scholarly journals Mining of Subtype Markers for the Prognosis of Ovarian Cancer based on Methylation Data

2020 ◽  
Author(s):  
Lili Yin ◽  
Ningning Zhang ◽  
Qing Yang

Abstract Background: Ovarian cancer is one of three major malignancies involving the female reproductive system, and its morbidity and mortality are ranked number 3 and number 1 among gynecological tumors, respectively. DNA methylation (MET), as one of the main epigenetic modes, is closely related to the occurrence and development of ovarian cancer. To guide individualized treatment and improve the prognosis in ovarian cancer patients, it is of great significance to elucidate effective MET subtype markers.Methods: A total of 571 ovarian cancer MET samples were downloaded from the Cancer Genome Atlas (TCGA), and a COX proportional hazards model was established using the MET spectrum and clinically pathological parameters. Subsequently, the consensus clustering of CpG loci with a significant difference in both univariate and multivariate analyses was performed to screen the molecular subtypes, and these CpG loci were subjected to gene function annotation. Finally, CpG MET loci associated with poor prognosis in ovarian cancer patients were further screened by constructing a weighted gene co-expression network analysis (WGCNA).Results: A total of 250 prognosis-related MET loci were obtained by COX regression and 6 molecular subtypes were screened by clustering. There was a remarkable MET difference between most subtypes, of which Cluster 2 had the highest MET level and demonstrated the best prognosis in patients, while Cluster 4 and Cluster 5 had a MET level significantly lower than that of the other subtypes and demonstrated a very poor prognosis. All Cluster 5 samples were at a high grade, while the percentage of Stage IV samples in Cluster 4 was evidently greater than that in the other subtypes. Using the co-expression network, 5 CpG loci were eventually obtained: cg27625732, cg00431050, cg22197830, cg03152385, and cg22809047. The clustering analysis shows that the prognosis in patients with hypomethylation was significantly worse than that in patients with hypermethylation. Conclusions: These MET molecular subtypes can be used not only to evaluate the prognosis in ovarian cancer patients but also to fully distinguish the tumor stage and histological grade in these patients. Prognosis-related CpG loci can be applied as biomarkers for individualized treatment in ovarian cancer patients.

2020 ◽  
Author(s):  
Lili Yin ◽  
Ningning Zhang ◽  
Qing Yang

Abstract Aims: Ovarian cancer is one of three major malignancies involving the female reproductive system, and its morbidity and mortality are ranked number 3 and number 1 among gynecological tumors, respectively. DNA methylation (MET), as one of the main epigenetic modes, is closely related to the occurrence and development of ovarian cancer. To guide individualized treatment and improve the prognosis in ovarian cancer patients, it is of great significance to elucidate effective MET subtype markers. Methods: A total of 571 ovarian cancer MET samples were downloaded from the Cancer Genome Atlas (TCGA), and a COX proportional hazards model was established using the MET spectrum and clinically pathological parameters. Subsequently, the consensus clustering of CpG loci with a significant difference in both univariate and multivariate analyses was performed to screen the molecular subtypes, and these CpG loci were subjected to gene function annotation. Finally, CpG MET loci associated with poor prognosis in ovarian cancer patients were further screened by constructing a weighted gene co-expression network analysis (WGCNA). Results: A total of 250 prognosis-related MET loci were obtained by COX regression and 6 molecular subtypes were screened by clustering. There was a remarkable MET difference between most subtypes, of which Cluster 2 had the highest MET level and demonstrated the best prognosis in patients, while Cluster 4 and Cluster 5 had a MET level significantly lower than that of the other subtypes and demonstrated a very poor prognosis. All Cluster 5 samples were at a high grade, while the percentage of Stage IV samples in Cluster 4 was evidently greater than that in the other subtypes. Using the co-expression network, 5 CpG loci were eventually obtained: cg27625732, cg00431050, cg22197830, cg03152385, and cg22809047. The clustering analysis shows that the prognosis in patients with hypomethylation was significantly worse than that in patients with hypermethylation. Conclusions: These MET molecular subtypes can be used not only to evaluate the prognosis in ovarian cancer patients but also to fully distinguish the tumor stage and histological grade in these patients. Prognosis-related CpG loci can be applied as biomarkers for individualized treatment in ovarian cancer patients.


