Long non-coding RNAs as prognostic markers in human breast cancer

Abstract

Long non-coding RNAs (lncRNAs) have been recently shown to play an important role in gene regulation and normal cellular functions, and disease processes. However, despite the overwhelming number of lncRNAs identified to date, little is known about their role in cancer for vast majority of them. The present study aims to determine whether lncRNAs can serve as prognostic markers in human breast cancer. We interrogated the breast invasive carcinoma dataset of the Cancer Genome Atlas (TCGA) at the cBioPortal consisting of ~ 1,000 cases. Among 2,730 lncRNAs analyzed, 577 lncRNAs had alterations ranging from 1% to 32% frequency, which include mutations, alterations of copy number and RNA expression. We found that deregulation of 11 lncRNAs, primarily due to copy number alteration, is associated with poor overall survival. At RNA expression level, upregulation of 4 lncRNAs (LINC00657, LINC00346, LINC00654 and HCG11) was associated with poor overall survival. A third signature consists of 9 lncRNAs (LINC00705, LINC00310, LINC00704, LINC00574, FAM74A3, UMODL1-AS1, ARRDC1-AS1, HAR1A, and LINC00323) and their upregulation can predict recurrence. Finally, we selected LINC00657 to determine their role in breast cancer, and found that LINC00657 knockout significantly suppresses tumor cell growth and proliferation, suggesting that it plays an oncogenic role. Together, these results highlight the clinical significance of lncRNAs, and thus, these lncRNAs may serve as prognostic markers for breast cancer.

Long intergenic non-coding RNA 271 is predictive of a poorer prognosis of papillary thyroid cancer

“…So far, an overwhelming number of lncRNAs have been identified89, and a certain subset of lncRNAs have been found to play critical roles in oncogenesis and tumor progression10111213. Increasing evidences indicate that, in many types of cancers, lncRNAs are aberrantly expressed and are involved in regulation of diverse biological functions1415161718, suggesting their potential as biomarkers for cancer. Moreover, recent reports181920 have uncovered the potential of lncRNAs as biomarkers for clinical outcomes in many cancers.…”

“…Increasing evidences indicate that, in many types of cancers, lncRNAs are aberrantly expressed and are involved in regulation of diverse biological functions1415161718, suggesting their potential as biomarkers for cancer. Moreover, recent reports181920 have uncovered the potential of lncRNAs as biomarkers for clinical outcomes in many cancers. However, the possible roles and prognostic values of lncRNA signature and specific lncRNAs have not been elucidated clearly in PTC.…”

Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer

“…Liu et al also identified 11 dysregulated lncRNAs, based mainly on their CNAs, which were associated with poor OS in breast cancer. Of these lncRNAs, LINC00657 lncRNA knockout was shown to suppress breast cancer cell growth and proliferation [52], indicating its oncogenic role. Collectively, these data reveal that genetic variants of lncRNAs may serve functional and predictive roles, despite some inconsistent results that urge further study in large cohorts.…”

Comprehensive analysis of lncRNA expression profiles reveals a novel lncRNA signature to discriminate nonequivalent outcomes in patients with ovarian cancer

“…As lncRNAs do not code for proteins, lncRNA expression may be a better indicator of the tumor status, implying the potential and superiority as independent biomarkers for early diagnosis and prognosis prediction in cancers [29]. Currently, several expression-based lncRNA signature have been identified to predict patients' survival in some cancers, including glioblastoma multiforme [30], oesophageal squamous cell carcinoma [31], colorectal cancer [32], breast cancer [33–35], lung cancer [36] and multiple myeloma [37]. Recent studies have revealed that changes in lncRNA expression were associated with OvCa tumorigenesis and metastasis.…”