Department of Chest Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
Int J Mol Sci. 2022 Jun 24;23(13):7037. doi: 10.3390/ijms23137037.
Lung cancers are life-threatening malignancies that cause great healthcare burdens in Taiwan and worldwide. The 5-year survival rate for Taiwanese patients with lung cancer is approximately 29%, an unsatisfactorily low number that remains to be improved. We first reviewed the molecular epidemiology derived from a deep proteogenomic resource in Taiwan. The nuclear factor erythroid 2-related factor 2 (NRF2)antioxidant mechanism was discovered to mediate the oncogenesis and tumor progression of lung adenocarcinoma. Additionally, DNA replication, glycolysis and stress response are positively associated with tumor stages, while cell-to-cell communication, signaling, integrin, G protein coupled receptors, ion channels and adaptive immunity are negatively associated with tumor stages. Three patient subgroups were discovered based on the clustering analysis of protein abundance in tumors. The first subgroup is associated with more advanced cancer stages and visceral pleural invasion, as well as higher mutation burdens. The second subgroup is associated with L858R mutations. The third subgroup is associated with PI3K/AKT pathways and cell cycles. Both EGFR and PI3K/AKT signaling pathways have been shown to induce NRF2 activation and tumor cell proliferation. We also reviewed the clinical evidence of patient outcomes in Taiwan given various approved targeted therapies, such as EGFR-tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK)inhibitors, in accordance with the patients' characteristics. Somatic mutations occurred in and genes, and these mutations have been detected in 55.7%, 5.2%, 2.0% and 0.7% patients, respectively. The mutation is the most prevalent targetable mutation in Taiwan. translocations have been found in 9.8% of patients with wild-type . The molecular profiling of advanced NSCLC is critical to optimal therapeutic decision-making. The patient characteristics, such as mutation profiles, protein expression profiles, drug-resistance profiles, molecular oncogenic mechanisms and patient subgroup systems together offer new strategies for personalized treatments and patient care.
肺癌是危及生命的恶性肿瘤，在台湾和全球范围内给医疗保健带来了巨大负担。台湾肺癌患者的 5 年生存率约为 29%，这个数字令人不满意，仍有待提高。我们首先回顾了从台湾深度蛋白质基因组资源中得出的分子流行病学。核因子红细胞 2 相关因子 2（NRF2）抗氧化机制被发现介导肺腺癌的发生和肿瘤进展。此外，DNA 复制、糖酵解和应激反应与肿瘤分期呈正相关，而细胞间通讯、信号、整合素、G 蛋白偶联受体、离子通道和适应性免疫与肿瘤分期呈负相关。根据肿瘤中蛋白质丰度的聚类分析，发现了三个患者亚组。第一亚组与更晚期的癌症阶段、内脏胸膜侵犯以及更高的突变负担有关。第二亚组与 L858R 突变有关。第三亚组与 PI3K/AKT 通路和细胞周期有关。EGFR 和 PI3K/AKT 信号通路都被证明可以诱导 NRF2 激活和肿瘤细胞增殖。我们还根据患者的特征，回顾了在台湾接受各种批准的靶向治疗（如 EGFR-酪氨酸激酶抑制剂和间变性淋巴瘤激酶（ALK）抑制剂）的患者的临床结局证据。和 基因发生体细胞突变，这些突变分别在 55.7%、5.2%、2.0%和 0.7%的患者中检测到。在台湾， 突变是最常见的可靶向突变。在野生型 中发现了 易位，占患者的 9.8%。晚期 NSCLC 的分子谱分析对于最佳治疗决策至关重要。患者特征，如突变谱、蛋白质表达谱、耐药谱、分子致癌机制和患者亚组系统，共同为个性化治疗和患者护理提供了新的策略。
