Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea.
Oral Oncology Clinic, Research Institute and Hospital, National Cancer Center, 323 Ilsandong-gu, Goyang-si 10408, Gyeonggi-do, Republic of Korea.
Int J Mol Sci. 2024 Oct 10;25(20):10890. doi: 10.3390/ijms252010890.
The oral microbiome is crucial for human health. Although oral dysbiosis may contribute to oral cancer (OC), the detailed relationships between the microbiome and OC remain unclear. In this case-control study, we aimed to elucidate the connection between the oral microbiome and mechanisms potentially involved in oral cancer. The study analyzed 1022 oral saliva samples, including 157 from oral cancer patients and 865 from healthy controls, using 16S ribosomal RNA (16S rRNA) sequencing and a Light Gradient Boosting Machine (LightGBM) model to identify four bacterial genera significantly associated with oral cancer. In patients with oral cancer, the relative abundance of and was higher; and showed decreased relative abundance; and levels of fatty acid oxidation enzymes, including Carnitine palmitoyltransferase 1A (CPT1A), long-chain acyl-CoA synthetase, acyl-CoA dehydrogenase, diacylglycerol choline phosphotransferase, and H+-transporting ATPase, were significantly higher compared to controls. Conversely, healthy controls exhibited increased levels of short-chain fatty acids (SCFAs) and CD4+T-helper cell counts. Survival analysis revealed that higher abundance of and , which correlated positively with interleukin-6, tumor necrosis factor-alpha, and CPT1A, were linked to poorer disease-free survival (DFS) and overall survival (OS) rates, while and were associated with better outcomes. These findings suggest that changes in these bacterial genera are associated with alterations in specific cytokines, CPT1A levels, SCFAs in oral cancer, with lower SCFA levels in patients reinforcing this link. Overall, these microbiome changes, along with cytokine and enzyme alterations, may serve as predictive markers, enhancing diagnostic accuracy for oral cancer.
口腔微生物组对人类健康至关重要。尽管口腔微生态失调可能导致口腔癌（OC），但微生物组与 OC 之间的详细关系仍不清楚。在这项病例对照研究中，我们旨在阐明口腔微生物组与口腔癌潜在机制之间的联系。该研究分析了 1022 份口腔唾液样本，包括 157 份来自口腔癌患者和 865 份来自健康对照者，使用 16S 核糖体 RNA（16S rRNA）测序和 Light Gradient Boosting Machine（LightGBM）模型来识别与口腔癌显著相关的四个细菌属。在口腔癌患者中，和的相对丰度较高；和的相对丰度较低；以及脂肪酸氧化酶的水平，包括肉碱棕榈酰转移酶 1A（CPT1A）、长链酰基辅酶 A 合成酶、酰基辅酶 A 脱氢酶、二酰基甘油胆碱磷酸转移酶和 H+-转运 ATP 酶，与对照组相比显著升高。相反，健康对照组表现出短链脂肪酸（SCFA）和 CD4+T 辅助细胞计数的增加。生存分析显示，与白细胞介素-6、肿瘤坏死因子-α和 CPT1A 呈正相关的和的丰度增加与无病生存率（DFS）和总生存率（OS）的降低有关，而和与更好的预后相关。这些发现表明，这些细菌属的变化与特定细胞因子、CPT1A 水平、口腔癌中 SCFA 的变化以及患者中 SCFA 水平的降低有关，这进一步证实了这一联系。总的来说，这些微生物组的变化，以及细胞因子和酶的改变，可能作为预测标志物，提高口腔癌的诊断准确性。
