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Investigational New Drugs

, Volume 36, Issue 2, pp 187–194 | Cite as

Systematic analysis reveals a lncRNA-mRNA co-expression network associated with platinum resistance in high-grade serous ovarian cancer

  • Lei Fang
  • Hao Wang
  • Peiling Li
PRECLINICAL STUDIES

Summary

Resistance to platinum-based chemotherapy is the major barrier to treating high-grade serous ovarian cancer (HGS-OvCa). To improve HGS-OvCa patient prognosis, it is critical to identify the underlying mechanisms that promote platinum resistance. The goal of the present study was to identify a lncRNA-mRNA co-expression network and key lncRNAs that predict resistance to platinum-based chemotherapy in ovarian cancer patients. By systematically analyzing the expression profiles of lncRNAs and mRNAs in HGS-OvCa samples from the Cancer Genome Atlas (TCGA), we revealed that lncRNAs play important roles in platinum resistance in HGS-OvCa patients and delineate a lncRNA-mRNA co-expression network in HGS-OvCa patients who exhibit platinum resistance. Within the platinum resistance-specific lncRNA-mRNA network, 35 lncRNAs and 270 mRNAs showed 124 significant lncRNA-mRNA co-expression relationships. Pathway analysis revealed that lncRNAs in the platinum resistance network may participate in platinum resistance by regulating metabolic pathways. Moreover, HGS-OvCa patients with low lncRNA RP5-1120P11.1 expression showed a poorer prognosis than those with high lncRNA RP5-1120P11.1 expression in TCGA dataset (P = 2.74 × 10−5, log rank test), which was also validated in the GSE63885 dataset (P = 0.0242, log rank test). Network and function analysis revealed that lncRNA RP5-1120P11.1 regulates many cancer-related signaling pathways, such as the PI3K-AKT signaling pathway (P = 1.02 × 10−5, hypergeometric test) and the Jak-STAT signaling pathway (P = 1.71 × 10−4, hypergeometric test). Particularly, lncRNA RP5-1120P11.1 expression is significantly positively correlated with ABCC10 gene expression (P = 3.89 × 10−3, Pearson correlation test). Both lncRNA RP5-1120P11.1 and ABCC10 were down-regulated in platinum-resistant HGS-OvCa patients, and RP5-1120P11.1 is located near ABCC10 on chromosome 6. Gene ABCC10 has been implicated in resistance to docetaxel treatment. The present study paves the way for investigating lncRNA functions in platinum drug resistance and identifying lncRNAs with prognostic and therapeutic potential in HGS-OvCa.

Keywords

lncRNAs BRCA1 BRCA2 Prognosis Ovarian cancer 

Abbreviations

CR

Complete response

DEG

Differential expression gene

HR

Hazard ratio

HGS-OvCa

High-grade serous ovarian cancer

OS

Overall survival

TCGA

The cancer genome atlas

TANRIC

The Atlas of non-coding RNAs in cancer

Notes

Acknowledgments

The authors appreciate the efforts of all of researchers who have contributed the data to the public databases of TCGA, TANRIC and GEO. The interpretation and reporting of these data are the sole responsibility of the authors.

Author contributions

Peiling Li conceived, designed, and supervised the overall study. Lei Fang and Hao Wang conducted data processing and computational analyses. Lei Fang and Peiling Li drafted the manuscript. All authors read and approved the final manuscript.

Funding

This work was supported by The Health and Family Planning Commission Scientific Research of Heilongjiang Province [No. 2017–075].

Compliance with ethical standards

Consent for publication

All authors have provided consent for the publication of this manuscript in Investigational New Drugs.

Availability of data and materials

The datasets supporting the conclusions of this article are included within this manuscript.

Competing interests

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyThe Second Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China

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