Comprehensive Analysis of the Expression of Key Genes Related to Hippo Signaling and Their Prognosis Impact in Ovarian Cancer

The Hippo signaling pathway, one of the most conserved in humans, controlling dimensions of organs and tumor growth, is frequently deregulated in several human malignancies, including ovarian cancer (OC). The alteration of Hippo signaling has been reported to contribute to ovarian carcinogenesis and progression. However, the prognostic roles of individual Hippo genes in OC patients remain elusive. Herein we investigated the expression level and prognostic value of key Hippo genes in OC using online databases, followed by a qRT-PCR validation step in an additional patient cohort. Using the GEPIA database, we observed an increased level for TP53 and reduced expression level for LATS1, LATS2, MST1, TAZ, and TEF in tumor tissue versus normal adjacent tissue. Moreover, LATS1, LATS2, TP53, TAZ, and TEF expression levels have prognostic significance correlated with progression-free survival. The qRT-PCR validation step was conducted in an OC patient cohort comprising 29 tumor tissues and 20 normal adjacent tissues, endorsing the expression level for LATS1, LATS2, and TP53, as well as for two of the miRNAs targeting the TP53 gene, revealing miR-25-3p upregulation and miR-181c-5p downregulation. These results display that there are critical prognostic value dysregulations of the Hippo genes in OC. Our data demonstrate the major role the conserved Hippo pathway presents in tumor control, underlying potential therapeutic strategies and controlling several steps modulated by miRNAs and their target genes that could limit ovarian cancer progression.

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LncRNA SNHG14 Promotes Progression of Ovarian Cancer by Regulating miR-206 Expression

Tobacco Regulatory Science ◽

10.18001/trs.7.5.1.174 ◽

2021 ◽

Vol 7 (5) ◽

pp. 3997-4004

Author(s):

Zhibo Zou ◽

Lin Peng

Keyword(s):

Ovarian Cancer ◽

Flow Cytometry ◽

Cell Proliferation ◽

Tumor Growth ◽

Cancer Progression ◽

Nude Mice ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Qrt Pcr ◽

Research Objects

Objective: This study aimed to probe into the effect of LncRNA SNHG14 on ovarian cancer progression by regulating miR-206.Methods: Fifty-seven ovarian cancer (OC) patients who were treated in our hospital from December 2017 to December 2019 were collected as the research objects. During the operation, OC tissues and paracancerous tissues of patients were collected, and the effect of SNHG14 on OC tumor growth in nude mice was detected, and SNHG14 inhibitor was transfected into OC cells. The relative expression of SNHG14 in tissues and cells was detected by qRT-PCR, cell proliferation was testedvia CCK8, migration and invasion were detected through Transwell, apoptosis was assessedvia flow cytometry, and the targeted relationship between SNHG14 and miR-206 was detected by dual luciferase reporter gene.Results: SNHG14 is highly expressed in OC tissues, cells and nude mice. Down-regulating it can inhibit the biological ability of OC cells and inhibit the growth of nude mice tumors. It can directly target miR-206 to regulate CCND1 expression and promote OC progression.Conclusion: LncRNA SNHG14 can act as miR-206 sponge to regulate CCND1 expression downstream of miR-206 and promote OC progression.

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CD147 in Ovarian and Other Cancers

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182749139 ◽

2013 ◽

Vol 23 (1) ◽

pp. 2-8 ◽

Cited By ~ 12

Author(s):

Hong Yang ◽

Biliang Chen

Keyword(s):

