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PRINS长链非编码RNA是头颈部鳞状细胞癌人乳头瘤病毒感染及预后的新型生物标志物候选物。

PRINS lncRNA Is a New Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas.

作者信息

Kopczyńska Magda, Kolenda Tomasz, Guglas Kacper, Sobocińska Joanna, Teresiak Anna, Bliźniak Renata, Mackiewicz Andrzej, Mackiewicz Jacek, Lamperska Katarzyna

机构信息

Laboratory of Cancer Genetics, Greater Poland Cancer Centre, 15 Garbary Street, Room 5025, 61-866 Poznan, Poland.

Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, 8 Rokietnicka Street, 60-806 Poznan, Poland.

出版信息

Diagnostics (Basel). 2020 Sep 28;10(10):762. doi: 10.3390/diagnostics10100762.

Abstract

Numerous studies have shown that human papillomavirus (HPV) infection is one of the important risk factors for head and neck squamous cell carcinoma (HNSCC) progression and affects the expression of multiple genes, which might serve as new biomarkers. This study examines the effects of HPV infection on long non-coding RNA (lncRNA) expression and the immune system, particularly PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). The Cancer Genome Atlas (TCGA) expression data for lncRNA genes and clinical data were analyzed by GraphPad Prism 5/7. The expressions of PRINS, CDKN2B-AS1, TTTY14, TTTY15, MEG3, and H19 were significantly different in HPV-positive and HPV-negative patients. HPV-positive patients with high PRINS expression demonstrated significantly better overall survival (OS) and disease-free survival (DFS). HPV-positive patients with high PRINS expression showed changes in gene expression associated with immune and antiviral responses. A majority of HPV-positive patients with high PRINS expression demonstrated a high number of immune cells within tumors. PRINS expression was significantly associated with HPV-infection HNSCC tumors. Validation of these results using data set from Gene Expression Omnibus (GEO) indicated that PRINS is upregulated in HPV active infections and in "atypical 1 (IR)" HNSCC clusters, negatively influencing patients' overall survival. Patients with high PRINS expression display different immunological profiles than those with low expression levels. For instance, they have active HPV infection status or are clustered in the "atypical 1 (IR)" subtype of HNSCC which influences both viral infection and patients' survival. It is likely that PRINS could be used as a potential biomarker for HNSCC patients, but its role is dual. On the one hand, it stimulates patients' immune response, while on the other it can be favorable in virus replication.

摘要

大量研究表明,人乳头瘤病毒(HPV)感染是头颈部鳞状细胞癌(HNSCC)进展的重要危险因素之一,且会影响多个基因的表达,这些基因可能成为新的生物标志物。本研究探讨了HPV感染对长链非编码RNA(lncRNA)表达及免疫系统的影响,尤其是对PRINS(应激诱导的银屑病易感性相关RNA基因)的影响。通过GraphPad Prism 5/7分析了癌症基因组图谱(TCGA)中lncRNA基因的表达数据和临床数据。PRINS、CDKN2B-AS1、TTTY14、TTTY15、MEG3和H19在HPV阳性和阴性患者中的表达存在显著差异。PRINS高表达的HPV阳性患者总体生存率(OS)和无病生存率(DFS)显著更高。PRINS高表达的HPV阳性患者显示出与免疫和抗病毒反应相关的基因表达变化。大多数PRINS高表达的HPV阳性患者肿瘤内有大量免疫细胞。PRINS表达与HPV感染的HNSCC肿瘤显著相关。使用基因表达综合数据库(GEO)的数据集对这些结果进行验证表明,PRINS在HPV活跃感染和“非典型1(IR)”HNSCC簇中上调,对患者的总体生存产生负面影响。PRINS高表达的患者与低表达水平的患者表现出不同的免疫特征。例如,他们具有活跃的HPV感染状态,或聚集在HNSCC的“非典型1(IR)”亚型中,这既影响病毒感染,也影响患者的生存。PRINS很可能可作为HNSCC患者的潜在生物标志物,但其作用具有双重性。一方面,它刺激患者的免疫反应,另一方面,它可能有利于病毒复制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d1/7599931/3bc8be81b95d/diagnostics-10-00762-g001.jpg

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