2020 ◽  
Author(s):  
Lili Yin ◽  
Ningning Zhang ◽  
qing yang

Abstract Aims: Ovarian cancer is one of three major malignancies involving the female reproductive system, and its morbidity and mortality are ranked number 3 and number 1 among gynecological tumors, respectively. DNA methylation (MET), as one of the main epigenetic modes, is closely related to the occurrence and development of ovarian cancer. To guide individualized treatment and improve the prognosis in ovarian cancer patients, it is of great significance to elucidate effective MET subtype markers. Methods: A total of 571 ovarian cancer MET samples were downloaded from the Cancer Genome Atlas (TCGA), and a COX proportional hazards model was established using the MET spectrum and clinically pathological parameters. Subsequently, the consensus clustering of CpG loci with a significant difference in both univariate and multivariate analyses was performed to screen the molecular subtypes, and these CpG loci were subjected to gene function annotation. Finally, CpG MET loci associated with poor prognosis in ovarian cancer patients were further screened by constructing a weighted gene co-expression network analysis (WGCNA). Results: A total of 250 prognosis-related MET loci were obtained by COX regression and 6 molecular subtypes were screened by clustering. There was a remarkable MET difference between most subtypes, of which Cluster 2 had the highest MET level and demonstrated the best prognosis in patients, while Cluster 4 and Cluster 5 had a MET level significantly lower than that of the other subtypes and demonstrated a very poor prognosis. All Cluster 5 samples were at a high grade, while the percentage of Stage IV samples in Cluster 4 was evidently greater than that in the other subtypes. Using the co-expression network, 5 CpG loci were eventually obtained: cg27625732, cg00431050, cg22197830, cg03152385, and cg22809047. The clustering analysis shows that the prognosis in patients with hypomethylation was significantly worse than that in patients with hypermethylation. Conclusions: These MET molecular subtypes can be used not only to evaluate the prognosis in ovarian cancer patients but also to fully distinguish the tumor stage and histological grade in these patients. Prognosis-related CpG loci can be applied as biomarkers for individualized treatment in ovarian cancer patients.


2020 ◽  
Author(s):  
Chenyan Fang ◽  
Yingli Zhang ◽  
Lingqin Zhao ◽  
Xi Chen ◽  
Liang Xia ◽  
...  

Abstract Background Systematic retroperitoneal lymphadenectomy has been widely used in the surgical treatment of advanced ovarian cancer patients. Nevertheless, the corresponding therapeutic may not provide a survival benefit. The aim of this study was to assess the effect of systematic retroperitoneal lymphadenectomy in such patients. Methods Patients with advanced ovarian cancer (stage III-IV, according to the classification presented by the International Federation of Gynecology and Obstetrics) who were admitted and treated in Zhejiang Cancer Hospital from January 2004 to December 2013 were enrolled and reviewed retrospectively. All patients were optimally or suboptimally debulked (absent or residual tumor <1 cm) and divided into two groups. Group A (no-lymphadenectomy group, n =170): patients did not undergo lymph node resection; lymph nodes resection or biopsy were selective. Group B (n=240): patients underwent systematic retroperitoneal lymphadenectomy. Results A total of 410 eligible patients were enrolled in the study. The patients’ median age was 51 years old (range, 28–72 years old). The 5-year overall survival (OS) and 2-year progression-free survival (PFS) rates were 78% and 24% in the no-lymphadenectomy group and 76% and 26% in the lymphadenectomy group (P=0.385 and 0.214, respectively). Subsequently, there was no significant difference in 5-year OS and 2-year PFS between the two groups stratified to histological types (serous type or non-serous type), the clinical evaluation of negative lymph nodes or with macroscopic peritoneal metastasis beyond pelvic (IIIB-IV). Multivariate Cox regression analysis indicated that systematic retroperitoneal lymphadenectomy was not a significant factor influencing the patients’ survival. Patients in the lymphadenectomy group had a higher incidence of postoperative complications (incidence of infection treated with antibiotics was 21.7% vs. 12.9% [P=0.027]; incidence of lymph cysts was 20.8% vs. 2.4% [P < 0.001]). Conclusions Our study showed that systematic retroperitoneal lymphadenectomy did not significantly improve survival of advanced ovarian cancer patients with residual tumor <1 cm or absent after cytoreductive surgery, and were associated with a higher incidence of postoperative complications.


2020 ◽  
Author(s):  
Nan Zhang ◽  
Zhiyou Yang ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Jiani Yang ◽  
...  

Abstract Background Ovarian cancer remains one of the most lethal malignancies in women which is typically diagnosed at a late stage and has no effective screening strategy. It is essential to explore novel biomarkers for the diagnosis and prognosis of ovarian cancer, as well as therapeutic targets. Recent studies have shown that circRNAs participate in ovarian cancer progression by regulating various processes and being able to act as potential biomarkers for ovarian cancer diagnosis and prognosis. In the present study we aimed to explore the prognostic role of circ_0078607 in high-grade serous ovarian cancer. Results The expression of circ_0078607 in 49 high-grade serous ovarian cancer and adjacent non-cancerous tissue samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). We noticed that circ_0078607 expression was significantly downregulated in ovarian cancer tissues compared with adjacent non-cancerous tissues. Besides, patients with low circ_0078607 expression exhibited parameters associated with poor prognosis, including advanced FIGO stage and higher serum CA125 level. Kaplan-Meier survival curve analysis showed that both progression-free survival and overall survival were significantly shortened in patients with low circ_0078607 expression. Cox regression model analysis showed that low expression of circ_0078607 was an adverse prognostic indicator for high-grade serous ovarian cancer patients. Conclusions Low expression of circ_0078607 might be an adverse prognostic indicator for high-grade serous ovarian cancer patients.


2020 ◽  
Author(s):  
Chenyan Fang ◽  
Yingli Zhang ◽  
Lingqin Zhao ◽  
Xi Chen ◽  
Liang Xia ◽  
...  

Abstract Background Systematic retroperitoneal lymphadenectomy has been widely used in the surgical treatment of advanced ovarian cancer patients. Nevertheless, the corresponding therapeutic may not provide a survival benefit. The aim of this study was to assess the effect of systematic retroperitoneal lymphadenectomy in such patients. Methods Patients with advanced ovarian cancer (stage III-IV, according to the classification presented by the International Federation of Gynecology and Obstetrics) who were admitted and treated in Zhejiang Cancer Hospital from January 2004 to December 2013 were enrolled and reviewed retrospectively. All patients were optimally or suboptimally debulked (absent or residual tumor <1 cm) and divided into two groups. Group A (no-lymphadenectomy group, n =170): patients did not undergo lymph node resection; lymph nodes resection or biopsy were selective. Group B (n=240): patients underwent systematic retroperitoneal lymphadenectomy. Results A total of 410 eligible patients were enrolled in the study. The patients’ median age was 51 years old (range, 28–72 years old). The 5-year overall survival (OS) and 2-year progression-free survival (PFS) rates were 78% and 24% in the no-lymphadenectomy group and 76% and 26% in the lymphadenectomy group (P=0.385 and 0.214, respectively). Subsequently, there was no significant difference in 5-year OS and 2-year PFS between the two groups stratified to histological types (serous type or non-serous type), the clinical evaluation of negative lymph nodes or with macroscopic peritoneal metastasis beyond pelvic (IIIB-IV). Multivariate Cox regression analysis indicated that systematic retroperitoneal lymphadenectomy was not a significant factor influencing the patients’ survival. Patients in the lymphadenectomy group had a higher incidence of postoperative complications (incidence of infection treated with antibiotics was 21.7% vs. 12.9% [P=0.027]; incidence of lymph cysts was 20.8% vs. 2.4% [P < 0.001]). Conclusions Our study showed that systematic retroperitoneal lymphadenectomy did not significantly improve survival in advanced ovarian cancer patients with residual tumor <1 cm or absent after cytoreductive surgery, and were associated with a higher incidence of postoperative complications.


