Comprehensive analysis of lncRNA-mRNA co-expression patterns identifies immune-associated lncRNA biomarkers in ovarian cancer malignant progression

Guo, Qiuyan; Cheng, Yan; Tian, Li; He, Yanan; Ren, Chengcheng; Sun, Liyuan; Zhang, Guangmei

doi:10.1038/srep17683

Cited by 99 publications

(87 citation statements)

References 34 publications

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“…To our knowledge, the lncRNA expression profiles and OvCa patients derived from TCGA are unprecedented in comprehensiveness and in size, and there is no other available independent datasets to validate our findings. When our study was in progress, two novel immune-associated lncRNAs ( RP11-284N8.3.1 and AC104699.1.1 ) were identified to predict survival of patients with different OvCa stages by using lncRNA-mRNA co-expression network methods [78]. Our study, taken together with Guo's study, highlighted important implications of lncRNAs as novel biomarkers for outcome prediction and therapy decisions.…”

Section: Discussionmentioning

confidence: 87%

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

et al. 2016

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There is growing evidence of dysregulated long non-coding RNAs (lncRNAs) serving as potential biomarkers for cancer prognosis. However, systematic efforts of searching for an expression-based lncRNA signature for prognosis prediction in ovarian cancer (OvCa) have not been made yet. Here, we performed comprehensive analysis for lncRNA expression profiles and clinical data of 544 OvCa patients from The Cancer Genome Atlas (TCGA), and identified an eight-lncRNA signature with ability to classify patients of the training cohort into high-risk group showing poor outcome and low-risk group showing significantly improved outcome, which was further validated in the validation cohort and entire TCGA cohort. Multivariate Cox regression analysis and stratified analysis demonstrated that the prognostic value of this signature was independent of other clinicopathological factors. Associating the outcome prediction with BRCA1 and/or BRCA2 mutation revealed a superior prognosis performance both in BRCA1/2-mutated and BRCA1/2 wild-type tumors. Finally, a significantly correlation was found between the lncRNA signature and the complete response rate of chemotherapy, suggesting that this eight-lncRNA signature may be a measure to predict chemotherapy response and identify platinum-resistant patients who might benefit from other more efficacious therapies. With further prospective validation, this eight-lncRNA signature may have important implications for outcome prediction and therapy decisions.

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Section: Discussionmentioning

confidence: 87%

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

et al. 2016

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“…Recent studies have focused on the role of lncRNAs in human tumors [11], which are noncoding RNAs with a length > 200 nucleotides that differ from small non-coding RNAs, such as miRNA, tRNA, and rRNA [12]. Antisense lncRNAs are the reverse complementary sequences of endogenous RNA and account for approximately 60% lncRNAs, which represents a large proportion of long chain non-coding transcriptomes [13]. MALAT1 can enhance the characteristics of glioma stem cells, which is related to the progression and poor prognosis of glioblastomas [14].…”

Section: Introductionmentioning

confidence: 99%

LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway

Chen

Huang

Sun

et al. 2018

Cell Physiol Biochem

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Background/Aims: LncRNAs have been reported to be vital regulators of the progression of osteosarcoma, although the underlying mechanisms are not completely understood. Methods: The levels of MALAT1 and miR-129-5p expression were measured using qRT-PCR. Cell growth was determined using the CCK-8 and colony formation assays. Cell migration and invasion were detected using the wound healing and Transwell invasion assays, respectively. Tumor growth was determined with a xenograft model. Results: MALAT1 was significantly up-regulated in osteosarcoma tissues compared with adjacent non-tumor soft tissues. Overexpression of MALAT1 promoted osteosarcoma cell proliferation, migration, and invasion in vitro and enhanced tumor growth in a tumor xenograft mouse model. MALAT1 promoted osteosarcoma progression by modulating stem cell-like properties. Moreover, rescue experiment and luciferase reporter assay results indicated that MALAT1 modulates RET expression by sponging miR-129-5p in osteosarcomas. Furthermore, MALAT1 augmented the expression of downstream proteins of the RET-Akt pathway. MALAT1 was consistently significantly increased in osteosarcoma tissues and MALAT1 expression was positively correlated with tumor size and metastasis. High expression of MALAT1 was significantly associated with poor outcomes in patients with osteosarcomas. MALAT1 expression was positively related to RET and negatively related to miR-129-5p in osteosarcoma samples and xenograft tumors. MALAT1 functioned as an oncogenic lncRNA in osteosarcomas and was as an independent prognostic indicator. Conclusion: Our data revealed for the first time that MALAT1 increases stem cell-like properties by up-regulating RET via sponging miR-129-5p, and thus activates the PI3K-Akt signaling pathway and provides potential therapeutic targets for osteosarcoma treatment.

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“…Zhou et al 21 identified an eight-lncRNA signature that can be used to classify patients with poor and improved overall survival rates. Two immune-related lncRNAs, namely, RP11-284N8.3.1 and AC104699.1.1, have been identified as predictors of an ovarian cancer patient’s survival rates by using lncRNA–mRNA coexpression network methods 22 . Similar to protein-coding genes and miRNAs, lncRNAs can be utilized as biomarkers for diagnosis and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients

Liu

Zeng

Zhou

et al. 2017

Sci Rep

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Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinumresistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.Ovarian cancer yields the highest mortality rate of all lethal gynecologic cancers and represents approximately 3% of all cancers diagnosed in women worldwide 1,2 . The prognosis of ovarian cancer is unsatisfactory, with a 5-year survival rate of approximately 30% 3 . Approximately 70% of patient deaths are advanced stage and high-grade serous ovarian cancers (HGS-OvCa) 4 . Despite advancements in surgery and chemotherapy, platinum-resistant cancer recurs in approximately 25% of patients within 6 months after they undergo initial standard treatments consisting of aggressive surgery and platinum-based chemotherapy 5 . Some patients with a complete response to first-line chemotherapy develop acquired drug resistance 6 . Several molecular mechanisms, including drug efflux and tolerance, increased DNA repair, and increased cellular glutathione levels 7-9 , are implicated in chemosensitivity. However, exact mechanisms have yet to be fully investigated. Clinical biomarkers that accurately predict sensitivity to chemotherapy have yet to be developed 10,11 . These factors should be understood to identify prognostic signatures, which can be utilized to develop effective treatment modalities for stratified patients who unlikely respond to platinum-based chemotherapy and thus can benefit from alternative strategies 10 .Dysregulated and functional long noncoding RNAs (lncRNAs) are associated with the tumorigenesis and progression of various human cancers [12][13][14] . lncRNAs are mRNA-like transcripts range from 200 nucleotides (bp) to multiple kilobases (kb) in length but lack ...

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Comprehensive analysis of lncRNA-mRNA co-expression patterns identifies immune-associated lncRNA biomarkers in ovarian cancer malignant progression

Cited by 99 publications

References 34 publications

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

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

LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway

Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients

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