Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Primary research

Prognostic role of alternative splicing events in head and neck squamous cell carcinoma

Authors: Yanni Ding, Guang Feng, Min Yang

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

Aberrant alternative splicing (AS) is implicated in biological processes of cancer. This study aims to reveal prognostic AS events and signatures that may serve as prognostic predictors for head and neck squamous cell carcinoma (HNSCC).

Methods

Prognostic AS events in HNSCC were identified by univariate COX analysis. Prognostic signatures comprising prognostic AS events were constructed for prognosis prediction in patients with HNSCC. The correlation between the percent spliced in (PSI) values of AS events and the expression of splicing factors (SFs) was analyzed by Pearson correlation analysis. Gene functional annotation analysis was performed to reveal pathways in which prognostic AS is enriched.

Results

A total of 27,611 AS events in 15,873 genes were observed, and there were 3433 AS events in 2624 genes significantly associated with overall survival (OS) for HNSCC. Moreover, we found that AS prognostic signatures could accurately predict HNSCC prognosis. SF-AS regulatory networks were constructed according to the correlation between PSI values of AS events and the expression levels of SFs.

Conclusions

Our study identified prognostic AS events and signatures. Furthermore, it established SF-AS networks in HNSCC that were valuable in predicting the prognosis of patients with HNSCC and elucidating the regulatory mechanisms underlying AS in HNSCC.
Literature
1.
Climente-González H, et al. The functional impact of alternative splicing in cancer. Cell Rep. 2017;20(9):2215–26.PubMedCrossRef
2.
3.
4.
5.
Kozlovski I, et al. The role of RNA alternative splicing in regulating cancer metabolism. Hum Genet. 2017;136(9):1113–27.PubMedCrossRef
6.
7.
Liu C, Guo T, Xu G, Sakai A, Ren S, Fukusumi T, Ando M, Sadat S, Saito Y, Khan Z, Fisch KM. Characterization of alternative splicing events in HPV-negative head and neck squamous cell carcinoma identifies an oncogenic DOCK5 variant. Clin Cancer Res. 2018;24(20):5123–32.PubMedPubMedCentralCrossRef
8.
Liu C, et al. A novel splice variant of LOXL2 promotes progression of human papillomavirus-negative head and neck squamous cell carcinoma. Cancer. 2020;126(4):737–48.PubMedCrossRef
9.
Marur S, et al. Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2016;91(3):386–96.PubMedCrossRef
10.
Budach V, et al. Novel prognostic clinical factors and biomarkers for outcome prediction in head and neck cancer: a systematic review. Lancet Oncol. 2019;20(6):e313–26.PubMedCrossRef
11.
Peitzsch C, et al. Cancer stem cells in head and neck squamous cell carcinoma: identification, characterization and clinical implications. Cancers. 2019;11(5):616.PubMedCentralCrossRef
12.
Ryan M, et al. TCGASpliceSeq a compendium of alternative mRNA splicing in cancer. Nucleic Acids Res. 2016;44(D1):D1018–22.PubMedCrossRef
13.
Conway J, et al. UpSetR: an R package for the visualization of intersecting sets and their properties. Bioinformatics (Oxford, England). 2017;33(18):2938–40.PubMedCentralCrossRef
14.
Engebretsen S, et al. Statistical predictions with glmnet. Clin Epigenet. 2019;11(1):123.CrossRef
15.
Patrick JH, et al. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 2000;56(2):337–44.CrossRef
16.
Kolde R, et al. Robust rank aggregation for gene list integration and meta-analysis. Bioinformatics (Oxford, England). 2012;28(4):573–80.PubMedCentralCrossRef
17.
Piva F, et al. SpliceAid 2: a database of human splicing factors expression data and RNA target motifs. Hum Mutat. 2012;33(1):81–5.PubMedCrossRef
18.
Sveen A, et al. Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes. Oncogene. 2016;35(19):2413–27.PubMedCrossRef
19.
20.
Wong ACH, et al. We skip to work: alternative splicing in normal and malignant myelopoiesis. Leukemia. 2018;32(5):1081–93.PubMedCrossRef
21.
Jin Y, et al. Mutually exclusive alternative splicing of pre-mRNAs. Wiley Interdiscip Rev RNA. 2018;9(3):e1468–e1468.PubMedCrossRef
