Identification of Novel Biomarkers and Candidate Drug in Ovarian Cancer

This paper investigates the expression of the CREB1 gene in ovarian cancer (OV) by deeply excavating the gene information in the multiple databases and the mechanism thereof. In short, we found that the expression of the CREB1 gene in ovarian cancer tissue was significantly higher than that of normal ovarian tissue. Kaplan–Meier survival analysis showed that the overall survival was significantly shorter in patients with high expression of the CREB1 gene than those in patients with low expression of the CREB1 gene, and the prognosis of patients with low expression of the CREB1 gene was better. The CREB1 gene may play a role in the occurrence and development of ovarian cancer by regulating the process of protein. Based on differentially expressed genes, 20 small-molecule drugs that potentially target CREB1 with abnormal expression in OV were obtained from the CMap database. Among these compounds, we found that naloxone has the greatest therapeutic value for OV. The high expression of the CREB1 gene may be an indicator of poor prognosis in ovarian cancer patients. Targeting CREB1 may be a potential tool for the diagnosis and treatment of OV.

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The transcription factor FOXA1 induces epithelial ovarian cancer tumorigenesis and progression

Tumor Biology ◽

10.1177/1010428317706210 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831770621 ◽

Cited By ~ 4

Author(s):

Li-Li Wang ◽

Yin-Ling Xiu ◽

Xi Chen ◽

Kai-Xuan Sun ◽

Shuo Chen ◽

...

Keyword(s):

Ovarian Cancer ◽

Transcription Factor ◽

Ovarian Tissue ◽

B Cell Lymphoma ◽

Migration And Invasion ◽

Cancer Tissue ◽

Ovarian Cancer Tissue ◽

Cancer Pathogenesis ◽

E2f Transcription Factor ◽

Induced Apoptosis

FOXA1 (forkhead box A1), a member of the FOXA transcription factor superfamily, plays an important role in tumor occurrence and development. However, the relationship between FOXA1 and ovarian cancer has not been reported. We examined normal ovarian tissue and ovarian cancer tissue and found increased FOXA1 expression in the cancer tissue. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays demonstrated that transfection with small interfering RNA to silence FOXA1 (si-FOXA1) in ovarian cancer cell lines decreased cell proliferation and induced apoptosis and S-phase arrest. In addition, si-FOXA1 transfection inhibited cell migration and invasion. Western blotting showed that si-FOXA1 transfection decreased the levels of YY1-associated protein 1, cyclin-dependent kinase 1, cyclin D1, phosphatidylinositol-3 kinase, E2F transcription factor 1, B-cell lymphoma 2, and vascular endothelial growth factor A protein. Based on these results, we suggest that FOXA1 plays a catalytic role in ovarian cancer pathogenesis and development by affecting the expression of the above-mentioned proteins.

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Clinical Significance of Screening Differential Metabolites in Ovarian Cancer Tissue and Ascites by LC/MS

Frontiers in Pharmacology ◽

10.3389/fphar.2021.701487 ◽

2021 ◽

Vol 12 ◽

Author(s):

Miao Liu ◽

Yu Liu ◽

Hua Feng ◽

Yixin Jing ◽

Shuang Zhao ◽

...

Keyword(s):

