scholarly journals Transcriptome-based Stemness Indices Analysis Reveals Platinum-based Chemotheraputic Response Indicators in Advanced-stage Serous Ovarian Cancer

2020 ◽  
Author(s):  
Xinwei Sun ◽  
Qingyu Liu ◽  
Jie Huang ◽  
Ge Diao ◽  
Zhiqing Liang
Keyword(s):  
Ovarian Cancer ◽  
Progression Free Survival ◽  
Gene Expression Omnibus ◽  
Mitotic Division ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Differentiation Potential ◽  
Key Genes ◽  
Grade 3 ◽  
Response Indicators

Abstract Background: Serous ovarian cancer (SOC) is a main histological subtype of ovarian cancer (OC). Cancer stem cells (CSCs), with self-renewal and differentiation potential, are considered to be the cause of chemoresistance in SOC. However, the underlying modulation mechanisms of chemoresistance led by cancer stemness are still undefined. Results: We found that mRNAsi and corrected mRNAsi (by tumor purity) scores were both greater in tumors of Grade 3 and 4 than that of Grade 1 and 2, indicating a stronger stemness in cancer cells of higher grades. A total of 42 key genes were obtained from the most significant mRNAsi-related gene module. Functional annotation revealed that these key genes were mainly involved in mitotic division and were closely related to cell proliferation. A total of 13 potential platinum response indicators were selected from the genes enriched to platinum-response associated pathways. Among the 13 key genes, we identified 11 genes with prognostic value of progression-free survival (PFS) in advanced-stage SOC patients treated with chemotherapy containing platinum and 7 prognostic genes in patients treated with the combination of platinum and taxol. The expression of the 13 key genes was also validated between platinum-resistant and sensitive SOC samples of advanced stages in two Gene Expression Omnibus (GEO) datasets. Conclusion: The results revealed that CDC20 was a potential platinum-based chemotherapeutic response indicator in advanced-stage SOC and the findings may provide new insight into the prediction of drug response thus to guiding the use of chemotherapies in patients of advanced-stage SOC in the clinic.

scholarly journals Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

2016 ◽  
Vol 397 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Nancy Ahmed ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Enken Drecoll ◽  
Matthias Kotzsch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Residual Tumor ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

scholarly journals High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Min Li ◽  
Xue Cheng ◽  
Rong Rong ◽  
Yan Gao ◽  
Xiuwu Tang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Paraffin Section ◽  
Progression Free Survival ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Systematic Analysis ◽  
Cox Regression Analysis ◽  
Genes Expression ◽  
High Level

Abstract Background High-grade serous ovarian cancer (HGSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HGSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HGSOC. Methods TCGA database was conducted to analyze relevant genes expression in HGSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HGSOC patients to validate gene expression in different stages of HGSOC. Results Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HGSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HGSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HGSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HGSOC survival. Conclusions High-level expression of FAP was associated with poor prognosis of HGSOC via FN1 pathway.

scholarly journals SOX2 is a promising predictor of relapse and death in advanced stage high-grade serous ovarian cancer patients with residual disease after debulking surgery

2020 ◽  
Vol 7 (6) ◽  
pp. 1805094
Author(s):  
Maria Bååth ◽  
Sofia Westbom-Fremer ◽  
Laura Martin de la Fuente ◽  
Anna Ebbesson ◽  
Juliette Davis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Residual Disease ◽  
High Grade ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Debulking Surgery

Abstract 1507: TGF-beta induced stromal versican promotes cancer invasion in advanced stage serous ovarian cancer

2012 ◽  
Author(s):  
Tsz-Lun Yeung ◽  
Cecilia Leung ◽  
Sue Ghosh ◽  
Jinsong Liu ◽  
Kwong-Kwok Wong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Invasion ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Tgf Beta

scholarly journals Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan

2013 ◽  
Vol 52 (1) ◽  
pp. 81-84 ◽  
Author(s):  
Kuan-Chong Chao ◽  
Yi-Jen Chen ◽  
Chi-Mou Juang ◽  
Hei-Yu Lau ◽  
Kuo-Chang Wen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Papillary Carcinoma ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Serous Papillary Carcinoma

scholarly journals Molecular Profiling and Clinical Outcome of High-Grade Serous Ovarian Cancer Presenting with Low- versus High-Volume Ascites

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Tomer Feigenberg ◽  
Blaise Clarke ◽  
Carl Virtanen ◽  
Anna Plotkin ◽  
Michelle Letarte ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Clinical Outcome ◽  
Expression Profiles ◽  
High Volume ◽  
High Grade ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Immune Response Genes ◽  
Low Volume

Epithelial ovarian cancer consists of multiple histotypes differing in etiology and clinical course. The most prevalent histotype is high-grade serous ovarian cancer (HGSOC), which often presents at an advanced stage frequently accompanied with high-volume ascites. While some studies suggest that ascites is associated with poor clinical outcome, most reports have not differentiated between histological subtypes or tumor grade. We compared genome-wide gene expression profiles from a discovery cohort of ten patients diagnosed with stages III-IV HGSOC with high-volume ascites and nine patients with low-volume ascites. An upregulation of immune response genes was detected in tumors from patients presenting with low-volume ascites relative to those with high-volume ascites. Immunohistochemical studies performed on tissue microarrays confirmed higher expression of proteins encoded by immune response genes and increased tumorinfiltrating cells in tumors associated with low-volume ascites. Comparison of 149 advanced-stage HGSOC cases with differential ascites volume at time of primary surgery indicated low-volume ascites correlated with better surgical outcome and longer overall survival. These findings suggest that advanced stage HGSOC presenting with low-volume ascites reflects a unique subgroup of HGSOC, which is associated with upregulation of immune related genes, more abundant tumor infiltrating cells and better clinical outcomes.

scholarly journals Identification of FGFR4 as a Potential Therapeutic Target for Advanced-Stage, High-Grade Serous Ovarian Cancer

2013 ◽  
Vol 19 (4) ◽  
pp. 809-820 ◽  
Author(s):  
Tarrik M. Zaid ◽  
Tsz-Lun Yeung ◽  
Melissa S. Thompson ◽  
Cecilia S. Leung ◽  
Tom Harding ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Therapeutic Target ◽  
High Grade ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Potential Therapeutic Target
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