22.
Xiong Y, et al. Profiles of alternative splicing in colorectal cancer and their clinical significance: a study based on large-scale sequencing data. EBioMedicine. 2018;36:183–95.PubMedPubMedCentralCrossRef
23.
Lin P, et al. Systematic analysis of survival-associated alternative splicing signatures in gastrointestinal pan-adenocarcinomas. EBioMedicine. 2018;34:46–60.PubMedPubMedCentralCrossRef
24.
Zhang Y, et al. Pan-cancer analysis of clinical relevance of alternative splicing events in 31 human cancers. Oncogene. 2019;38(40):6678–95.PubMedCrossRef
25.
Huang Z-G, et al. Prognostic value and potential function of splicing events in prostate adenocarcinoma. Int J Oncol. 2018;53(6):2473–87.PubMedPubMedCentral
26.
Mao S, et al. Survival-associated alternative splicing signatures in esophageal carcinoma. Carcinogenesis. 2019;40(1):121–30.PubMedCrossRef
27.
28.
Zhu G, et al. Prognostic alternative mRNA splicing signature in hepatocellular carcinoma: a study based on large-scale sequencing data. Carcinogenesis. 2019;40(9):1077–85.PubMed
29.
Song J, et al. Systematic analysis of alternative splicing signature unveils prognostic predictor for kidney renal clear cell carcinoma. J Cell Physiol. 2019;234(12):22753–64.PubMedPubMedCentralCrossRef
30.
Yang X, et al. Determining the prognostic significance of alternative splicing events in soft tissue sarcoma using data from The Cancer Genome Atlas. J Transl Med. 2019;17(1):283–283.PubMedPubMedCentralCrossRef
31.
Li Z, et al. Systemic analysis of RNA alternative splicing signals related to the prognosis for head and neck squamous cell carcinoma. Front Oncol. 2020;10:87.PubMedPubMedCentralCrossRef
32.
Li ZX, et al. Comprehensive characterization of the alternative splicing landscape in head and neck squamous cell carcinoma reveals novel events associated with tumorigenesis and the immune microenvironment. Theranostics. 2019;9(25):7648–65.PubMedPubMedCentralCrossRef
33.
34.
Moss T, et al. Comprehensive genomic characterization of upper tract urothelial carcinoma. Eur Urol. 2017;72(4):641–9.PubMedCrossRef
35.
Zeng H, et al. Transcripto-based network analysis reveals a model of gene activation in tongue squamous cell carcinomas. Head Neck. 2019;41(12):4098–110.PubMedCrossRef
36.
Thomas G, et al. Caught in the act—protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease. J Cell Sci. 2017;130(11):1865–76.PubMedPubMedCentralCrossRef
37.
Zhang Y, et al. Identification of a novel RBPMS-ROS1 fusion in an adolescent patient with microsatellite-instable advanced lung adenocarcinoma sensitive to crizotinib: a case report. Clin Lung Cancer. 2019;21(2):e78–83.PubMedCrossRef
38.
Sandanger T, et al. DNA methylation and associated gene expression in blood prior to lung cancer diagnosis in the Norwegian Women and Cancer cohort. Sci Rep. 2018;8(1):16714.PubMedPubMedCentralCrossRef
39.
40.
Hsu F, et al. Signal peptide peptidase promotes tumor progression via facilitating FKBP8 degradation. Oncogene. 2019;38(10):1688–701.PubMedCrossRef
41.
42.
Nakata D, et al. The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation. Biochem Biophys Res Commun. 2017;483(1):271–6.PubMedCrossRef
Metadata
Title
Prognostic role of alternative splicing events in head and neck squamous cell carcinoma
Authors
Yanni Ding
Guang Feng
Min Yang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01249-0

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 Go to the issue

Primary research

Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer

Primary research

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Primary research

Construction of a novel gene-based model for prognosis prediction of clear cell renal cell carcinoma

Primary research

Development and validation of a VHL-associated immune prognostic signature for clear cell renal cell carcinoma

Primary research

Knockdown of DEPDC1B inhibits the development of glioblastoma

Retraction Note

Retraction Note to: Long non-coding RNA LBX2-AS1 enhances glioma proliferation through downregulating microRNA-491-5p
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits