcinoma. Next-generation sequencing (NGS) has enabled the identification of diverse KRASm subtypes with distinct prognoses, co-mutation patterns and clinical characteristics. This study aimed to investigate the clinical and pathological characteristics of KRASm patients across all stages of NSCLC.

Methods: We analysed NSCLC patients from 2019 to 2021 using the Illumina Focus 52-gene targeted NGS panel, which detects DNA and RNA alterations. PD-L1 expression was assessed using the SP263 antibody. We examined the clinical and pathological characteristics of KRASm patients, including KRASm subtypes and co-mutations.

Results: Of the 123 patients, 62 (50.4%) had KRASm, with a median age of 67 years (range 49-92). Of these, 79% were male, 87.1% had adenocarcinomas and only 8.1% were non-smokers. NGS alone was sufficient for molecular characterisation in 19.4% of cases; in 75.8%, an additional single molecular test was required. KRASm subtypes were distributed as follows: G12C (33.8%), G12V (25.8%), G12D (21%) and Q61H (6.5%). G12V was more prevalent in non-smokers (60%). Co-mutations were detected in 24.2% of patients, with PIK3CA being the most frequent. PD-L1 expression >50% was observed in 19.4% of patients. No significant associations were identified between KRAS subtypes and PD-L1 expression levels or co-mutations.Significant differences in the clinical stage were noted across KRASm subtypes. Early-stage disease accounted for 24.19% of KRASm cases, with G12D observed in 40% of these patients. However, G12C and G12V subtypes were more frequently associated with metastatic disease (p = 0.004). While differences in median overall survival were observed across KRASm subtypes, they were not statistically significant (p = 0.5). The presence of co-mutations and high PD-L1 expression was suggested to be associated with a worse prognosis, without reaching statistical significance (p = 0.4 and p = 0.06, respectively).

Conclusion: This study underscores the importance of assessing KRAS status and subtypes in NSCLC, particularly in early-stage disease, due to their association with metastatic risk. This could have relevance in treatment strategies and subsequent monitoring, which could necessarily be closer in higher risk patients. Moreover, while PD-L1 status shows potential as a prognostic factor in KRASm patients, further research is needed to confirm this relationship.

非小细胞肺癌各阶段KRAS突变的分子特征。
克尔斯滕大鼠肉瘤病毒(KRAS)突变(KRASms)在约25%的非小细胞肺癌(NSCLC)合并腺癌患者中检测到。新一代测序(NGS)已经能够识别具有不同预后、共突变模式和临床特征的多种KRASm亚型。本研究旨在探讨KRASm患者在NSCLC各个阶段的临床和病理特征。方法:我们使用Illumina Focus 52基因靶向NGS面板分析2019年至2021年的非小细胞肺癌患者,该面板检测DNA和RNA改变。用SP263抗体检测PD-L1的表达。我们检查了KRASm患者的临床和病理特征,包括KRASm亚型和共突变。结果:123例患者中,62例(50.4%)有KRASm,中位年龄为67岁(49-92岁)。其中79%是男性,87.1%患有腺癌,只有8.1%的人不吸烟。在19.4%的病例中,仅NGS就足以进行分子表征;75.8%的患者需要进行额外的单分子检测。KRASm亚型分布为:G12C(33.8%)、G12V(25.8%)、G12D(21%)和Q61H(6.5%)。G12V在非吸烟者中更为普遍(60%)。24.2%的患者检测到共突变,其中以PIK3CA最为常见。19.4%的患者PD-L1表达率为50%。KRAS亚型与PD-L1表达水平或共突变之间未发现显著关联。不同KRASm亚型的临床分期有显著差异。KRASm病例中,早期病变占24.19%,其中40%的患者存在G12D。然而,G12C和G12V亚型更常与转移性疾病相关(p = 0.004)。虽然KRASm各亚型的中位总生存期存在差异,但差异无统计学意义(p = 0.5)。共突变和PD-L1高表达与预后较差相关,但无统计学意义(p = 0.4和p = 0.06)。结论:本研究强调了评估KRAS状态和亚型在非小细胞肺癌中的重要性,特别是在早期疾病中,因为它们与转移风险相关。这可能与治疗策略和随后的监测有关,在高风险患者中可能更密切。此外,虽然PD-L1状态可能是KRASm患者的预后因素,但需要进一步的研究来证实这种关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.80
自引率
5.60%
发文量
138
审稿时长
27 weeks
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