Upregulated long non-coding RNAs TMPO-AS1, DDX11-AS1, and POLE gene expression predict poor prognosis in head and neck squamous cell carcinoma (HNSCC)

IF 1 Q4 GENETICS & HEREDITY Gene Reports Pub Date : 2024-05-31 DOI:10.1016/j.genrep.2024.101942

Mahnoosh Mokhtarinejad , Maryam Pirhoushiaran , Roozbeh Heidarzadehpilehrood , Sara Hesami , Farid Azmoudeh-Ardalan , Abbas Shakoori Farahani

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Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) is prevalent and highly aggressive. HNSCC pathogenesis is characterized by the presence of long non-coding RNAs (lncRNAs) that lead to abnormal cellular functions such as proliferation, migration, and invasion.

Methods

This study examined the expression levels of lncRNAs TMPO-AS1, DDX11-AS1, and the POLE gene in 100 HNSCC tumors and normal adjacent tumors (NATs). The analysis was performed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on fresh-frozen samples.

Results

In HNSCC samples, tumor tissue exhibited markedly elevated levels of POLE expression compared to NATs (p < .001, 95 % CI: 2.410–3.170 vs. 0.9834–1.549). DDX11-AS1 expression was also significantly higher in HNSCC samples than in NATs (p < .001, 95 % CI: 1.879–3.250 vs. 1.029–1.731). Similarly, TMPO-AS1 levels were significantly elevated in HNSCC samples compared to NATs (p < .001, 95 % CI: 1.903–2.639 vs. 0.894–1.329). ROC curve diagnostic analyses revealed AUC values of 0.838 (95 % CI: 0.761–0.915) for POLE, 0.689 (95 % CI: 0.585–0.793) for DDX11-AS1, and 0.808 (95 % CI: 0.724–0.893) for TMPO-AS1. Notably, a substantial association was found between tumor grade and human papillomavirus levels with POLE and TMPO-AS1. Additionally, significant associations were observed between tumor stage and metastasis with DDX11-AS1 and TMPO-AS1 levels. Our findings further investigate a remarkable association between the combined effect of smoking and HPV positive infections and expression levels of POLE, DDX11-AS1, and TMPO-AS1. Our final results align with those from The Cancer Genome Atlas (TCGA), which included 520 HNSCC cases and 44 controls.

Conclusions

Our data emphasize the potential significance of DDX11-AS1, TMPO-AS1, and POLE in the poor prognosis of HNSCC, indicating their contribution to tumor growth and progression.

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长非编码 RNA TMPO-AS1、DDX11-AS1 和 POLE 基因表达上调可预测头颈部鳞状细胞癌 (HNSCC) 的不良预后

背景头颈部鳞状细胞癌（HNSCC）发病率高且侵袭性强。本研究检测了100例HNSCC肿瘤和正常邻近肿瘤（NATs）中lncRNAs TMPO-AS1、DDX11-AS1和POLE基因的表达水平。结果在 HNSCC 样本中，与 NATs 相比，肿瘤组织的 POLE 表达水平明显升高（p < .001, 95 % CI: 2.410-3.170 vs. 0.9834-1.549）。HNSCC 样本中 DDX11-AS1 的表达也明显高于 NATs（p < .001, 95 % CI: 1.879-3.250 vs. 1.029-1.731）。同样，与 NATs 相比，HNSCC 样本中的 TMPO-AS1 水平也明显升高（p < .001, 95 % CI: 1.903-2.639 vs. 0.894-1.329）。ROC 曲线诊断分析显示，POLE 的 AUC 值为 0.838（95 % CI：0.761-0.915），DDX11-AS1 为 0.689（95 % CI：0.585-0.793），TMPO-AS1 为 0.808（95 % CI：0.724-0.893）。值得注意的是，肿瘤分级和人类乳头瘤病毒水平与 POLE 和 TMPO-AS1 有很大关联。此外，在肿瘤分期和转移与 DDX11-AS1 和 TMPO-AS1 水平之间也发现了明显的关联。我们的研究结果进一步探讨了吸烟和人乳头瘤病毒阳性感染的综合效应与 POLE、DDX11-AS1 和 TMPO-AS1 表达水平之间的显著关联。结论我们的数据强调了DDX11-AS1、TMPO-AS1和POLE在HNSCC不良预后中的潜在意义，表明它们对肿瘤的生长和进展做出了贡献。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.