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外泌体转录组货物及其与 HNSCC 患者生存的功能相关性。

Exosomal transcript cargo and functional correlation with HNSCC patients' survival.

机构信息

Department of Zoology, Molecular Oncology Laboratory, University of Delhi (North Campus), Delhi, 110007, India.

Department of Zoology, Deshbandhu College, University of Delhi, Delhi, India.

出版信息

BMC Cancer. 2024 Sep 13;24(1):1144. doi: 10.1186/s12885-024-12759-9.

Abstract

BACKGROUND

HPV status in a subset of HNSCC is linked with distinct treatment outcomes. Present investigation aims to elucidate the distinct clinicopathological features of HPV-positive and HPV-negative HNSCC and investigate their association with the HNSCC patient survival.

MATERIALS AND METHODS

The total RNA of exosomes from HPV-positive (93VU147T) and HPV-negative (OCT-1) HNSCC cells was isolated, and the transcripts were estimated using Illumina HiSeq X. The expression of altered transcripts and their clinical relevance were further analyzed using publicly available cancer transcriptome data from The Cancer Genome Atlas (TCGA).

RESULTS

Transcriptomic analyses identified 3785 differentially exported transcripts (DETs) in HPV-positive exosomes compared to HPV-negative exosomes. DETs that regulate the protein machinery, cellular redox potential, and various neurological disorder-related pathways were over-represented in HPV-positive exosomes. TCGA database revealed the clinical relevance of altered transcripts. Among commonly exported abundant transcripts, SGK1 and MAD1L1 showed high expression, which has been correlated with poor survival in HNSCC patients. In the top 20 DETs of HPV-negative exosomes, high expression of FADS3, SGK3, and TESK2 correlated with poor survival of the HNSCC patients in the TCGA database.

CONCLUSION

Overall, our study demonstrates that HPV-positive and HPV-negative cells' exosomes carried differential transcripts cargo that may be related to pathways associated with neurological disorders. Additionally, the altered transcripts identified have clinical relevance, correlating with patient survival in HNSCC, thereby highlighting their potential as biomarkers and as therapeutic targets.

摘要

背景

HPV 状态与部分头颈鳞状细胞癌(HNSCC)的独特治疗结果相关。本研究旨在阐明 HPV 阳性和 HPV 阴性 HNSCC 的不同临床病理特征,并研究其与 HNSCC 患者生存的关联。

材料与方法

从 HPV 阳性(93VU147T)和 HPV 阴性(OCT-1)HNSCC 细胞的外泌体中分离总 RNA,并使用 Illumina HiSeq X 估算转录本。使用来自癌症基因组图谱(TCGA)的公共癌症转录组数据进一步分析改变的转录本及其临床相关性。

结果

转录组分析鉴定出 HPV 阳性外泌体与 HPV 阴性外泌体相比有 3785 个差异表达的转移 RNA(DETs)。在 HPV 阳性外泌体中,调节蛋白质机器、细胞氧化还原潜力和各种神经紊乱相关途径的 DETs 过表达。TCGA 数据库揭示了改变的转录本的临床相关性。在常见高表达的外泌体丰度转录本中,SGK1 和 MAD1L1 表达较高,这与 HNSCC 患者的不良预后相关。在 HPV 阴性外泌体的前 20 个 DET 中,FADS3、SGK3 和 TESK2 的高表达与 TCGA 数据库中 HNSCC 患者的不良预后相关。

结论

总的来说,我们的研究表明 HPV 阳性和 HPV 阴性细胞的外泌体携带的差异转录本 cargo 可能与与神经紊乱相关的途径有关。此外,鉴定出的改变的转录本具有临床相关性,与 HNSCC 患者的生存相关,从而突出了它们作为生物标志物和治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3267/11395213/46ca0e001944/12885_2024_12759_Fig1_HTML.jpg

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