2020 ◽  
Author(s):  
Yuexin Hu ◽  
Mingjun Zheng ◽  
Caixia Wang ◽  
Shuang Wang ◽  
Rui Gou ◽  
...  

Abstract Background: Ovarian cancer is one of the common malignant tumors in gynecology. Although the treatment strategy for ovarian cancer has been greatly improved in recent years, due to the metastasis, recurrence and drug resistance, the 5-year overall survival rate of patients is still less than 47%. However, at present, there is no specific markers for clinical application. The purpose of this study is to verify the expression and clinical significance of KIF23 in ovarian cancer and identify potential targets for the clinical treatment of ovarian cancer. Methods: The expression of KIF23 in ovarian cancer tissues and its relationship between survival prognosis and clinical pathological parameters were analyzed in Oncomine, GEO, and TCGA databases. KIF23 expression was analyzed by Kaplan-Meier plotter database and its relationship with chemo-resistance was studied. The molecular mechanism involved in KIF23 was analyzed from the perspective of gene mutation, copy number variation and other genomics. Finally, immunohistochemistry experiment was used to verify the expression of KIF2, and its relationship between the clinical pathological parameters and prognosis of ovarian cancer patients was analyzed by single factor and multivariate Cox regression models. Results: Bioinformatic and experimental results have demonstrated that KIF23 is highly expressed in ovarian cancer, and its high expression is positively correlated with poor prognosis. Overexpression of KIF23 can cause chemotherapy resistance in ovarian cancer and affect the overall survival of patients. Genomics analysis showed that KIF23 expression was associated with mutations such as FLG2 and TTN, and it was significantly enriched in tumor signaling pathways such as DNA replication and cell cycle. Conclusions: KIF23 can not only be used as a biomarker of poor prognosis in patients with various stages of ovarian cancer, but also be used as a molecular targeted drug and an independent prognostic biomarker for the treatment of ovarian cancer patients.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18720-e18720
Author(s):  
Christine G. Kohn ◽  
Jonathan T. Caranfa ◽  
Molly Brewer ◽  
Meghana Singh ◽  
Craig I. Coleman ◽  
...  

e18720 Background: There is a paucity of real-world data regarding rates of recurrent venous thromboembolism (VTE), major bleeding and all-cause mortality among ovarian cancer patients with thrombosis treated with direct oral anticoagulants (DOACs) currently available. We sought to evaluate the effectiveness and safety of rivaroxaban versus low molecular-weight heparin (LMWH) for cancer-associated thrombosis (CAT) treatment in patients with ovarian cancer. Methods: We utilized US Surveillance, Epidemiology and End Results-Medicare–linked data from 2013-2016 to identify adults with active ovarian cancer, undergoing hospitalization/emergency department admission for CAT and prescribed rivaroxaban or LMWH for outpatient anticoagulation. Rivaroxaban and LMWH cohorts were balanced using propensity score overlap weighting . Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately and mortality at six-months using an intention-to-treat approach. On-treatment analysis after 12-months was also performed. Hazard ratios (HRs) with 95% confidence intervals using overlap weighted cox regression were reported. Results: We included 33 rivaroxaban and 92 LMWH-managed CAT patients. In each cohort, mean age was 73, 79.5% of patients were white, 46.9% had a history of ≥ stage 3 chronic kidney disease (CKD), two-thirds had metastatic disease at the time of VTE, and 32.6% had a prior VTE. Patients were diagnosed with ovarian cancer an average of 1.40 years prior to the index VTE event and 45.8% had a pulmonary embolism (with or without DVT) as the index event. Our analysis did not detect a significant difference in outcomes with rivaroxaban versus LMWH at six-months (Table). On-treatment analysis at 12-months showed similar results. Conclusions: Rivaroxaban may be a reasonable alternative to LMWH for CAT patients with ovarian cancer. Large observational studies are needed to confirm these results.[Table: see text]


2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Juan Liu ◽  
Zongjian Tan ◽  
Jun He ◽  
Tingting Jin ◽  
Yuanyuan Han ◽  
...  

