Department of Oral and Maxillofacial Surgery, Zhang Zhiyuan Academician Workstation, Hainan Western Central Hospital, Shanghai Ninth People's Hospital, Danzhou, Hainan, China.
Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
J Cancer Res Clin Oncol. 2023 Aug;149(9):6097-6113. doi: 10.1007/s00432-023-04572-x. Epub 2023 Jan 19.
Oral squamous cell carcinomas (OSCCs) are primary head and neck malignant tumours with a high incidence and mortality. However, the molecular mechanisms involved in OSCC tumorigenesis are not fully understood.
OSCC and paired para-carcinoma samples were collected and used to perform multi-omics study. Transcriptomic analysis was used to reveal significant alterations in inflammatory and immune processes in OSCC. Ingenuity Pathway Analysis (IPA) combined with the LASSO Cox algorithm was used to identify and optimize a crucial gene signature. Metabolomics analysis was performed to identify the important metabolites which linked to the crucial gene signature. The public data TCGA-HNSCC cohort was used to perform the multiple bioinformatic analysis.
These findings identified a FN1-mediated crucial network that was composed of immune-relevant genes (FN1, ACP5, CCL5, COL1A1, THBS1, BCAT1, PLAU, IGF2BP3, TNF, CSF2, CXCL1 and CXCL5) associated with immune infiltration and influences the tumour microenvironment, which may contribute to OSCC tumorigenesis and progression. Moreover, we integrated the relevant genes with altered metabolites identified by metabolic profiling and identified 7 crucial metabolites (Glu-Glu-Lys, Ser-Ala, Ser-Ala, N-(octadecanoyl) sphing-4-enine-1-phosphocholine, N-methylnicotinamide, pyrrhoxanthinol and xanthine) as potential downstream targets of the FN1-associated gene signature in OSCC. Importantly, FN1 expression is positively correlated with immune infiltration levels in HNSCC, which was confirmed at the single-cell level.
Overall, these results revealed the differential genetic and metabolic patterns associated with OSCC tumorigenesis and identified an essential molecular network that plays an oncogenic role in OSCC by affecting amino acid and purine metabolism. These genes and metabolites might, therefore, serve as predictive biomarkers of survival outcomes and potential targets for therapeutic intervention in OSCC.
口腔鳞状细胞癌（OSCC）是一种发病率和死亡率较高的原发性头颈部恶性肿瘤。然而，其肿瘤发生的分子机制尚不完全清楚。
收集 OSCC 及配对癌旁组织样本，进行多组学研究。通过转录组分析揭示 OSCC 中炎症和免疫过程的显著改变。采用 IPA 联合 LASSO Cox 算法识别和优化关键基因特征。代谢组学分析鉴定与关键基因特征相关的重要代谢物。利用公共数据 TCGA-HNSCC 队列进行多种生物信息学分析。
这些发现确定了一个由 FN1 介导的关键网络，该网络由与免疫浸润相关的免疫相关基因（FN1、ACP5、CCL5、COL1A1、THBS1、BCAT1、PLAU、IGF2BP3、TNF、CSF2、CXCL1 和 CXCL5）组成，影响肿瘤微环境，可能有助于 OSCC 的发生和进展。此外，我们将相关基因与代谢组学分析鉴定的代谢物进行整合，确定了 7 个关键代谢物（Glu-Glu-Lys、Ser-Ala、Ser-Ala、N-（十八烷酰基）鞘氨醇-4-烯-1-磷酸胆碱、N-甲基烟酰胺、吡咯并[2,3-F]喹啉-4,9-二酮和黄嘌呤）作为 OSCC 中 FN1 相关基因特征的潜在下游靶点。重要的是，FN1 表达与 HNSCC 中的免疫浸润水平呈正相关，这在单细胞水平上得到了证实。
综上所述，这些结果揭示了与 OSCC 肿瘤发生相关的差异遗传和代谢模式，并确定了一个重要的分子网络，通过影响氨基酸和嘌呤代谢，在 OSCC 中发挥致癌作用。因此，这些基因和代谢物可能成为 OSCC 患者生存结局的预测生物标志物和潜在治疗靶点。
