scholarly journals Overexpression of ICAM-1 Predicts Poor Survival in High-Grade Serous Ovarian Carcinoma: A Study Based on TCGA and GEO Databases and Tissue Microarray

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Shasha Wang ◽  
Can Yin ◽  
Ying Zhang ◽  
Lu Zhang ◽  
Lin Tao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Adhesion Molecule ◽  
Poor Prognosis ◽  
Prognostic Biomarker ◽  
The Cancer Genome Atlas ◽  
High Grade ◽  
Poor Survival ◽  
Serous Ovarian Carcinoma

Intercellular cell adhesion molecule-1 (ICAM-1), an important adhesion molecule in the immunoglobulin superfamily, is expressed on many cell types. Recent studies have identified ICAM-1 as a potential oncogene that promotes the development of epithelial ovarian cancer (EOC); it was also found to be associated with poor survival. However, the clinical significance of its expression in high-grade serous ovarian carcinoma (HGSOC) is unclear. Thus, this study aimed to investigate the significance of ICAM-1 expression in HGSOC. Data on ICAM1 expression and mutations in serous ovarian carcinoma (SOC) were obtained from the Cancer Genome Atlas (TCGA), and ICAM1 mRNA expression data in HGSOC were obtained from the Gene Expression Omnibus (GEO) database. ICAM-1 expression was evaluated by immunohistochemistry in HGSOC and normal fallopian tube tissues microarray. In TCGA data, amplification/mutation of ICAM1 was identified in 12% of serous ovarian carcinoma samples, and overexpression of ICAM1 mRNA predicted reduced overall survival in SOC. From TCGA and GEO data, SOC patients with ICAM1 mRNA overexpression treated with chemotherapeutic drugs that contained taxol or taxol and platin together had significantly reduced progression-free survival. According to GEO data, ICAM1 mRNA expression was found significantly higher in HGSOC than in control samples. In our study, ICAM-1 overexpression was observed in 63.1% (65/103) of HGSOCs. As a prognostic biomarker, overexpression of ICAM-1 predicted reduced recurrence-free and overall survival and is an independent risk factor for poor prognosis. These findings suggest that overexpression of ICAM-I is an independent indicator of poor prognosis for HGSOC and that it can serve as an effective clinical prognostic biomarker for this disease.

scholarly journals Mechanisms of Chromosomal Instability in High-grade Serous Ovarian Carcinoma

2019 ◽  
Author(s):  
N. Tamura ◽  
N. Shaikh ◽  
D. Muliaditan ◽  
J. McGuinness ◽  
D. Moralli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Single Molecule ◽  
Chromosomal Instability ◽  
Poor Prognosis ◽  
Spindle Assembly Checkpoint ◽  
Western World ◽  
Cancer Type ◽  
High Grade ◽  
Serous Ovarian Carcinoma

AbstractChromosomal instability (CIN), the continual gain and loss of chromosomes or parts of chromosomes, occurs in the majority of cancers and confers poor prognosis. Mechanisms driving CIN remain unknown in most cancer types due to a scarcity of functional studies. High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, is the major cause of death due to gynaecological malignancy in the Western world with chemotherapy resistance developing in almost all patients. HGSC exhibits high rates of chromosome aberrations and knowledge of causative mechanisms is likely to represent an important step towards combating the poor prognosis of this disease. However, very little is known about the nature of chromosomal instability exhibited by this cancer type in particular due to a historical lack of appropriate cell line models. Here we perform the first in-depth functional characterisation of mechanisms driving CIN in HGSC by analysing eight cell lines that accurately recapitulate HGSC genetics as defined by recent studies. We show, using a range of established functional CIN assays combined with live cell imaging and single molecule DNA fibre analysis, that multiple mechanisms co-exist to drive CIN in HGSC. These include supernumerary centrosomes, elevated microtubule dynamics and DNA replication stress. By contrast, the spindle assembly checkpoint was intact. These findings are relevant for developing therapeutic approaches to manipulating CIN in ovarian cancer, and suggests that such approaches may need to be multimodal to combat multiple co-existing CIN drivers.

scholarly journals Low RAP80 mRNA Expression Correlates with Shorter Survival in Sporadic High-Grade Serous Ovarian Carcinoma

2017 ◽  
Vol 32 (1) ◽  
pp. 90-95 ◽  
Author(s):  
Margarita Romeo ◽  
Niki Karachaliou ◽  
Imane Chaid ◽  
Cristina Queralt ◽  
Itziar De Aguirre ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Figo Stage ◽  
High Grade ◽  
Platinum Compounds ◽  
Serous Ovarian Carcinoma ◽  
Platinum Based Chemotherapy

Objective Homologous recombination (HR) is frequently impaired in sporadic high-grade serous ovarian carcinoma (sHGSOC) due to deficiencies in BRCA1/2 genes, a situation associated with hypersensitivity to platinum compounds. Alterations in other genes can also cause HR deficiency. Preclinical data show that RAP80 is an HR–pathway-related gene that influences BRCA1 activity. RAP80 has been reported to affect outcome in some solid neoplasms. This study investigates the role of RAP80 in sHGSOC survival. Methods mRNA expression of RAP80 was analyzed in tumor samples from 35 patients who postoperatively received standard platinum-based chemotherapy. The effects of RAP80 expression on progression-free survival (PFS) and overall survival (OS) were examined by means of Cox regressions. The clinical variables known to have prognostic value (FIGO stage, residual disease at surgery, and debulking surgery) were included as covariates in the analysis. BRCA1 was analyzed given the moderate correlations with RAP80. Results Median follow-up, PFS and OS were 61.3, 20.2 and 62.8 months, respectively. Low RAP80 expression levels were associated with shorter PFS ( HR = 1.449, p = 0.007) and OS ( HR = 1.331, p = 0.047). Conclusions This is the first study to show a potential prognostic role of RAP80 expression in patients with HGSOC. The results suggest that HR deficiency due to low RAP80 expression is not associated with hypersensitivity to platinum compounds in sHGSOC.

scholarly journals MAL gene overexpression as a marker of high-grade serous ovarian carcinoma stem-like cells that predicts chemoresistance and poor prognosis

BMC Cancer ◽  
2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Laura Zanotti ◽  
Chiara Romani ◽  
Laura Tassone ◽  
Paola Todeschini ◽  
Renata Alessandra Tassi ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Poor Prognosis ◽  
Gene Overexpression ◽  
High Grade ◽  
Serous Ovarian Carcinoma

Prognostic impact of HER3 based on protein and mRNA expression in high-grade serous ovarian carcinoma

2016 ◽  
Vol 470 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Ulrike Unger ◽  
Carsten Denkert ◽  
Ioana Braicu ◽  
Jalid Sehouli ◽  
Manfred Dietel ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Prognostic Impact ◽  
High Grade ◽  
Serous Ovarian Carcinoma

scholarly journals USP19 and RPL23 as Candidate Prognostic Markers for Advanced-Stage High-Grade Serous Ovarian Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3976
Author(s):  
Haeyoun Kang ◽  
Min Chul Choi ◽  
Sewha Kim ◽  
Ju-Yeon Jeong ◽  
Ah-Young Kwon ◽  
...  
Keyword(s):  
Machine Learning ◽  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Prognostic Markers ◽  
The Cancer Genome Atlas ◽  
Immune Gene ◽  
Mrna Levels ◽  
High Grade ◽  
Advanced Stage ◽  
Serous Ovarian Carcinoma

Ovarian cancer is one of the leading causes of deaths among patients with gynecological malignancies worldwide. In order to identify prognostic markers for ovarian cancer, we performed RNA-sequencing and analyzed the transcriptome data from 51 patients who received conventional therapies for high-grade serous ovarian carcinoma (HGSC). Patients with early-stage (I or II) HGSC exhibited higher immune gene expression than patients with advanced stage (III or IV) HGSC. In order to predict the prognosis of patients with HGSC, we created machine learning-based models and identified USP19 and RPL23 as candidate prognostic markers. Specifically, patients with lower USP19 mRNA levels and those with higher RPL23 mRNA levels had worse prognoses. This model was then used to analyze the data of patients with HGSC hosted on The Cancer Genome Atlas; this analysis validated the prognostic abilities of these two genes with respect to patient survival. Taken together, the transcriptome profiles of USP19 and RPL23 determined using a machine-learning model could serve as prognostic markers for patients with HGSC receiving conventional therapy.

scholarly journals SERPINE2 Overexpression Is Associated with Poor Prognosis of Urothelial Carcinoma

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1928
Author(s):  
Hao-Wen Chuang ◽  
Kan-Tai Hsia ◽  
Jia-Bin Liao ◽  
Chih-Ching Yeh ◽  
Wei-Ting Kuo ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Urothelial Carcinoma ◽  
Mrna Expression ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Study Data ◽  
The Cancer Genome Atlas ◽  
High Grade ◽  
Pathologic Features

Recent studies have reported that SERPINE2 contributes to the development of various cancers. However, its association with urothelial carcinoma (UC) remains unclear. In this study, data on urinary bladder UC (UBUC) cases from The Cancer Genome Atlas (TCGA) database were used to investigate the prognostic value of SERPINE2 mRNA expression. Then, SERPINE2 expression was analyzed with tissue microarrays constructed from 117 upper tract UC (UTUC) and 84 UBUC tissue specimens using immunohistochemical staining. Results were compared to clinicopathologic data by multivariate analysis. In the TCGA database, high SERPINE2 mRNA expression indicated a poor prognosis in patients with UBUC. Furthermore, Mann–Whitney U test showed that high SERPINE2 immunoexpression was significantly associated with adverse pathologic parameters including invasion, high grade, coexistence of UC in situ, and advanced pT stage (all p < 0.05, except for a marginal association with high-grade UBUC, p = 0.066). Kaplan–Meier analysis revealed that high SERPINE2 expression was associated with worse overall survival (OS; UTUC, p = 0.003; UBUC, p = 0.014) and disease-free survival (UTUC, p = 0.031; UBUC, p = 0.033). Moreover, multivariate analysis identified high SERPINE2 expression as an independent prognostic factor for OS (UTUC, p = 0.002; UBUC, p = 0.024). Taken together, our findings demonstrated that increased SERPINE2 expression is associated with adverse pathologic features and may serve as a prognostic biomarker for UC.

Μελέτη δεικτών μεθυλίωσης στον καρκίνο των ωοθηκών

2019 ◽  
Author(s):  
Λυδία Γιαννοπούλου
Keyword(s):  
Overall Survival ◽  
Ovarian Carcinoma ◽  
Real Time ◽  
Tumor Cells ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
High Grade ◽  
Free Survival ◽  
Serous Ovarian Carcinoma ◽  
Tumor Dna

Ο καρκίνος των ωοθηκών αποτελεί τον τέταρτο συχνότερα εμφανιζόμενο γυναικολογικό καρκίνο και την πέμπτη αιτία θανάτου σχετιζόμενη με καρκίνο στις γυναίκες. Χαρακτηρίζεται από αξιοσημείωτη ιστολογική και μοριακή ετερογένεια, με κυριότερο υπότυπο τον ορώδη καρκίνο ωοθηκών υψηλού βαθμού κακοήθειας (high grade serous ovarian carcinoma, HGSC), που μελετήθηκε στη διατριβή. Η παρούσα διατριβή έχει σκοπό τη μελέτη της μεθυλίωσης επιλεγμένων γονιδίων στον ορώδη καρκίνο ωοθηκών υψηλού βαθμού κακοήθειας. Τα κλινικά δείγματα που χρησιμοποιήθηκαν είναι δείγματα πρωτοπαθών όγκων, αντίστοιχα δείγματα παρακείμενων ιστών, καθώς και αντίστοιχα δείγματα κυκλοφορούντος καρκινικού DNA (circulating tumor DNA, ctDNA) από τις ίδιες ασθενείς. Οι μεθοδολογίες που εφαρμόστηκαν συνιστούν την real-time MSP για την ανίχνευση της μεθυλίωσης σε δείγματα πρωτοπαθών όγκων, παρακείμενων ιστών και πλάσματος, καθώς και την MS-HRMA για τον ημιποσοτικό προσδιορισμό της μεθυλίωσης σε δείγματα πρωτοπαθών όγκων και παρακείμενων ιστών. Αρχικά εξετάστηκε η μεθυλίωση του ογκοκατασταλτικού γονιδίου RASSF1A, όπου πραγματοποιήθηκε μία συγκριτική μελέτη σε δείγματα πρωτοπαθών όγκων, παρακείμενων ιστών και ctDNA ασθενών με HGSC. Η μεθυλίωση του γονιδίου στα δείγματα πρωτοπαθών όγκων και παρακείμενων ιστών συσχετίστηκε με σημαντικά μειωμένη ολική επιβίωση (overall survival, OS) των ασθενών. Τα συνολικά αποτελέσματα της μελέτης υπέδειξαν για πρώτη φορά την προγνωστική σημασία της μεθυλίωσης του γονιδίου στον HGSC. Στη συνέχεια, ακολούθησε μελέτη μεθυλίωσης του γονιδίου ESR1, όπου πραγματοποιήθηκε μελέτη σε δείγματα πρωτοπαθών όγκων και ctDNA ασθενών με HGSC. Η μεθυλίωση του γονιδίου στα δείγματα πρωτοπαθών όγκων συσχετίστηκε με σημαντικά αυξημένα OS και διάστημα επιβίωσης χωρίς εξέλιξη της νόσου (progression free survival, PFS) των ασθενών. H παρούσα μελέτη αποτέλεσε μία προσπάθεια αποσαφήνισης του ρόλου της μεθυλίωσης του γονιδίου στον HGSC. Ακολούθησαν οι μελέτες μεθυλίωσης γονιδίων που εμπλέκονται σε μοριακά μονοπάτια που διαταράσσονται στον HGSC, όπως τα γονίδια BRCA1 και MGMT που συμμετέχουν σε διαφορετικές πορείες επιδιόρθωσης του DNA, το γονίδιο NR2F1 που συμμετέχει ενεργά στην κυτταρική αδράνεια, τα γονίδιο RASSF10 που εμπλέκεται στην ανάπτυξη χημειοαντίστασης, καθώς και το γονίδιο RKIP που συμμετέχει στην ΕΜΤ διαδικασία. Ύστερα από τη συνολική επεξεργασία των αποτελεσμάτων, παρατηρήθηκε στατιστικά σημαντική συσχέτιση της μεθυλίωσης του γονιδίου NR2F1 στα δείγματα πρωτοπαθών όγκων, με μειωμένο PFS. Επιπλέον, η μεθυλίωση του γονιδίου BRCA1 στο ctDNA συσχετίστηκε με σημαντικά αυξημένο PFS. Τέλος, πραγματοποιήθηκε μελέτη της έκφρασης του γονιδίου PD-L1 σε δείγματα κυκλοφορούντων καρκινικών κυττάρων (circulating tumor cells, CTCs) ασθενών με HGSC, με την εφαρμογή RT-qPCR. Με βάση τα αποτελέσματα της μελέτης, παρατηρήθηκε στατιστικά σημαντική συσχέτιση της έκφρασης του γονιδίου με μειωμένη OS των ασθενών, υποδεικνύοντας μία πιθανή προγνωστική σημασία στον HGSC.

scholarly journals Most commonly mutated genes in High Grade Serous Ovarian Carcinoma are nonessential for ovarian surface epithelial stem cell transformation

2020 ◽  
Author(s):  
Robert J. Yamulla ◽  
Shreya Nalubola ◽  
Andrea Flesken-Nikitin ◽  
Alexander Yu. Nikitin ◽  
John C. Schimenti
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ovarian Carcinoma ◽  
Gynecological Cancer ◽  
The Cancer Genome Atlas ◽  
Research Network ◽  
Surface Epithelium ◽  
High Grade ◽  
Ovarian Surface ◽  
Serous Ovarian Carcinoma

AbstractHigh grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological cancer and the 5th leading cause of cancer-related deaths of women in the USA. Disease-associated mutations have been identified by the Cancer Genome Atlas Research Network. However, aside from mutations in TP53 or alterations in the RB1 pathway that are extremely common in HGSOC, the contributions of other mutation combinations have been difficult to assess experimentally or with genomic data alone. Previous research identified ALDH+ stem cells of the ovarian surface epithelium (OSE) as one of the putative cells of HGSOC origin. Here, we performed combinatorial CRISPR mutagenesis of 20 putative HGSOC driver genes to identify mutation combinations that transformed OSE stem cells (OSE-SC) and non-stem cells (OSE-NS). Overrepresented mutations and mutation combinations were identified in all transformants and were investigated directly in targeted assays. Our results support the OSE stem cell theory of HGSOC initiation and suggest that most commonly mutated genes in HGSOC have no effect on OSE-SC transformation initiation. We suggest a model in which combined disruption of RB1 and PTEN, in addition to TP53 deficiency, constitutes a core set of mutations required for efficient transformation in vitro. A few previously uncharacterized mutation combinations further enhanced transformation but may have done so via TP53-related mechanisms. Together, our results identify mutation combinations that are critical for OSE-SC transformation and may contribute to more accurate modeling of HGSOC development. Our cancer driver screening methodology may also serve as a model for high throughput functional assessment of commonly mutated genes uncovered in other cancers by large scale sequencing.

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