Jiangsu Key Laboratory of Oral Disease, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, China.
Depatment of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
J Oral Pathol Med. 2022 Feb;51(2):160-171. doi: 10.1111/jop.13261. Epub 2021 Dec 1.
miRNAs and mRNAs have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop the pivotal miRNA biomarkers-based prognostic signature for salivary adenoid cystic carcinoma.
The miRNA and mRNA expression data were integrated from the gene expression omnibus database to study their involvement in salivary adenoid cystic carcinoma development and progression. Gene ontology and kyoto encyclopedia of genes and genomes were conducted to analyze the biological pathways. Reverse transcription-quantitative PCR was used to verify the expression of selected miRNAs in salivary adenoid cystic carcinoma and corresponding normal tissues.
There were 386 differentially expressed genes: 158 upregulated and 228 downregulated genes and 102 differentially expressed miRNAs: 78 upregulated and 24 downregulated miRNAs in the salivary adenoid cystic carcinoma samples. A miRNA-mRNA network containing 11 miRNAs and 199 genes was subsequently constructed. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the genes targeted by the 11 miRNAs were mostly involved in tumor-related pathways and processes, such as miRNAs in cancer, focal adhesion, neurotrophin signaling pathway, and the PI3K-Akt signaling pathway. Among them, 4 miRNAs (miR-375, miR-494, miR-34c-5p, and miR-331-3p) were selected to verify by reverse transcription-quantitative PCR in 36 pairs of collected salivary adenoid cystic carcinoma and adjacent nontumor samples. Overall survival analysis revealed that the higher expression of miR-331-3p was significantly associated with a worst overall survival and multivariate Cox regression analysis suggested that hsa-miR-331-3p could be an independent prognostic factor for salivary adenoid cystic carcinoma.
Our results revealed that 4-miRNAs signature was a powerful prognostic biomarker for salivary adenoid cystic carcinoma, which provide a basis for exploring deeper mechanisms regarding the progression of salivary adenoid cystic carcinoma, and leading to the development of potential therapeutic strategies.
miRNAs 和 mRNAs 已被证明与肿瘤发生密切相关，并成为人类癌症有前途的预后生物标志物。因此，本研究旨在开发基于关键 miRNA 生物标志物的唾液腺腺样囊性癌预后签名。
从基因表达综合数据库中整合 miRNA 和 mRNA 表达数据，以研究它们在唾液腺腺样囊性癌发生和进展中的作用。进行基因本体论和京都基因与基因组百科全书分析以分析生物学途径。逆转录定量 PCR 用于验证选定的 miRNA 在唾液腺腺样囊性癌和相应正常组织中的表达。
唾液腺腺样囊性癌样本中存在 386 个差异表达基因：158 个上调基因和 228 个下调基因，以及 102 个差异表达 miRNA：78 个上调 miRNA 和 24 个下调 miRNA。随后构建了一个包含 11 个 miRNA 和 199 个基因的 miRNA-mRNA 网络。基因本体论和京都基因与基因组百科全书富集分析表明，11 个 miRNA 靶向的基因主要参与肿瘤相关途径和过程，如癌症中的 miRNA、焦点粘附、神经营养素信号通路和 PI3K-Akt 信号通路。其中，miR-375、miR-494、miR-34c-5p 和 miR-331-3p 这 4 个 miRNA 通过逆转录定量 PCR 在 36 对收集的唾液腺腺样囊性癌和相邻非肿瘤样本中进行验证。总体生存分析表明，miR-331-3p 的高表达与最差的总体生存显著相关，多变量 Cox 回归分析表明 hsa-miR-331-3p 可能是唾液腺腺样囊性癌的独立预后因素。
我们的结果表明，4-miRNA 特征是唾液腺腺样囊性癌的有力预后生物标志物，为探索唾液腺腺样囊性癌进展的更深层次机制提供了依据，并为潜在的治疗策略的发展提供了依据。
