scholarly journals Distinct gene expression profiles associated with clinical outcomes in patients with ovarian clear cell carcinoma and high-grade serous ovarian carcinoma

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Huimei Zhou ◽  
Qian Liu ◽  
Xiaohua Shi ◽  
Yue Liu ◽  
Dongyan Cao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Carcinoma ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
High Grade ◽  
Ovarian Clear Cell Carcinoma ◽  
Serous Ovarian Carcinoma

scholarly journals The Potential Role of Complement System in the Progression of Ovarian Clear Cell Carcinoma Inferred from the Gene Ontology-Based Immunofunctionome Analysis

2020 ◽  
Vol 21 (8) ◽  
pp. 2824 ◽  
Author(s):  
Kuo-Min Su ◽  
Tzu-Wei Lin ◽  
Li-Chun Liu ◽  
Yi-Pin Yang ◽  
Mong-Lien Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Cell Carcinoma ◽  
Complement System ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Expression Profiles ◽  
Alternative Pathway ◽  
Ovarian Clear Cell Carcinoma ◽  
C5a Receptor

Ovarian clear cell carcinoma (OCCC) is the second most common epithelial ovarian carcinoma (EOC). It is refractory to chemotherapy with a worse prognosis after the preliminary optimal debulking operation, such that the treatment of OCCC remains a challenge. OCCC is believed to evolve from endometriosis, a chronic immune/inflammation-related disease, so that immunotherapy may be a potential alternative treatment. Here, gene set-based analysis was used to investigate the immunofunctionomes of OCCC in early and advanced stages. Quantified biological functions defined by 5917 Gene Ontology (GO) terms downloaded from the Gene Expression Omnibus (GEO) database were used. DNA microarray gene expression profiles were used to convert 85 OCCCs and 136 normal controls into to the functionome. Relevant offspring were as extracted and the immunofunctionomes were rebuilt at different stages by machine learning. Several dysregulated pathogenic functions were found to coexist in the immunopathogenesis of early and advanced OCCC, wherein the complement-activation-alternative-pathway may be the headmost dysfunctional immunological pathway in duality for carcinogenesis at all OCCC stages. Several immunological genes involved in the complement system had dual influences on patients’ survival, and immunohistochemistrical analysis implied the higher expression of C3a receptor (C3aR) and C5a receptor (C5aR) levels in OCCC than in controls.

Integrative genomic and transcriptomic analysis reveals prognostic markers and immune subtype in Chinese ovarian clear cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17529-e17529
Author(s):  
Huijuan Yang ◽  
Shuang Ye ◽  
Qin Li ◽  
Yutuan Wu ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Carcinoma ◽  
Prognostic Markers ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Genetic Alterations ◽  
Transcriptomic Analysis ◽  
Clinical Factors ◽  
Ovarian Clear Cell Carcinoma ◽  
Poor Survival

e17529 Background: Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer characterized by chemo-resistance and poor survival. Herein, we performed comprehensive genomic and transcriptomic profiling of OCCC tissues to identify prognostic markers and immune subtype in Chinese patients. Methods: A total of 61 patients were included, comprising 41 early-stage and 19 late-stage tumors. Tissue samples were collected before chemotherapy and subjected to capture-based targeted sequencing using a panel consisting of 520 cancer related genes and whole transcriptomic sequencing. Genetic alterations, tumor mutation burden (TMB), microsatellite instability (MSI), and gene expression were evaluated. Association analysis was performed to evaluate clinical and genetic factors with platinum-sensitivity and treatment effects. A nomogram was constructed to predict survival outcomes. Single sample Gene Set Enrichment analysis (ssGSEA) was performed with gene expression profile and immune gene sets. Results: Genetic alterations were mainly identified in ARID1A (49%), PIK3CA (48%), TP53 (18%), ATM (15%), SMARCA4 (13%) and PRKDC (13%). Co-occurrence of mutations in ARID1A with PIK3CA and PRKDC were observed (p < 0.05). Meanwhile, no alterations were identified in BRCA1/2. Patients harboring ATM mutations tended to be platinum sensitive compared to those wildtype counterparts (p < 0.05). In patients with stage IV OCCC, mutations of ARID1A, PIK3CA, SMARCA4 and the HRR pathway were also related to higher percentage of platinum-sensitivity, though significance was not achieved. Mutations of FGFR2, NOTCH1 and the BER pathway were more frequently identified in patients with stage II to IV than stage I (p < 0.05). Patients harboring alterations at chromosome 8q covering genes such as PRKDC showed better overall survival (OS) (p < 0.05). Both clinical factors and frequently mutated genes were used to construct a nomogram for progression-free survival (PFS) prediction. The clinical factors (stage, platinum response and residual disease) in combination with genetic mutations ( ATM and SMARCA4) showed better performance in predicting PFS than clinical factors alone (concordance index 0.85 vs. 0.74, p < 0.01). Transcriptomic analysis with ssGSEA of immune pathway revealed an immune subtype with enrichment of PD-1 signaling. OCCC patients with this immune subtype showed poor PFS and OS. Integration of genomic and transcriptomic analysis showed that the immune subtype patients had higher mutation rate of PIK3CA. Conclusions: The mutational profiles of OCCC were varied in patients with different platinum response and tumor stages. An immune subtype of OCCC with poor survival and enrichment of PD-1 signaling was identified. Our study identified several potential prognostic markers of OCCC at genetic level and revealed an immune subtype for potential immunotherapy.

scholarly journals Cytokine gene expression signature in ovarian clear cell carcinoma

2012 ◽  
Vol 41 (3) ◽  
pp. 1094-1100 ◽  
Author(s):  
NOZOMU YANAIHARA ◽  
MICHAEL S. ANGLESIO ◽  
KAZUNORI OCHIAI ◽  
YUKIHIRO HIRATA ◽  
MISATO SAITO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Gene Expression Signature ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Ovarian Clear Cell Carcinoma ◽  
Expression Signature

scholarly journals MicroRNA Gene Expression Signature Driven by miR-9 Overexpression in Ovarian Clear Cell Carcinoma

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162584 ◽  
Author(s):  
Nozomu Yanaihara ◽  
Yukiko Noguchi ◽  
Misato Saito ◽  
Masataka Takenaka ◽  
Satoshi Takakura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Gene Expression Signature ◽  
Ovarian Clear Cell Carcinoma ◽  
Expression Signature ◽  
Microrna Gene

The Analysis of Cell Cycle–related Proteins in Ovarian Clear Cell Carcinoma Versus High-grade Serous Carcinoma

2018 ◽  
Vol 37 (6) ◽  
pp. 516-524 ◽  
Author(s):  
Yukiko Hazama ◽  
Takuya Moriya ◽  
Mika Sugihara ◽  
Rikiya Sano ◽  
Mitsuru Shiota ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Serous Carcinoma ◽  
High Grade ◽  
Ovarian Clear Cell Carcinoma ◽  
Related Proteins

scholarly journals Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3854
Author(s):  
Saira Khalique ◽  
Sarah Nash ◽  
David Mansfield ◽  
Julian Wampfler ◽  
Ayoma Attygale ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Spatial Distribution ◽  
Cell Carcinoma ◽  
Immune Cell ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Cell Populations ◽  
Ovarian Clear Cell Carcinoma ◽  
Risk Patients

Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by a high frequency of loss-of-function ARID1A mutations and a poor response to chemotherapy. Despite their generally low mutational burden, an intratumoural T cell response has been reported in a subset of OCCC, with ARID1A purported to be a biomarker for the response to the immune checkpoint blockade independent of micro-satellite instability (MSI). However, assessment of the different immune cell types and spatial distribution specifically within OCCC patients has not been described to date. Here, we characterised the immune landscape of OCCC by profiling a cohort of 33 microsatellite stable OCCCs at the genomic, gene expression and histological level using targeted sequencing, gene expression profiling using the NanoString targeted immune panel, and multiplex immunofluorescence to assess the spatial distribution and abundance of immune cell populations at the protein level. Analysis of these tumours and subsequent independent validation identified an immune-related gene expression signature associated with risk of recurrence of OCCC. Whilst histological quantification of tumour-infiltrating lymphocytes (TIL, Salgado scoring) showed no association with the risk of recurrence or ARID1A mutational status, the characterisation of TILs via multiplexed immunofluorescence identified spatial differences in immunosuppressive cell populations in OCCC. Tumour-associated macrophages (TAM) and regulatory T cells were excluded from the vicinity of tumour cells in low-risk patients, suggesting that high-risk patients have a more immunosuppressive microenvironment. We also found that TAMs and cytotoxic T cells were also excluded from the vicinity of tumour cells in ARID1A-mutated OCCCs compared to ARID1A wild-type tumours, suggesting that the exclusion of these immune effectors could determine the host response of ARID1A-mutant OCCCs to therapy. Overall, our study has provided new insights into the immune landscape and prognostic associations in OCCC and suggest that tailored immunotherapeutic approaches may be warranted for different subgroups of OCCC patients.

scholarly journals Comparison of the Clinical Characteristics and Prognosis Between Clear Cell Carcinomas and High-grade Serous Ovarian Carcinomas

2021 ◽  
Author(s):  
Shixiang Dong ◽  
Fengsheng Yu ◽  
Yutong Liu ◽  
Xiao Yu ◽  
Xin Sun ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Figo Stage ◽  
R0 Resection ◽  
High Grade ◽  
Ovarian Clear Cell Carcinoma ◽  
Factors Affecting ◽  
Serous Ovarian Carcinoma ◽  
Independent Risk Factors

Abstract Objectives: To compare the clinical characteristics and prognosis of women with clear cell versus high-grade serous ovarian carcinoma.Methods: Retrospective analysis of the clinical data of 50 cases patients with ovarian clear cell carcinoma (OCCC) and 103 cases with high-grade serous ovarian carcinoma (HGSOC), who were initially treated and completed standardized therapy in Affiliated Hospital of Qingdao University from January 2013 to December 2017.Results: There were significant differences in age, gravidity (G > 1), chief complaint, with ovarian endometriosis, tumor diameter, unilateral or bilateral, cystic and solid tumor, CA125, HE4, CA199, lactate dehydrogenase (LDH), and FIGO stage between the two groups. The differences in the prognosis between OCCC patients and HGSOC patients with early stage (FIGO I-II) were not statistically significant. The 5-year overall survival and progression-free survival of OCCC patients were significantly worse than those of HGSOC patients with advanced stage (FIGO III-IV) (P < 0.05). FIGO stage and non-R0 resection were independent risk factors affecting the prognosis of patients with ovarian clear cell carcinoma, screening by Cox regression analysis. FIGO stage, the lowest value of CA125, and non-R0 resection were independent risk factors affecting the prognosis of patients with high-grade serous ovarian cancer.Conclusions: The clinical characteristics and prognosis of OCCC are different from those of HGSOC. OCCC patients have a significantly worse prognosis than those with HGSOC in the advanced stage (FIGO Ⅲ-Ⅳ). Satisfactory tumor resection is an essential factor related to the prognosis of patients with OCCC and HGSOC.

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