Lung adenocarcinoma (LUAD) is a prevalent form of non-small cell lung cancer with a rising incidence in recent years. Understanding the mutation characteristics of LUAD is crucial for effective treatment and prediction of this disease. Among the various mutations observed in LUAD, KRAS mutations are particularly common. Different subtypes of KRAS mutations can activate the Ras signaling pathway to varying degrees, potentially influencing the pathogenesis and prognosis of LUAD. This study aims to investigate the relationship between different KRAS mutation subtypes and the pathogenesis and prognosis of LUAD. A total of 63 clinical samples of LUAD were collected for this study. The samples were analyzed using targeted gene sequencing panels to obtain sequencing data. To complement the dataset, additional clinical and sequencing data were obtained from TCGA and MSK. The analysis revealed significantly higher Ki67 immunohistochemical scores in patients with missense mutations compared to controls. Moreover, the expression level of KRAS was found to be significantly correlated with Ki67 expression. Enrichment analysis indicated that KRAS missense mutations activated the SWEET_LUNG_CANCER_KRAS_DN and CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2 pathways. Additionally, patients with KRAS missense mutations and high Ki67 IHC scores exhibited significantly higher tumor mutational burden levels compared to other groups, which suggests they are more likely to be responsive to ICIs. Based on the data from MSK and TCGA, it was observed that patients with KRAS missense mutations had shorter survival compared to controls, and Ki67 expression level could more accurately predict patient prognosis. In conclusion, when utilizing KRAS mutations as biomarkers for the treatment and prediction of LUAD, it is important to consider the specific KRAS mutant subtypes and Ki67 expression levels. These findings contribute to a better understanding of LUAD and have implications for personalized therapeutic approaches in the management of this disease.

肺腺癌（LUAD）是非小细胞肺癌的一种常见形式，近年来发病率不断上升。了解 LUAD 的突变特征对于有效治疗和预测该疾病至关重要。在 LUAD 中观察到的各种突变中，KRAS 突变尤其常见。 KRAS突变的不同亚型可以不同程度地激活Ras信号通路，可能影响LUAD的发病机制和预后。本研究旨在探讨不同KRAS突变亚型与LUAD发病机制及预后的关系。本研究共收集了 63 份 LUAD 临床样本。使用靶向基因测序面板对样品进行分析以获得测序数据。为了补充数据集，从 TCGA 和 MSK 获得了额外的临床和测序数据。分析显示，与对照组相比，错义突变患者的 Ki67 免疫组织化学评分显着更高。此外，发现KRAS的表达水平与Ki67的表达显着相关。富集分析表明，KRAS 错义突变激活了 SWEET_LUNG_CANCER_KRAS_DN 和 CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2 通路。此外，与其他组相比，具有 KRAS 错义突变和高 Ki67 IHC 评分的患者表现出显着更高的肿瘤突变负荷水平，这表明他们更有可能对 ICI 产生反应。基于MSK和TCGA的数据，观察到KRAS错义突变的患者与对照相比生存期更短，Ki67表达水平可以更准确地预测患者预后。 总之，当利用 KRAS 突变作为 LUAD 治疗和预测的生物标志物时，考虑特定的 KRAS 突变亚型和 Ki67 表达水平非常重要。这些发现有助于更好地理解 LUAD，并对治疗该疾病的个性化治疗方法具有影响。