Ovarian Cancer ◽

Older Women ◽

Cancer Progression ◽

Prognostic Value ◽

Prognostic Markers ◽

Current Knowledge ◽

Diagnostic Value ◽

Extracellular Matrix Metalloproteinase Inducer ◽

Gynecological Malignancy ◽

Diagnostic And Prognostic Value

Ovarian cancer, a gynecological malignancy, is the most common cause of death in older women worldwide. The overall 5-year survival of ovarian cancer patients is only 20% because of late diagnosis, as well as distant metastasis and multidrug resistance. Therefore, predictive and prognostic markers are urgently required for the early diagnosis of ovarian cancer. CD147, an extracellular matrix metalloproteinase inducer, is overexpressed in ovarian cancers. Current knowledge suggests that CD147 is associated with the survival and progression of ovarian cancer, and is considered as a biomarker of poor outcome. Here, we specifically review the roles of CD147 in ovarian cancer progression and discuss the diagnostic and prognostic value of CD147 in patients with ovarian cancer. CD147 promotes ovarian cancer progression by its involvement in every facet of malignancy, including invasion, metastasis, survival, angiogenesis, and drug resistance. Although it is not fully confirmed, the combination of CD147 with other biomarkers might be of diagnostic value.

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Transformer 2β Regulates the Alternative Splicing of Cell Cycle Regulator Genes to Promote Ovarian Cancer Cell Progression

10.21203/rs.3.rs-853170/v1 ◽

2021 ◽

Author(s):

Peiying Fu ◽

Ting Zhou ◽

Dong Chen ◽

ShiXuan Wang ◽

Ronghua Liu

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Alternative Splicing ◽

Cancer Progression ◽

Poor Prognosis ◽

Molecular Mechanisms ◽

Rna Binding ◽

Rna Binding Proteins ◽

Expression Level

Abstract Background: Late-stage ovarian cancer (OV) has a poor prognosis and a high metastasis rate, but the underlying molecular mechanism is ambiguous. RNA binding proteins (RBPs) play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis. Results: In this study, we explored the molecular functions of a canonical RBP, TRA2B, in cancer cells. TRA2B knockdown in HeLa cells and whole-transcriptome sequencing (RNA-seq) experiments revealed that the TRA2B-regulated alternative splicing (AS) profile was tightly associated with the mitotic cell cycle, apoptosis, and several cancer pathways. Moreover, hundreds of genes were regulated by TRA2B at the expression level, and their functions were enriched in cell proliferation, cell adhesion and angiogenesis, which are related to cancer progression. We also observed that AS regulation and expression regulation occurred independently by integrating the alternatively spliced and differentially expressed genes. We then explored and validated the carcinogenic functions of TRA2B by knocking down its expression in OV cells. In vivo, a high expression level of TRA2B was associated with a poor prognosis in OV patients. Conclusions: We demonstrated the important roles of TRA2B in ovarian neoplasia and OV progression and identified the underlying molecular mechanisms, facilitating the targeted treatment of OV in the future.

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The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium

Cancers ◽

10.3390/cancers13112613 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2613

Author(s):

Eva Obermayr ◽

Angelika Reiner ◽

Burkhard Brandt ◽

Elena Ioana Braicu ◽

Alexander Reinthaller ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Progression ◽

Residual Disease ◽

Prognostic Significance ◽

Immunofluorescent Staining ◽

Prognostic Impact ◽

Risk Of Recurrence

Introduction: We previously reported the prognostic impact of circulating tumor cells (CTCs) in a multicenter study on minimal residual disease in primary ovarian cancer. With additional follow-up data, we evaluated the combined CTC approach (CTCscombo), in particular for the patients who had survived more than five years. Material and Methods: Blood samples taken at baseline and six months after adjuvant treatment (follow-up) were assessed by quantitative PCR (qPCR) measuring PPIC transcripts and immunofluorescent staining (IF). A positive result with either IF or qPCR was classified as CTCcombo-positive. Further, PPIC was assessed in the primary tumor tissue. Results: The concordance of IF and qPCR was 65% at baseline and 83% after treatment. Results showed that 50.5% of the baseline and 29.5% of the follow-up samples were CTCcombo-positive. CTCscombo after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227–5.398, p = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948–8.498, p < 0.001), and increased mortality after five survived years. Discussion: The two-sided analytical approach revealed CTC subpopulations associated with ovarian cancer progression and may illuminate a potential treatment-related shift in molecular phenotypes. That approach can identify patients who have elevated risk of recurrence and death due to ovarian cancer and who may require risk-adapted treatment strategies.

