临床环境中通过新一代测序检测到的多发性原发性肺癌的基因组和转录组意义。

IF 3.3 3区 医学 Q2 ONCOLOGY
Meihong Yao, Hu Chen, Zui Chen, Yingying Wang, Dongliang Shi, Dan Wu, Wen Li, Jianping Huang, Guizhen Chen, Qiaoling Zheng, Zhengtao Ye, Chenxin Zheng, Yinghong Yang
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引用次数: 0

摘要

有效诊断和了解多发性原发性肺癌(MPLC)肺内转移(IM)的机制有助于临床治疗。然而,临床上实际使用的检测面板各不相同。目前对多发性肺癌和肺内转移的肿瘤微环境(TME)研究尚不充分。因此,对这两种疾病的鉴别诊断和肿瘤微环境差异进行更多调查至关重要。研究人员招募了 214 名患有多种肿瘤的非小细胞肺癌患者,并对 507 份样本进行了 DNA 测序(NGS 10)。然后,对 32 名患者的标本进行了 DNA 和 RNA 测序(master panel),比较了每位患者肿瘤之间和不同患者肿瘤之间的 TME 图谱以及差异表达基因。4 名患者根据 NGS 10 结果重新分组。主小组解决了 6 例未确定患者的分类问题。MPLC的TME表现出自然杀伤(NK)细胞、CD56dim NK细胞、内皮细胞等的高度浸润,P<0.05。相反,B 细胞、活化的 B 细胞、调节细胞、未成熟树突状细胞等(P < 0.001)在 IM 中大量浸润。NECTIN4和LILRB4 mRNA在MPLC中下调(P<0.0001)。此外,NECTIN4(P<0.05)和LILRB4与MPLC无病生存率的提高有关。总之,IM 可通过病理联合 NGS 10 次检测从 MPLC 中筛选出来,然后对无法区分的患者进行大样本 NGS 检测。MPLC的优越预后可能与免疫激活的TME以及作为潜在药物治疗靶点的NECTIN4和LILRB4的下调有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genomic and transcriptomic significance of multiple primary lung cancers detected by next-generation sequencing in clinical settings.

Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management. However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM is insufficient. Therefore, additional investigation into the differential diagnosis and discrepancies in TME between two conditions is crucial. Two hundred and fourteen non-small cell lung cancer patients with multiple tumors were enrolled and 507 samples were subjected to DNA sequencing (NGS 10). Then, DNA and RNA sequencing (master panel) were performed on the specimens from 32 patients, the TME profiles between tumors within each patient and across patients and the differentially expressed genes were compared. Four patients were regrouped with NGS 10 results. Master panel resolved the classifications of six undetermined patients. The TME in MPLC exhibited a high degree of infiltration by natural killer (NK) cells, CD56dim NK cells, endothelial cells, etc., P < 0.05. Conversely, B cells, activated B cells, regulatory cells, immature dendritic cells, etc., P < 0.001, were heavily infiltrated in the IM. NECTIN4 and LILRB4 mRNA were downregulated in the MPLC (P < 0.0001). Additionally, NECTIN4 (P < 0.05) and LILRB4 were linked to improved disease-free survival in the MPLC. In conclusion, IM is screened from MPLC by pathology joint NGS 10 detections, followed by a large NGS panel for indistinguishable patients. A superior prognosis of MPLC may be associated with an immune-activating TME and the downregulation of NECTIN4 and LILRB4 considered as potential drug therapeutic targets.

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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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