Kim Ock-Hwa, Choi Bo-Yun, Kim Dong Kwan, Kim Na Hyun, Rho Jin Kyung, Sul Woo Jun, Lee Sei Won
Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine Seoul, Republic of Korea.
Division of Allergy and Pulmonology, Department of Internal Medicine, Chungnam National University Sejong Hospital Sejong, Republic of Korea.
Am J Cancer Res. 2022 May 15;12(5):2350-2362. eCollection 2022.
Lung cancer is the primary cause of cancer-related deaths worldwide. Recently, although the microbiome has emerged as the key modulator of the carcinogenesis, it has not been evaluated in lung cancer. Here, we evaluated the microbial composition of lung cancer tissues according to the histologic type and genetic mutation, compared it with that of the adjacent normal lung tissues, and investigated the association between the lung microbiome and clinical parameters. We collected lung tissue samples from 162 patients with non-small cell lung cancer (NSCLC, 162 cancer and 54 adjacent normal tissues), surgically resected between January 2018 and December 2019, and analyzed their microbiome using 16S rRNA gene amplicon sequencing, the QIIME2 pipeline, and statistical analyses. NSCLC tissues had significantly lower alpha diversity than the normal tissues, and their microbial composition differed according to the histologic type and cancer genetic mutation. The genera , and were significantly overrepresented in NSCLC tissues. Alpha diversity steadily declined from a normal to a more advanced stage, and microbial compositional differences were noted along with recurrence. was the most predominant genus in the NSCLC tissues of patients with recurrence. The pathways related to the tricarboxylic acid cycle and L-glutamate and L-glutamine biosynthesis were predominant in adenocarcinoma, whereas those related to purine and pyrimidine nucleotide degradation and formaldehyde assimilation were predominant in squamous cell carcinoma. Our findings suggest that the altered lung cancer microbial composition might be associated with cancer initiation and/or progression.
肺癌是全球癌症相关死亡的主要原因。最近，尽管微生物群已成为致癌作用的关键调节因子，但尚未在肺癌中进行评估。在此，我们根据组织学类型和基因突变评估了肺癌组织的微生物组成，将其与相邻正常肺组织的微生物组成进行比较，并研究了肺微生物群与临床参数之间的关联。我们收集了2018年1月至2019年12月期间手术切除的162例非小细胞肺癌患者（162个癌组织和54个相邻正常组织）的肺组织样本，并使用16S rRNA基因扩增子测序、QIIME2流程和统计分析对其微生物群进行了分析。非小细胞肺癌组织的α多样性显著低于正常组织，其微生物组成根据组织学类型和癌症基因突变而有所不同。在非小细胞肺癌组织中，属、和的含量显著过高。从正常阶段到更晚期阶段，α多样性稳步下降，并且随着复发出现微生物组成差异。是复发患者非小细胞肺癌组织中最主要的属。与三羧酸循环以及L-谷氨酸和L-谷氨酰胺生物合成相关的途径在腺癌中占主导地位，而与嘌呤和嘧啶核苷酸降解以及甲醛同化相关的途径在鳞状细胞癌中占主导地位。我们的研究结果表明，肺癌微生物组成的改变可能与癌症的发生和/或进展有关。
