Department of Periodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, P.R. China.
Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
Cancer Genomics Proteomics. 2023 Nov-Dec;20(6):602-616. doi: 10.21873/cgp.20409.
BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has a poor prognosis. Periodontitis, or tooth loss, is considered to be related to hepatocarcinogenesis and its poor prognosis. This study aimed to explore potential associations and cross-talk mechanisms between periodontitis and HCC.
Periodontitis and HCC microarray datasets were acquired from the Gene Expression Omnibus (GEO) database and were analyzed to obtain differentially expressed (DE) lncRNAs, miRNAs and mRNAs. Functional enrichment analysis was used to detect the functions of these mRNAs. Then, a ceRNA network of periodontitis-related HCC was constructed. Least absolute shrinkage and selection operator (LASSO) regression, random forest algorithm, and support vector machine-recursive feature elimination (SVM-RFE) were performed to explore the diagnostic significance of mRNAs in periodontitis-related HCC. Cox regression analyses were conducted to screen mRNAs with prognostic significance in HCC. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were conducted to validate the expression of these mRNAs in HCC tissues.
A ceRNA network was constructed. Functional enrichment analysis indicated that the network is associated with immune and inflammatory responses, the cell cycle and liver metabolic function. LASSO, random forest algorithm and SVM-RFE showed the diagnostic significance of DE mRNAs in HCC. Cox regression analyses revealed that MSH2, GRAMD1C and CTHRC1 have prognostic significance for HCC, and qRT-PCR and IHC validated this finding.
Periodontitis may affect the occurrence of HCC by changing the immune and inflammatory response, the cell cycle and liver metabolic function. MSH2, GRAMD1C and CTHRC1 are potential prognostic biomarkers for HCC.
背景/目的：肝细胞癌（HCC）是最常见的原发性肝癌，预后不良。牙周炎或牙齿缺失被认为与肝癌的发生及其不良预后有关。本研究旨在探讨牙周炎与 HCC 之间的潜在关联和相互作用机制。
从基因表达综合数据库（GEO）中获取牙周炎和 HCC 的微阵列数据集，并进行分析以获得差异表达（DE）的 lncRNA、miRNA 和 mRNA。功能富集分析用于检测这些 mRNA 的功能。然后构建牙周炎相关 HCC 的 ceRNA 网络。采用最小绝对收缩和选择算子（LASSO）回归、随机森林算法和支持向量机递归特征消除（SVM-RFE）探讨 mRNA 在牙周炎相关 HCC 中的诊断意义。进行 Cox 回归分析以筛选在 HCC 中具有预后意义的 mRNA。采用定量实时 PCR（qRT-PCR）和免疫组织化学（IHC）验证这些 mRNA 在 HCC 组织中的表达。
构建了 ceRNA 网络。功能富集分析表明，该网络与免疫和炎症反应、细胞周期和肝脏代谢功能有关。LASSO、随机森林算法和 SVM-RFE 显示了 DE mRNA 在 HCC 中的诊断意义。Cox 回归分析显示，MSH2、GRAMD1C 和 CTHRC1 对 HCC 具有预后意义，qRT-PCR 和 IHC 验证了这一发现。
牙周炎可能通过改变免疫和炎症反应、细胞周期和肝脏代谢功能来影响 HCC 的发生。MSH2、GRAMD1C 和 CTHRC1 可能是 HCC 的潜在预后生物标志物。
