Wu Licheng, Kang Poming, Tao Shaolin, Zhao Zhikun, Chen Longyun, Xiao Yajie, Tan Qunyou
Department of Thoracic Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, China.
YuceBio Technology Co., Ltd., Shenzhen, 518000, China.
BMC Med Genomics. 2020 Jan 31;13(1):15. doi: 10.1186/s12920-020-0663-8.
Multifocal lung cancers (MLCs) are common in patients newly diagnosed with lung cancer, and histological results of most synchronous MLCs are similar. Few cases with different histology findings have been reported, and no genomic or transcriptomic profiling of this kind of cases were done before. Here, we analyzed genomic and transcriptomic profiles of all lung tumors from 2 patients with synchronous adenocarcinoma and squamous cell carcinoma in the same lung lobe.
Two patients were diagnosed as synchronous adenocarcinoma and squamous cell carcinoma and underwent surgical resection. All 4 tumors showed distinct genomic profiles, therefore were independent primary tumors. Several cancer-associated pathways, such as RTK-RAS pathway and Notch pathway, exhibited different mutated genes in different tumors from the same patient. Several known cancer genes with different mutations, including TP53 and KEAP1, were also detected. Mutation signature analysis demonstrated that the tumor initiation might be related to the transcription coupled nucleotide excision repair process. Two tumors for these 2 patients had loss of heterogeneity (LOH) in HLA genes, showing tumor escaping mechanism. Furthermore, tumor microenvironments showed different patterns in 2 tumors from the same patient. The tumor with more neoantigens and no HLA LOH showed more infiltrating CD8+ T cells and more clonal TCRs, indicating a more active microenvironment.
The lung squamous cell carcinoma and lung adenocarcinoma form the same patient are from independent origins. The genetic profiles and transcriptomic microenvironments are quite different for these 2 tumors. With the same genetic background, the 2 tumors in one patient exhibited different tumor escape mechanisms and immune responses, including HLA LOH and T cell infiltrating and expansion.
多灶性肺癌（MLCs）在新诊断的肺癌患者中很常见，大多数同步性MLCs的组织学结果相似。很少有不同组织学结果的病例报道，且此前未对这类病例进行过基因组或转录组分析。在此，我们分析了2例同一肺叶内同步发生腺癌和鳞状细胞癌患者的所有肺肿瘤的基因组和转录组图谱。
2例患者被诊断为同步性腺癌和鳞状细胞癌并接受了手术切除。所有4个肿瘤均显示出不同的基因组图谱，因此是独立的原发性肿瘤。几个与癌症相关的通路，如RTK-RAS通路和Notch通路，在同一患者的不同肿瘤中表现出不同的突变基因。还检测到几个具有不同突变的已知癌症基因，包括TP53和KEAP1。突变特征分析表明肿瘤起始可能与转录偶联核苷酸切除修复过程有关。这2例患者的2个肿瘤在HLA基因中存在异质性缺失（LOH），显示出肿瘤逃逸机制。此外，同一患者的2个肿瘤的肿瘤微环境呈现出不同模式。具有更多新抗原且无HLA LOH的肿瘤显示出更多浸润的CD8 + T细胞和更多克隆性TCR，表明其微环境更活跃。
同一患者的肺鳞状细胞癌和肺腺癌起源独立。这2种肿瘤的基因图谱和转录组微环境差异很大。在相同的遗传背景下，同一患者的2个肿瘤表现出不同的肿瘤逃逸机制和免疫反应，包括HLA LOH以及T细胞浸润和扩增。
