Climent Carla, Soriano Sandra, Lopez Natalia, Giner Julia, Blazquez Mari Carmen, Carrera Ruben, Sierra Marina, Cobo Pablo, Fragio Monica, Busquets Mireia, Cano Ona Cano I, Carrasco Alicia, Seguí Miguel Ángel, Vila Laia
Department of Medical Oncology, Consorcio Hospital Universitario Parc Tauli, Sabadell 08208, Spain.
Department of Pathological Anatomy, Consorcio Hospital Universitario Parc Tauli, Sabadell 08208, Spain.
Ecancermedicalscience. 2025 May 27;19:1914. doi: 10.3332/ecancer.2025.1914. eCollection 2025.
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.
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.
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 ( = 0.004). While differences in median overall survival were observed across KRASm subtypes, they were not statistically significant ( = 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 ( = 0.4 and = 0.06, respectively).
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.
在大约25%的非小细胞肺癌（NSCLC）腺癌患者中可检测到 Kirsten 大鼠肉瘤病毒（KRAS）突变（KRASms）。下一代测序（NGS）已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。本研究旨在调查NSCLC各阶段KRASm患者的临床和病理特征。
我们使用Illumina Focus 52基因靶向NGS检测板分析了2019年至2021年的NSCLC患者，该检测板可检测DNA和RNA改变。使用SP263抗体评估PD-L1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。
在123例患者中，62例（50.4%）有KRASm，中位年龄为67岁（范围49 - 92岁）。其中，79%为男性，87.1%为腺癌，仅8.1%为非吸烟者。仅NGS就足以对19.4%的病例进行分子特征分析；在75.8%的病例中，还需要额外进行一项单分子检测。KRASm亚型分布如下：G12C（33.8%）、G12V（25.8%）、G12D（21%）和Q61H（6.5%）。G12V在非吸烟者中更常见（60%）。24.2%的患者检测到共突变，其中PIK3CA最常见。19.4%的患者观察到PD-L1表达>50%。未发现KRAS亚型与PD-L1表达水平或共突变之间存在显著关联。不同KRASm亚型的临床分期存在显著差异。早期疾病占KRASm病例的24.19%，其中40%的患者为G12D。然而，G12C和G12V亚型更常与转移性疾病相关（P = 0.004）。虽然不同KRASm亚型的中位总生存期存在差异，但无统计学意义（P = 0.5）。共突变的存在和高PD-L1表达提示预后较差，但未达到统计学意义（分别为P = 0.4和P = 0.06）。
本研究强调了评估NSCLC中KRAS状态和亚型的重要性，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后续监测相关，在高风险患者中监测可能需要更密切。此外，虽然PD-L1状态在KRASm患者中显示出作为预后因素的潜力，但需要进一步研究来证实这种关系。
