Department of Thoracic Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Cell Infect Microbiol. 2023 Jan 20;13:1091825. doi: 10.3389/fcimb.2023.1091825. eCollection 2023.
Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and is one of the most fatal cancers worldwide. Recently, the International Association for the Study of Lung Cancer (IASLC) proposed a novel grading system based on the predominant and high-grade histological patterns for invasive pulmonary adenocarcinoma (IPA). To improve outcomes for NSCLC patients, we combined serum metabolomics and fecal microbiology to screen biomarkers in patients with early-stage NSCLC and identified characteristic microbial profiles in patients with different grades of IPA. 26 genera and 123 metabolites were significantly altered in the early-stage NSCLC patients. , , , and were more abundant in the early-stage NSCLC patients compared with healthy controls. For the different grades of IPA, the characteristic microorganisms are as follows: and in IPA grade type 1; in IPA grade type 2; and in IPA grade type 3. In the metabolome results, the early-stage NSCLC group mainly included higher levels of sphingolipids (D-erythro-sphingosine 1-phosphate, palmitoyl sphingomyelin), fatty acyl (Avocadyne 1-acetate, 12(S)-HETE, 20-Carboxy-Leukotriene B4, Thromboxane B3, 6-Keto-prostaglandin f1alpha, Sebacic acid, Tetradecanedioic acid) and glycerophospholipids (LPC 20:2, LPC 18:0, LPC 18:4, LPE 20:2, LPC 20:1, LPC 16:1, LPC 20:0, LPA 18:2, LPC 17:1, LPC 17:2, LPC 19:0). Dysregulation of pathways, such as sphingolipid metabolism and sphingolipid signaling pathway may become an emerging therapeutic strategy for early-NSCLC. Correlation analysis showed that gut microbiota and serum metabolic profiles were closely related, while and were the core genera. These findings provide new biomarkers for the diagnosis of early-stage NSCLC and the precise grading assessment of prognostic-related IPAs, which are of clinical importance and warrant further investigation of the underlying molecular mechanisms.
非小细胞肺癌（NSCLC）是肺癌的主要形式，也是全球最致命的癌症之一。最近，国际肺癌研究协会（IASLC）提出了一种基于侵袭性肺腺癌（IPA）主要和高级别组织学模式的新型分级系统。为了改善 NSCLC 患者的预后，我们结合血清代谢组学和粪便微生物组学，筛选早期 NSCLC 患者的生物标志物，并确定不同 IPA 分级患者的特征性微生物谱。在早期 NSCLC 患者中，有 26 个属和 123 种代谢物发生显著变化。与健康对照组相比，早期 NSCLC 患者中 、 、 、 和 更为丰富。对于不同等级的 IPA，特征性微生物如下：IPA 等级 1 型中为 和 ；IPA 等级 2 型中为 ；IPA 等级 3 型中为 。在代谢组学结果中，早期 NSCLC 组主要包括鞘脂（D-erythro-sphingosine 1-phosphate，palmitoyl sphingomyelin）、脂肪酸酰基（Avocadyne 1-acetate，12(S)-HETE，20-Carboxy-Leukotriene B4，Thromboxane B3，6-Keto-prostaglandin f1alpha，Sebacic acid，Tetradecanedioic acid）和甘油磷脂（LPC 20:2，LPC 18:0，LPC 18:4，LPE 20:2，LPC 20:1，LPC 16:1，LPC 20:0，LPA 18:2，LPC 17:1，LPC 17:2，LPC 19:0）水平升高。鞘脂代谢和鞘脂信号通路等途径的失调可能成为早期 NSCLC 的一种新兴治疗策略。相关性分析表明，肠道微生物群和血清代谢谱密切相关，而 和 是核心属。这些发现为早期 NSCLC 的诊断和与预后相关 IPA 的精确分级评估提供了新的生物标志物，具有重要的临床意义，值得进一步研究其潜在的分子机制。
