Identification of Novel lncRNAs in Ovarian Cancer and Their Impact on Overall Survival

Int J Mol Sci. 2021 Jan 22;22(3):1079. doi: 10.3390/ijms22031079.

Abstract

Long non-coding RNA's (lncRNA) are RNA sequences that do not encode proteins and are greater than 200 nucleotides in length. They regulate complex cellular mechanisms and have been associated with prognosis in various types of cancer. We aimed to identify lncRNA sequences that are associated with high grade serous ovarian cancer (HGSC) and assess their impact on overall survival. RNA was extracted from 112 HGSC patients and 12 normal fallopian tube samples from our Biobank tissue repository. RNA was sequenced and the Ultrafast and Comprehensive lncRNA detection and quantification pipeline (UClncR) was used for the identification of lncRNA sequences. Univariate logistic and multivariate lasso regression analyses identified lncRNA that was associated with HGSC. Univariate and multivariate Cox proportional hazard ratios were used to evaluate independent predictors of survival. 1943 of 16,325 investigated lncRNA's were differentially expressed in HGSC as compared to controls (p < 0.001). Nine of these demonstrated association with cancer after multivariate lasso regression. Our multivariate analysis of survival identified four lncRNA's associated with survival in HGSC. Three out of these four were found to be independently significant after accounting for all clinical covariates. Lastly, seven lncRNAs were independently associated with initial response to chemotherapy; four portended a worse response, while three were associated with improved response. More research is needed, but there is potential for these lncRNAs to be used as biomarkers of HGSC or predictors of treatment outcome in the future.

Keywords: chemotherapy response; long non-coding RNA; ovarian cancer; overall survival.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biological Specimen Banks
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / mortality
  • Case-Control Studies
  • Fallopian Tubes / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genome, Human
  • Genomics
  • Humans
  • Kaplan-Meier Estimate
  • Multivariate Analysis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics*
  • RNA-Seq
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • RNA, Long Noncoding