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Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high?grade ovarian serous cancer.

ABSTRACT: High?grade ovarian serous cancer is known for its high rates of invasion and metastasis, and resultant high mortality rate. Therefore, research concerning biomarkers and underlying molecular mechanisms of high?grade ovarian serous cancer progression and prognosis are urgently required. Long non?coding RNAs (lncRNAs) have been the subject of an increasing number of studies, and certain lncRNAs have been demonstrated to serve an important function in the development and progression of various cancers, including HOX transcript antisense RNA, competing endogenous lncRNA 2 for microRNA let?7b, urothelial cancer associated 1, and H19, imprinted maternally expressed transcript (non?protein coding). However, few studies have investigated the differential expression of lncRNAs in high?grade ovarian serous cancer. In the present study, differences in lncRNA and mRNA expression profiles between high?grade ovarian serous cancer tissue samples and healthy fallopian tube tissue samples were investigated using microarray analysis, and the differential expression of lncRNAs and mRNAs was confirmed by reverse transcription?quantitative polymerase chain reaction (RT?qPCR). Then, five abnormally expressed lncRNAs were selected, and the associations between these lncRNAs and ovarian cancer clinicopathological parameters were examined using RT?qPCR. The expression profiles of certain lncRNAs and mRNAs were confirmed to be altered between high?grade ovarian serous cancer tissues and healthy fallopian tube tissues. Furthermore, the expression levels of selected lncRNAs were associated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. These lncRNAs and mRNAs may therefore be involved in the pathogenesis of high?grade ovarian serous cancer. The results of the present study provide an experimental foundation for further exploration of the value of these lncRNAs and mRNAs in the early diagnosis and treatment of high?grade ovarian serous cancer.

SUBMITTER: Lou Y

PROVIDER: S-EPMC5979786 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high‑grade ovarian serous cancer.

Lou Yanhui Y Jiang Huanhuan H Cui Zhumei Z Wang Xiangyu X Wang Lingzhi L Han Yi Y

International journal of molecular medicine 20180323 1

High‑grade ovarian serous cancer is known for its high rates of invasion and metastasis, and resultant high mortality rate. Therefore, research concerning biomarkers and underlying molecular mechanisms of high‑grade ovarian serous cancer progression and prognosis are urgently required. Long non‑coding RNAs (lncRNAs) have been the subject of an increasing number of studies, and certain lncRNAs have been demonstrated to serve an important function in the development and progression of various canc ...[more]

PMID: 29577163

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Project description:BACKGROUND:High-grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian cancer. A growing body of evidence suggests tumor-supporting roles of several members of the kallikrein-related peptidase (KLK) family, including KLK5 and KLK7, in this cancer subtype. In normal physiology, KLK5 and KLK7 are the major proteases involved in skin desquamation. Moreover, in several cancer types KLK5 and KLK7 co-expression has been observed. Recently, we have shown that elevated KLK5 mRNA levels are associated with an unfavorable prognosis in HGSOC. Therefore, the aim of this study was to investigate the clinical significance of KLK7 mRNA expression and to explore its relation to KLK5 levels in HGSOC. METHODS:mRNA expression levels of KLK7 were quantified by qPCR in a well-characterized patient cohort afflicted with advanced high-grade serous ovarian cancer (FIGO III/IV, n?=?139). Previously determined KLK5 mRNA as well as KLK5 and KLK7 antigen concentrations were used to evaluate the relationship between the expression patterns of both factors on the mRNA as well as protein level in tumor tissue of HGSOC patients. RESULTS:There were strong, significant positive correlations between KLK5 and KLK7 both at the mRNA and the protein level, suggesting coordinate expression of these proteases in HGSOC. In univariate analyses, elevated KLK7 levels as well as the combination of KLK5?+?KLK7 (high and/or high versus low/low) were significantly associated with worse progression-free survival (PFS). High mRNA expression levels of KLK7 and the combination of KLK5 and KLK7 showed a trend towards significance for overall survival (OS). In multivariate analyses, KLK7 mRNA expression represented an unfavorable, statistically significant independent predictor for PFS and OS. CONCLUSIONS:The findings imply that both increased KLK5 and KLK7 mRNA expression levels represent unfavorable prognostic biomarkers in advanced high-grade serous ovarian cancer, whereby multivariate analyses indicate that KLK7 mRNA exhibits a stronger predictive value as compared to KLK5 mRNA and the combination of KLK5 and KLK7.

Dataset Information

Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high?grade ovarian serous cancer.

Publications

Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high‑grade ovarian serous cancer.

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