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Prognostic values of aquaporins mRNA expression in human ovarian cancer

Bioscience Reports ◽

10.1042/bsr20180108 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 3

Author(s):

Mandika Chetry ◽

Saisai Li ◽

Hailing Liu ◽

Xiaoli Hu ◽

Xueqiong Zhu

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Cancer Patients ◽

Prognostic Value ◽

Prognostic Significance ◽

Prognostic Indicators ◽

Transmembrane Channel ◽

Kaplan Meier ◽

Cancer Types ◽

Kaplan Meier Plotter

Aquaporins (AQPs), a family of transmembrane channel, are composed of 13 identified members (AQP0–12). Accumulating evidences reported that AQPs were correlated with various biological roles and represented a prognostic predictor in various cancer types. However, the prognostic value of AQPs expression in ovarian cancer remains unclear. Using ‘Kaplan–Meier plotter’ (KM plotter) online database, we explored the predictive prognostic value of individual AQPs members’ mRNA expression to overall survival (OS) in different clinical data, such as histology, pathological grades, clinical stages, TP53 status, and applied chemotherapy in ovarian cancer patients. Our results revealed that higher AQP0, AQP1, and AQP4 mRNA expression were correlated with poor OS, whereas higher AQP3, AQP5, AQP6, AQP8, AQP10, and AQP11 showed better OS in ovarian cancer patients. Moreover, AQP4 and AQP8 showed poor OS in TP53-mutated ovarian cancer patients and AQP1 presented unfavorable OS in both TP53 mutated and wild ovarian cancer patients. Additionally, AQP3, AQP6, and AQP11 mRNA expression were correlated with better OS, whereas AQP0 and AQP1 showed poor OS in all ovarian cancer patients treated with Platin, Taxol, and Taxol + Platin chemotherapy. AQP5, AQP8, and AQP10 were associated with improved OS, however, AQP4 predicted unfavorable OS in all patients treated with Platin chemotherapy. Our results suggest that individual AQPs, except AQP2 and AQP9, are associated with unique prognostic significance and may thus act as new predictive prognostic indicators and potential drug therapeutic target in ovarian cancer.

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Expression profile of EPHB3 and its prognostic significance in colorectal cancer progression (Running head: Prognostic value of EPHB3 in colorectal cancers)

Annals of Oncology ◽

10.1093/annonc/mdz246.117 ◽

2019 ◽

Vol 30 ◽

pp. v241

Author(s):

B. Jang ◽

H. Kim

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Expression Profile ◽

Prognostic Value ◽

Prognostic Significance ◽

Colorectal Cancers ◽

Colorectal Cancer Progression ◽

Running Head

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Prognostic significance of NDRG2 combined with EGFR patients with lung adenocarcinoma

10.21203/rs.2.14181/v2 ◽

2019 ◽

Author(s):

Bo Yang ◽

Xiao-Ping Li ◽

Hong-Gang Zhou ◽

Tao Jiang ◽

Ting Xiao ◽

...

Keyword(s):

Regression Analysis ◽

Lung Adenocarcinoma ◽

Prognostic Value ◽

Cox Regression ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

Clinicopathological Characteristics ◽

Expression Level ◽

Cox Regression Analysis ◽

Egfr Expression

Abstract Background: N-myc downstream-regulated gene 2 (NDRG2) plays a substantial role in lung adenocarcinoma (LUAD). Epidermal growth factor receptor (EGFR) mutation could significantly improve prognosis in patients with LUAD. In this study, we aimed to elucidate the prognostic value of NDRG2/EGFR in patients with LUAD. Methods: Immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) were conducted to detect the expression levels of NDRG2 protein. Association between NDRG2/EGFR expression and clinicopathological characteristics of patients with LUAD was examined as well. Serum level of carcinoembryonic antigen (CEA) was tested prior to treatment of patients with LUAD. Patients’ overall survival was assessed by Kaplan–Meier method. Multivariate Cox regression analysis was carried out to investigate the effects of patients’ demographic characteristics on OS. Results: The expression level of NDRG2 was significantly decreased in patients with LUAD. The expression level of NDRG2 was positively correlated with levels of CEA and EGFR. Advanced stages were significantly associated with low expression level of NDRG2. We found that patients in NDRG2-high/EGFR(+) group had the best outcome, while patients in NDRG2-low/EGFR(-) group had the worst. Meanwhile, Cox regression analysis showed that NDRG2-low/EGFR(+), NDRG2-high/EGFR(+), and vascular invasion were independent prognostic factors of LUAD. Conclusion: The significant prognostic value of NDRG2/EGFR should be highly considered in patients with LUAD.

