肺腺癌组织形态学亚型的分子异质性对治疗决策构成挑战

IF 4.8 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Neoplasia Pub Date : 2024-02-03 DOI:10.1016/j.neo.2023.100955
Tobias Kolb, Sarah Müller, Peter Möller, Thomas F.E. Barth, Ralf Marienfeld
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引用次数: 0

摘要

肺癌是导致癌症相关死亡的主要原因,其中非小细胞肺癌(NSCLC)是最常见的亚型。NSCLC的重要性体现在各种靶向治疗方案上,尤其是针对NSCLC腺癌(肺腺癌(LUAD))的靶向治疗方案,以及一系列免疫疗法方案。然而,尽管取得了这些治疗进展,但大多数患者对靶向治疗或免疫检查点抑制剂都没有表现出长期反应。治疗失败的原因之一似乎是NSCLC肿瘤的异质性。由于用于病理评估的肿瘤材料有限,大多数分析都是在小型活组织切片上进行的,因此NSCLC的异质性可能会导致给定样本的分子特征描述不充分。为了更详细地了解 NSCLC LUAD 的肿瘤异质性,特别是其不同的组织形态学生长模式,我们分析了 31 例 NSLCS LUAD 患者的分离 NSCLC 生长模式区域和相应的整个肿瘤样本,并比较了它们的突变情况和表达谱。虽然肿瘤突变负荷(TMB)或微卫星不稳定性(MSI)等复杂生物标志物在鳞状生长型、乳头状生长型、微乳头状生长型、尖状生长型和实性生长型这五种生长型之间未发现明显差异,但我们观察到了各种亚克隆突变和拷贝数变异。此外,RNASeq 分析还揭示了影响细胞过程(如凋亡、转移和增殖)的生长模式特异性表达谱。总之,我们的数据为了解 LUAD 的肿瘤异质性提供了新的视角,这些视角是克服肿瘤异质性相关耐药性所必需的。
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Molecular heterogeneity in histomorphologic subtypes of lung adeno carcinoma represents a challenge for treatment decision

Lung cancer is the leading cause in cancer related death, with non-small cell lung cancer (NSCLC) being the most frequent subtype. The importance of NSCLC is reflected by the various targeted therapy options especially for NSCLC adenocarcinomas (lung adeno carcinoma (LUAD)) as well as a set of options for immune therapies. However, despite these therapy advances, the majority of patients do not show a long-term response to either targeted therapy or immune checkpoint inhibition. One reason for treatment failure appears to be the NSCLC tumor heterogeneity. NSCLC heterogeneity might lead to an insufficient molecular characterization of a given sample due to the limited tumor material used for pathological assessment as the majority of analyses is performed on small biopsies. To get a more detailed insight into the tumor heterogeneity of NSCLC LUAD, especially in the light of its different histomorphological growth patterns, we analysed isolated NSCLC growth pattern areas and the corresponding entire tumor samples of a cohort of 31 NSLCS LUAD patients and compared their mutational landscape and their expression profiles. While significant differences of complex biomarkers, like tumor mutational burden (TMB) or microsatellite instability (MSI), were not detected between the five growth patterns -lepidic, papillary, micropapillary, acinar, and solid- we observed various subclonal mutations and copy number variants. Moreover, RNASeq analysis revealed growth pattern specific expression profiles affecting cellular processes like apoptosis, metastasis and proliferation. Taken together, our data provide novel insights into the tumor heterogeneity of LUAD required to overcome tumor heterogeneity related therapy resistance.

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来源期刊
Neoplasia
Neoplasia 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
82
审稿时长
26 days
期刊介绍: Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.
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