Ovarian Cancer ◽

Serum Alkaline Phosphatase ◽

Sebacic Acid ◽

High Expression ◽

Cancer Tissue ◽

Drug Resistant ◽

Hexadecanoic Acid ◽

Ovarian Cancer Tissue ◽

Resistant Group ◽

Cancer Tissues

Tumor cells not only show a vigorous metabolic state, but also reflect the disease progression and prognosis from their metabolites. To judge the progress and prognosis of ovarian cancer is generally based on the formation of ascites, or whether there is ascites recurrence during chemotherapy after ovarian cancer surgery. To explore the relationship between the production of ascites and ovarian cancer tissue, metabolomics was used to screen differential metabolites in this study. The significant markers leading to ascites formation and chemoresistance were screened by analyzing their correlation with the formation of ascites in ovarian cancer and the clinical indicators of patients, and then provided a theoretical basis. The results revealed that nine differential metabolites were screened out from 37 ovarian cancer tissues and their ascites, among which seven differential metabolites were screened from 22 self-paired samples. Sebacic acid and 20-COOH-leukotriene E4 were negatively correlated with the high expression of serum CA125. Carnosine was positively correlated with the high expression of serum uric acid. Hexadecanoic acid was negatively correlated with the high expression of serum γ-GGT and HBDH. 20a,22b-Dihydroxycholesterol was positively correlated with serum alkaline phosphatase and γ-GGT. In the chemotherapy-sensitive and chemotherapy-resistant ovarian cancer tissues, the differential metabolite dihydrothymine was significantly reduced in the chemotherapy-resistant group. In the ascites supernatant of the drug-resistant group, the differential metabolites, 1,25-dihydroxyvitamins D3-26, 23-lactonel and hexadecanoic acid were also significantly reduced. The results indicated that the nine differential metabolites could reflect the prognosis and the extent of liver and kidney damage in patients with ovarian cancer. Three differential metabolites with low expression in the drug-resistant group were proposed as new markers of chemotherapy efficacy in ovarian cancer patients with ascites.

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The relationship between CD204 M2-polarized tumour-associated macrophages (TAMs), tumour-infiltrating lymphocytes (TILs), and microglial activation in glioblastoma microenvironment: a novel immune checkpoint receptor target

Discover Oncology ◽

10.1007/s12672-021-00423-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Maher Kurdi ◽

Badrah Alghamdi ◽

Nadeem Shafique Butt ◽

Saleh Baeesa

Keyword(s):

Microglial Activation ◽

Inverse Correlation ◽

Idh1 Mutation ◽

High Expression ◽

Kaplan Meier ◽

Significant Difference ◽

Tumour Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes ◽

The Relationship ◽

Low Expression

Abstract Background Tumour associated macrophages (TAMs) and tumour infiltrating lymphocytes (TILs) are considered dominant cells in glioblastoma microenvironment. Aim The purpose of this study was to assess the expression of CD204+ M2-polarized TAMs in glioblastomas and their relationship with CD4+TILs, Iba+microglia, and IDH1 mutation. We also exploreed the prognostic value of these markers on the recurrence-free interval (RFI). Methods The expressions of CD204+TAMs, CD4+TILs, and Iba1+microglia were quantitively assessed in 45 glioblastomas using immunohistochemistry. Kaplan–Meier analysis and Cox hazards were used to examine the relationship between these factors. Results CD204+TAMs were highly expressed in 32 tumours (71%) and the remaining 13 tumours (29%) had reduced expression. CD4+TILs were highly expressed in 10 cases (22%) and 35 cases (77.8%) had low expression. There was an inverse correlation between CD204+TAMs and CD4+TILs, in which 85% of tumours had a high expression of CD204+TAMs and a low expression of CD4+TILs. Nevertheless, there was no significant difference in IDH1 mutation status between the two groups (p = 0.779). There was a significant difference in Iba1+microglial activation between IDH1mutant and IDH1wildtype groups (p = 0.031). For cases with a high expression of CD204+TAMs and a low expression of CD4+TILs, there was a significant difference in RFI after treatment with chemoradiotherapy or radiotherapy (p = 0.030). Conclusion Glioblastoma with a dense CD204+TAMs and few CD4+TILs is associated with IDH1wildtype. These findings suggest that TAMs masks tumour cell and suppress T-cell tumoricidal functions via immunomodulatory mechanisms. Blockade of the CD204-TAM receptor may prevent this mechanism and allow the evolution of TILs.