Abstract Background: Increasing studies suggest that tumor immune infiltration is a relative factor of prognosis in ovarian cancer (OvCa). The present study explored the composition of tumor-infiltrating immune cells (TIICs) in OvCa using CIBERSORT algorithm and further assessed their values for prognosis and therapeutic strategies by molecular subtypes. Methods: Publicly available databases including The Cancer Genome Atlas (TCGA) and GTEx were searched. Ovarian tumor samples were available from TCGA, and normal ovarian samples were obtained from the GTEx dataset. The relative proportions of immune cell profiling in OvCa and normal samples were evaluated by CIBERSORT algorithm. Association between each immune cell subtype and survival was inferred by the fractions of 22 immune cell types. “CancerSubtypes” R-package was employed to identify the three types of molecular classification and analyze the functional enrichment in each subclass. Response to immunotherapy and anticancer drug targets was predicted via TIDE algorithm and GDSC dataset. Results: Substantial variation reflecting individual difference was identified between cancer and normal tissues in the immune infiltration profiles. T cells CD4 memory activated, macrophages M1 were associated with improved overall survival (OS) as evaluated by univariate Cox regression and multivariate Cox. Three subtypes were identified by ´CancerSubtypes’ R-package and every sub-cluster possessed specific immune cell characterization. Meanwhile, Cluster II exhibited poor prognosis and sensitive response to immunotherapy. Conclusions: The cellular component of immune infiltration shows remarkable variation in OvCa. Profiling of immune infiltration is useful in prediction of prognosis of OvCa. The results from profiling might be considered in therapeutic modulation.


2020 ◽  
Author(s):  
Chenyan Fang ◽  
Yingli Zhang ◽  
Lingqin Zhao ◽  
Xi Chen ◽  
Liang Xia ◽  
...  

Abstract Background Systematic retroperitoneal lymphadenectomy has been widely used in the surgical treatment of advanced ovarian cancer patients. Nevertheless, the corresponding therapeutic may not provide a survival benefit. The aim of this study was to assess the effect of systematic retroperitoneal lymphadenectomy in such patients. Methods Patients with advanced ovarian cancer (stage III-IV, according to the classification presented by the International Federation of Gynecology and Obstetrics) who were admitted and treated in Zhejiang Cancer Hospital from January 2004 to December 2013 were enrolled and reviewed retrospectively. All patients were optimally or suboptimally debulked (absent or residual tumor <1 cm) and divided into two groups. Group A (no-lymphadenectomy group, n =170): patients did not undergo lymph node resection; lymph nodes resection or biopsy were selective. Group B (n=240): patients underwent systematic retroperitoneal lymphadenectomy. Results A total of 410 eligible patients were enrolled in the study. The patients’ median age was 51 years old (range, 28–72 years old). The 5-year overall survival (OS) and 2-year progression-free survival (PFS) rates were 78% and 24% in the no-lymphadenectomy group and 76% and 26% in the lymphadenectomy group (P=0.385 and 0.214, respectively). Subsequently, there was no significant difference in 5-year OS and 2-year PFS between the two groups stratified to histological types (serous type or non-serous type), the clinical evaluation of negative lymph nodes or with macroscopic peritoneal metastasis beyond pelvic (IIIB-IV). Multivariate Cox regression analysis indicated that systematic retroperitoneal lymphadenectomy was not a significant factor influencing the patients’ survival. Patients in the lymphadenectomy group had a higher incidence of postoperative complications (incidence of infection treated with antibiotics was 21.7% vs. 12.9% [P=0.027]; incidence of lymph cysts was 20.8% vs. 2.4% [P < 0.001]). Conclusions Our study showed that systematic retroperitoneal lymphadenectomy did not significantly improve survival of advanced ovarian cancer patients with residual tumor<1 cm or absent after cytoreductive surgery, and were associated with a higher incidence of postoperative complications.


2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 179-182 ◽  
Author(s):  
M. Ueda ◽  
Y. Terai ◽  
K. Kanda ◽  
M. Kanemura ◽  
M. Takehara ◽  
...  

Single-nucleotide polymorphism at −670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P= 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas −670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08–6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05–2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter −670 may be associated with the risk of cervical cancer in a Japanese population.


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