研究动态
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HPV16 阳性宫颈癌中编码和长非编码 RNA 相关表达水平的生物学和临床相关性。

Biological and clinical relevance of correlated expression levels of coding and long noncoding RNAs in HPV16 positive cervical cancers.

发表日期:2024 Aug 29
作者: Abhisikta Ghosh, Abarna Sinha, Arnab Ghosh, Somrita Roy, Sumana Mallick, Vinoth Kumar, Sonia Mathai, Jaydip Bhaumik, Asima Mukhopadhyay, Saugata Sen, Aditi Chandra, Arindam Maitra, Nidhan K Biswas, Partha P Majumder, Sharmila Sengupta
来源: Human Genomics

摘要:

人乳头瘤病毒 (HPV) 驱动宫颈癌 (CaCx) 发病机制,而病毒癌蛋白会危及此类癌症中的整体基因表达。在这项研究中,我们的目的是鉴定差异表达编码 (DEcGs) 和长非编码 RNA 基因 (DElncGs) 特异性感知内含子和天然反义转录本,因为它们位于基因区域,可能对其表达模式产生直接影响。邻近的编码基因。我们通过采用链特异性RNA-seq将HPV16阳性CaCx患者(N = 44)与HPV阴性正常个体(N = 34)进行比较,并确定DEcGs和DElncGs之间的关系及其临床意义。通过对 DEcG 进行基因集富集和蛋白质-蛋白质相互作用 (PPI) 分析,我们确定了对流产病毒生命周期和癌症进展至关重要的过程的富集。 DEcG 形成了 16 个基因簇,我们通过 Cytoscape 的分子复合物检测 (MCODE) 插件对其进行了识别。所有基因簇都描绘了与癌症相关的功能。我们根据 Pearson 相关系数记录了 79 个 DElncG 与近端基因组位点处的 DEcG 的表达水平显着相关。在这些基因对中,有 24 对描述了与正常个体相比,患者之间的相关系数显着改变。其中,6 个此类基因对的 6 个 DEcG 属于 5 个已识别的基因簇,其中之一与生存相关。在 24 个相关的 DEcG:DElncG 对中,我们鉴定了 3 对,其中两个成员的表达与患者的总体生存率显着相关。这些发现证明了这些基因对在患者预测中的合作作用,从而具有巨大的转化潜力。因此,阐明患者和正常样本中配对的 DElncG 和 DEcG 之间的相关强度,可以作为识别 HPV16 阳性 CaCx 的治疗和预后目标的基础。© 2024。作者。
Human papillomavirus (HPV) drives cervical cancer (CaCx) pathogenesis and viral oncoproteins jeopardize global gene expression in such cancers. In this study, our aim was to identify differentially expressed coding (DEcGs) and long noncoding RNA genes (DElncGs) specifically sense intronic and Natural Antisense Transcripts as they are located in the genic regions and may have a direct influence on the expression pattern of their neighbouring coding genes. We compared HPV16-positive CaCx patients (N = 44) with HPV-negative normal individuals (N = 34) by employing strand-specific RNA-seq and determined the relationships between DEcGs and DElncGs and their clinical implications. By performing Gene set enrichment and protein-protein interaction (PPI) analyses of DEcGs, we identified enrichment of processes crucial for abortive virus life cycle and cancer progression. The DEcGs formed 16 gene clusters which we identified through Molecular Complex Detection (MCODE) plugin of Cytoscape. All the gene clusters portrayed cancer-related functions. We recorded significantly correlated expression levels of 79 DElncGs with DEcGs at proximal genomic loci based on Pearson's Correlation coefficients. Of these gene pairs, 24 pairs portrayed significantly altered correlation coefficients among patients, compared to normal individuals. Of these, 6 DEcGs of 6 such gene pairs, belonged to 5 of the identified gene clusters, one of which was survival-associated. Out of the 24 correlated DEcG: DElncG pairs, we identified 3 pairs, where expression of both members was significantly associated with patient overall survival. The findings justify the cooperative roles of these gene pairs, in patient prognostication, thereby bearing immense potential for translation. Thus, elucidation of correlative strengths between paired DElncGs and DEcGs in patient and normal samples, could serve as a foundation for identification of therapeutic and prognostic targets of HPV16-positive CaCx.© 2024. The Author(s).