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Evaluation of the expression of the immunosuppressive enzyme – indoleamine 2,3-dioxygenase in ovarian cancer tissue

Menopausal Review ◽

10.5114/pm.2013.36587 ◽

2013 ◽

Vol 3 ◽

pp. 223-227

Author(s):

Ewelina Rogala ◽

Aldona Nowicka ◽

Wiesława Bednarek ◽

Bartłomiej Barczyński ◽

Wanda Piekarczyk ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Tissue ◽

Ovarian Cancer Tissue ◽

Indoleamine 2,3 Dioxygenase

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Proteomic Analysis of Laser Microdissected Ovarian Cancer Tissue with SELDI-TOF MS

Methods in Molecular Biology - Laser Capture Microdissection ◽

10.1007/978-1-61779-163-5_12 ◽

2011 ◽

pp. 155-163 ◽

Cited By ~ 9

Author(s):

Isabelle Cadron ◽

Toon Van Gorp ◽

Philippe Moerman ◽

Etienne Waelkens ◽

Ignace Vergote

Keyword(s):

Ovarian Cancer ◽

Proteomic Analysis ◽

Cancer Tissue ◽

Ovarian Cancer Tissue ◽

Tof Ms

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Promoter Methylation of the MGRN1 Gene Predicts Prognosis and Response to Chemotherapy of High-Grade Serous Ovarian Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.659254 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiao-fei Li ◽

Hai-yan Sun ◽

Tian Hua ◽

Hai-bo Zhang ◽

Yun-jie Tian ◽

...

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Promoter Region ◽

Upstream Region ◽

Platinum Resistance ◽

High Grade ◽

Serous Ovarian Cancer ◽

Kaplan Meier ◽

Response To Chemotherapy ◽

Low Expression

Aberrant DNA methylation is considered to play a critical role in the chemoresistance of epithelial ovarian cancer (EOC). In this study, we explored the relationship between hypermethylation of the Mahogunin Ring Finger 1 (MGRN1) gene promoter and primary chemoresistance and clinical outcomes in high-grade serous ovarian cancer (HGSOC) patients. The MALDI-TOF mass spectrometry assays revealed a strong association between hypermethylation of the MGRN1 upstream region and platinum resistance in HGSOC patients. Spearman’s correlation analysis revealed a significantly negative connection between the methylation level of MGRN1 and its expression in HGSOC. In vitro analysis demonstrated that knockdown of MGRN1 reduced the sensitivity of cells to cisplatin and that expression of EGR1 was significantly decreased in SKOV3 cells with low levels of MGRN1 expression. Similarly, EGR1 mRNA expression was lower in platinum-resistant HGSOC patients and was positively correlated with MGRN1 mRNA expression. Kaplan-Meier analyses showed that high methylation of the MGRN1 promoter region and low expression of MGRN1 were associated with worse survival of HGSOC patients. In multivariable models, low MGRN1 expression was an independent factor predicting poor outcome. Furthermore, low expression of EGR1 was also been confirmed to be significantly related to the poor prognosis of HGSOC patients by Kaplan-Meier. The hypermethylation of the MGRN1 promoter region and low expression of MGRN1 were associated with platinum resistance and poor outcomes in HGSOC patients, probably by altering EGR1 expression.

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The feasibility of storing ovarian tumor cells on databasing paper: establishing a library of ovarian cancer DNA

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2006.00755.x ◽

2007 ◽

Vol 17 (1) ◽

pp. 94-100 ◽

Cited By ~ 8

Author(s):

