A Long Non-coding RNA Signature to Improve Prognostic Prediction of Pancreatic Ductal Adenocarcinoma

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Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid malignant tumors worldwide. Increasing investigations demonstrate that long non-coding RNAs (lncRNAs) expression is abnormally dysregulated in cancers. It is crucial to identify and predict the prognosis of patients for the selection of further therapeutic treatment.

Methods: PDAC lncRNAs abundance profiles were used to establish a signature that could better predict the prognosis of PDAC patients. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to establish a multi-lncRNA signature in the TCGA training cohort ( N = 107). The signature was then validated in a TCGA validation cohort ( N = 70) and another independent Fudan cohort ( N = 46).

Results: A five-lncRNA signature was constructed and it was significantly related to the overall survival (OS), either in the training or validation cohorts. Through the subgroup and Cox regression analyses, the signature was proven to be independent of other clinic-pathologic parameters. Receiver operating characteristic curve (ROC) analysis also indicated that our signature had a better predictive capacity of PDAC prognosis. Furthermore, ClueGO and CluePedia analyses showed that a number of cancer-related and drug response pathways were enriched in high risk groups.

Conclusions: Identifying the five-lncRNA signature (RP11-159F24.5, RP11-744N12.2, RP11-388M20.1, RP11-356C4.5, CTC-459F4.9) may provide insight into personalized prognosis prediction and new therapies for PDAC patients.

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Gene regulation by the act of long non-coding RNA transcription

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Gender Differences in Cancer Susceptibility: An Inadequately Addressed Issue

M. Tevfik Dorak, Ebru Karpuzoglu (2012)

The gender difference in cancer susceptibility is one of the most consistent findings in cancer epidemiology. Hematologic malignancies are generally more common in males and this can be generalized to most other cancers. Similar gender differences in non-malignant diseases including autoimmunity, are attributed to hormonal or behavioral differences. Even in early childhood, however, where these differences would not apply, there are differences in cancer incidence between males and females. In childhood, few cancers are more common in females, but overall, males have higher susceptibility. In Hodgkin lymphoma, the gender ratio reverses toward adolescence. The pattern that autoimmune disorders are more common in females, but cancer and infections in males suggests that the known differences in immunity may be responsible for this dichotomy. Besides immune surveillance, genome surveillance mechanisms also differ in efficiency between males and females. Other obvious differences include hormonal ones and the number of X chromosomes. Some of the differences may even originate from exposures during prenatal development. This review will summarize well-documented examples of gender effect in cancer susceptibility, discuss methodological issues in exploration of gender differences, and present documented or speculated mechanisms. The gender differential in susceptibility can give important clues for the etiology of cancers and should be examined in all genetic and non-genetic association studies.

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Author and article information

Contributors

Chenhao Zhou: URI : http://loop.frontiersin.org/people/784897/overview

Yue Zhao: URI : http://loop.frontiersin.org/people/720048/overview

Christiane Bruns: URI : http://loop.frontiersin.org/people/721642/overview

Qiongzhu Dong: URI : http://loop.frontiersin.org/people/720466/overview

Journal

Journal ID (nlm-ta): Front Oncol

Journal ID (iso-abbrev): Front Oncol

Journal ID (publisher-id): Front. Oncol.

Title: Frontiers in Oncology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2234-943X

Publication date (Electronic): 08 November 2019

Publication date Collection: 2019

Volume: 9

Electronic Location Identifier: 1160

Affiliations

[1] ¹Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University , Shanghai, China

[2] ²Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University , Shanghai, China

[3] ³Department of Breast Surgery, Zhejiang Cancer Hospital , Zhejiang, China

[4] ⁴Institutes of Biomedical Sciences, Fudan University , Shanghai, China

[5] ⁵Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University , Shanghai, China

[6] ⁶Department of General, Visceral and Cancer Surgery, University Hospital of Cologne , Cologne, Germany

[7] ⁷Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University , Shanghai, China

Author notes

Edited by: Zhaohui Huang, Affiliated Hospital of Jiangnan University, China

Reviewed by: Pieter J. Eichhorn, National University of Singapore, Singapore; Suresh K. Kalangi, Amity University Gurgaon, India

*Correspondence: Huliang Jia jbl-1@ 123456163.com

Ning Ren renning@ 123456fudan.edu.cn

Qiongzhu Dong qzhdong@ 123456fudan.edu.cn

This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology

†These authors have contributed equally to this work

Article

DOI: 10.3389/fonc.2019.01160

PMC ID: 6857660

SO-VID: e6281a06-3d29-4de2-97f9-02dfa57dda1a

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 02 August 2019

Date accepted : 17 October 2019

Page count

Figures: 6, Tables: 2, Equations: 0, References: 49, Pages: 13, Words: 7280

Funding

Funded by: National Key Research and Development Program of China Stem Cell and Translational Research 10.13039/501100013290

Funded by: National Natural Science Foundation of China 10.13039/501100001809

Award ID: 81472672

Funded by: Shanghai International Science and Technology 10.13039/501100009962

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A Long Non-coding RNA Signature to Improve Prognostic Prediction of Pancreatic Ductal Adenocarcinoma

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Karger: Oncology

Most cited references 28

The meaning and use of the area under a receiver operating characteristic (ROC) curve.

Gene regulation by the act of long non-coding RNA transcription

Gender Differences in Cancer Susceptibility: An Inadequately Addressed Issue

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Cited by 14

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