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LncRNA SNHG20 predicts a poor prognosis and promotes cell progression in epithelial ovarian cancer

Bioscience Reports ◽

10.1042/bsr20182186 ◽

2019 ◽

Vol 39 (4) ◽

Cited By ~ 5

Author(s):

Dandan Wang ◽

Jianrong Dai ◽

Shunyu Hou ◽

Yonghong Qian

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Progression ◽

Noncoding Rna ◽

Histological Grade ◽

Underlying Mechanism ◽

Cell Counting ◽

Immunofluorescent Staining ◽

Migration And Invasion ◽

Qrt Pcr

AbstractThe long noncoding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to play a crucial role in cancer progression. However, the functions of SNHG20 in epithelial ovarian cancer (EOC) are not well established. The aim of the present study was to investigate SNHG20 clinical significance and its underlying mechanism in proliferation and metastasis in EOC. The expression level of SNHG20 was identified via in situ hybridization (ISH) and quantitative RT-PCR (qRT-PCR). The proliferative and metastatic capacities by silencing SNHG20 expression in A2780 and CAOV-3 cells were measured by cell counting kit-8 (CCK-8) and transwell assays. The molecular mRNA and protein expressions were examined using qRT-PCR, Western blot, and double immunofluorescent staining. SNHG20 expression was markedly higher in serous EOC tissues than that in adjacent tissues and closely correlated with histological grade and lymph node (LN) status. Patients with high SNHG20 showed a shorter overall survival (OS) and SNHG20 was an independent risk factor for the prognosis of serous EOC. Knockdown of SNHG20 remarkably inhibited EOC cell proliferation, migration, and invasion, which was associated with dysregulation of P21, Cyclin D1, E-cadherin, and Vimentin. These results suggest that SNHG20 may serve as an independent prognostic predictor and function as a noncoding oncogene in EOC progression, which might be a possible novel diagnostic marker and treatment target.

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Low Expression of Occludin in the Melanoma Patient

10.30699/ijp.2019.85213.1801 ◽

2019 ◽

Vol 14 (4) ◽

pp. 272-278

Author(s):

Pouri Salehi ◽

Farzaneh Tafvizi ◽

Kambiz Kamyab Hesari

Keyword(s):

Cancer Progression ◽

Mrna Level ◽

Prognostic Significance ◽

Mitotic Count ◽

Expression Level ◽

Sufficient Evidence ◽

Control Group ◽

Computational Technique ◽

Mesenchymal Transition ◽

Significant Difference

Background & Objective: Malignant melanoma is the fatal cutaneous neoplasm which is curable by the early diagnosis. The expression of occludin protein which is an integral membrane protein is altered in an epithelial-to-mesenchymal transition. Although, recent studies provide sufficient evidence supporting the functional importance of occludin in cancer, the prognostic significance of occludin expression levels in melanoma remains obscure. The aim of this study was to determine occludin expression level and itscorrelation with clinicopathological features of the patients with melanoma. Methods: The occludin mRNA level was compared between paraffin-embedded tissues of 40 patients with melanoma and 10 subjects with normal skin. The quality and quantity of the RNA was determined and occludin expression level was measured using Real-time PCR and ∆∆CT computational technique. Results: Theoccludin mRNA level reduced five-fold in the melanoma patients compared to the control group (P=0.000). No significant difference was observed between male and female cases (P=0.533). No significant correlation was observed between occludin mRNA level, mitotic count (P=0.252), and Breslow levels (P=0.171) Conclusion: We can conclude that down-regulation of occludin expression in the patients with melanoma is a hallmark of cancer progression and it might be used as a prognostic factor. No significant correlation was found between occludin gene expression and clinicopathological characteristics including Clark level, Breslow staging, mitotic count, age and gender (P<0.05).

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