K. Galaal ◽

M. Meirovitz ◽

R. Hussain ◽

L. Allcroft ◽

N. Sullivan ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Suspension ◽

Direct Sequencing ◽

Genetic Material ◽

Cell Number ◽

Pcr Analysis ◽

Tissue Banks ◽

Cancer Tissue ◽

Ovarian Cancer Tissue ◽

The Stability

The purpose of this study was to assess the feasibility of establishing a library of ovarian cancer nucleic acids using paper matrix by: 1) confirming the stability of DNA stored on paper matrix over a prolonged period of time, 2) determining the amount of genetic material required for storage, and 3) establishing the stability of RNA. Tumor tissue from 66 patients with ovarian cancer was collected intraoperatively, frozen, and dissociated with collagenase and trypsin. A cell suspension was then prepared and spotted onto the paper. The numbers of cells that were stored on the paper were counted using a hemocytometer. The cell suspension was serially diluted and spotted on the paper matrix until the minimum cell number that can be stored and produce a PCR product was determined. PCR, STR genotyping and direct sequencing were performed on tissue stored on the paper matrix. FTA® paper was used as RNA template, and RT PCR converted the RNA to cDNA. Ten to 50 mg of ovarian cancer tissue was stored on FTA® paper. We stored 7 × 104 cells on ISOcode® paper and 18 × 104 cells on FTA® and obtained extractable DNA. PCR analysis on cards with DNA stored 18 months ago enabled us to establish the stability of DNA after storage. RNA was stable for 6 months when stored on FTA® cards. Since genetic material is extractable from the paper matrices after passage of time, it could be a suitable medium for the storage of genetic material in cancer tissue banks.

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Presence of Mycoplasma DNA in Ovarian Cancer Tissue: Detection by PCR-ELISA Technique

Korean Journal of Gynecologic Oncology and Colposcopy ◽

10.3802/kjgoc.1998.9.1.70 ◽

1998 ◽

Vol 9 (1) ◽

pp. 70

Author(s):

Jong Hyeok Kim ◽

Jun Hee Na ◽

Myung Hee Lee ◽

Jae Young Um ◽

Yong Man Kim ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Tissue ◽

Ovarian Cancer Tissue ◽

Elisa Technique

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Mining expression and prognosis of FOLR1 in ovarian cancer by using Oncomine and Kaplan-Meier plotter

Pteridines ◽

10.1515/pteridines-2019-0020 ◽

2019 ◽

Vol 30 (1) ◽

pp. 158-164

Author(s):

Qingyuan Su ◽

Qingyuan Lv ◽

Ruijin Wu

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Ovarian Tumor ◽

Ovarian Tissue ◽

Progression Free Survival ◽

Free Survival ◽

Normal Ovarian Tissue ◽

Oncomine Database ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Objective: To further explore folate receptor 1 (FOLR1) gene expression in ovarian cancer and its association with patients’ prognosis by deep mining the Oncomine and Kaplan-Meier plotter databases. Methods: FOLR1 mRNA expression data of ovarian cancer were retrieved from the Oncomine database and further analyzed by comparing tumor to healthy tissue. The prognostic value of FOLR1 in ovarian cancer was analyzed by Kaplan-Meier Plotter, an online survival analysis database. Results A total of 439 studies were included in the Oncomine database in multiple types of cancers. Of the 439 studies, there were 54 with statistical differences for the expression of FOLR1, 19 with increased expression of FOLR1 and 35 with decreased expression comparing ovarian cancer to normal ovary tissue. After searching the Oncomine database, six datasets were discovered comparing the mRNA expression in ovarian tumor to healthy tissue. FOLR1 mRNA expression in ovarian tumor was significantly higher than that of normal ovarian tissue (all p<0.05). The Kaplan-Meier Plotter database analyzed the correlation between FOLR1 expression and ovarian cancer patient’s prognosis. A significant difference of progression-free survival between FOLR1 high and low expressing groups was found in ovarian cancer patients (HR=1.14, 95%CI: 1.00-1.29, p=0.043). However, the overall survival was not statistically different between high and low FOLR1 expressing patients (HR=0.95, 95%CI: 0.84-1.09, p=0.48). Conclusion FOLR1 mRNA was found to be highly expressed in ovarian tumor compared to normal ovarian tissue. Elevated FOLR1 mRNA expression was associated with the poor progression-free survival.

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