Correlation between preoperative serum levels of five biomarkers and relationships between these biomarkers and cancer stage in epithelial overian cancer

황종윤,나성훈,이향아,이동연 대한부인종양학회 2009 Journal of Gynecologic Oncology Vol.20 No.3

Objective: To examine the correlation among the preoperative serum levels of five biomarkers presumed to be useful for early detection of epithelial ovarian cancer and evaluate the relationships between serum levels of these five biomarkers and epithelial ovarian cancer stage. Methods: We analyzed 56 newly diagnosed epithelial ovarian cancer patients. Preoperative serum levels of leptin, prolactin, osteopontin (OPN), insulin-like growth factor-II, and CA-125 were determined by ELISA. We also examined the correlation between the serum levels of the biomarkers and ovarian cancer stage. Significant differences in the mean serum levels of two proteins, leptin and CA-125, were observed between stage subsets. Results: There was a significant negative correlation between prolactin and leptin and a significant positive correlation between prolactin and OPN. Of the five biomarkers, only the mean serum CA-125 level showed a significant positive correlation with cancer stage (Spearman ρ=0.24, p<0.01). OPN showed a marginally significant positive correlation with stage (Spearman ρ=0.14, p=0.07). Conclusion: We demonstrated the relationship between five biomarkers in epithelial ovarian cancer. These tumor markers may be useful in screening for ovarian cancer, in characterizing disease states, and in developing therapeutic interventions targeting these marker proteins. Large-scale studies that include potential confounding factors and modifiers are necessary to more accurately define the value of these novel biomarkers in ovarian cancer. Objective: To examine the correlation among the preoperative serum levels of five biomarkers presumed to be useful for early detection of epithelial ovarian cancer and evaluate the relationships between serum levels of these five biomarkers and epithelial ovarian cancer stage. Methods: We analyzed 56 newly diagnosed epithelial ovarian cancer patients. Preoperative serum levels of leptin, prolactin, osteopontin (OPN), insulin-like growth factor-II, and CA-125 were determined by ELISA. We also examined the correlation between the serum levels of the biomarkers and ovarian cancer stage. Significant differences in the mean serum levels of two proteins, leptin and CA-125, were observed between stage subsets. Results: There was a significant negative correlation between prolactin and leptin and a significant positive correlation between prolactin and OPN. Of the five biomarkers, only the mean serum CA-125 level showed a significant positive correlation with cancer stage (Spearman ρ=0.24, p<0.01). OPN showed a marginally significant positive correlation with stage (Spearman ρ=0.14, p=0.07). Conclusion: We demonstrated the relationship between five biomarkers in epithelial ovarian cancer. These tumor markers may be useful in screening for ovarian cancer, in characterizing disease states, and in developing therapeutic interventions targeting these marker proteins. Large-scale studies that include potential confounding factors and modifiers are necessary to more accurately define the value of these novel biomarkers in ovarian cancer.

난소암 조직에서 Ureaplasma urealyticum의 분리 배양과 검출

여태홍(Tae Hong Yeo),석원일(Won Il Seok),김홍열(Heung Yeol Kim) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.5

N/A Background & Objectives : According to recent studies, Mycoplasma DNA was positive in 20% of uterine cervical cancer tissue and 48% of gastric cancer tissue. It also showed the correlation with human cancers and infection of Mycoplasma. Ureaplasma urealyticum(U. urealyticum) is a bacteria of high infection rate in women's urogenital system, but it is difficult to find a report about the relations to cancer. So, the objectives of this studies are to investigate the infection rate of the U. urealyticum from Korean women's ovarian cancer, borderline ovarian cancer and benign ovarian tumor, and to discover the relationship between these ovarian tumors with U. urealyticum's infection. Methods : In obstetrics and gynecology department of Kosin medical college, the PCR procedure and cultivation was performed on extracted cancer tissues of 22 ovarian cancer patients and 5 borderline ovarian cancer patients who had operation, and it was also performed on 30 benign ovarian tumor patients as an control group. Results : The detection freguency of U. urealyticum in ovarian cancer tissue was 31.8% (7/22) which was higher than 13.3% (4/30) of benign ovarian tumor but had no statistical relation (p=0.318). In borderline ovarian cancer, the detection frequency was 0.0% (0/5). The infection frequency of U. urealyticum was 22.7% (5/22) in ovarian cancer tissue and 0.0% (0/5) in borderline ovarian tumor and 3.3% (1/30) in benign ovarian tumor, so the infection frequency was higher in ovarian cancer tissue than benign ovarian tumor which was showing statistical relation (p=0.024). The detection frequency of U. urealyticum from benign ovarian tumor tissue was 23.0% (3/13) in mature teratoma and 16.7% (1/6) in epithelial ovarian tumor, which was showing higher frequency in mature teratoma but had no statistical relation(p=0.589). The infection frequency was showed only in epithelial ovarian tumor as 16.7% (1/6) but also had no statistical relation(p=0.388). The detection frequency of U. urealyticum followed by the FIGO stage of malignant ovarian cancer was 33% in stage I and 30.8% (4/13) in stage III, which was higher in stage I but had no statistical relation(p=0.662). The infection frequency was 11.1% (1/9) in stage I and 30.8% (4/13) in stage III, which was higher in stage III but had no statistical relation(p=0.360). Conclusion : With the above results, there was no significant relation between U. urealyticum infection and ovarian cancer. There is, however, few study and case on ovarian cancer internally and externally. It is considered that more studies on the subject with much cases should be made.

난소암의 조기진단

남주현,목정은 울산대학교 의과대학 1993 울산의대학술지 Vol.2 No.2

Ovarian cancer is the leading cause of death from gynecologic malignancies. In 1992, it has been reported that the incidence of ovarian cancer was 3% of all female malignancies in Korea. During the last decade, the incidence of cervical cancer which is the most common one of female malignancies was gradually declining, however that of ovarian cancer tended to be slightly increasing probably because of changes in socioeconomic status of this country. Despite of aggressive debulking operation and intensive platinum-based combination chemotherapy, the overall survival rate for ovarian cancer has not changed appreciably over the last twenty years. One of the reasons for poor prognosis of ovarian cancer is that greater than 70% of patients with ovarian cancer is unfortunately detected after the disease has already spreaded beyond the pelvis because of the lack of early symptoms. The cure rate for these patients with advanced ovarian cancer is only 15-20%, This low survival rate is in marked contrast to that of as high as 90% with stage I disease. Therefore, development of early detection method for ovarian cancer would be the best way to reduce the mortality rate of this disease. Ultrasonography and serum tumor marker, CA 125 have been extensively studied for early detection of ovarian cancer. Recently, combined use of transvaginal color Doppler technique is studied to increase the specificity of the screening test. However, the value of these methods as a screening test is still debating. So far, unfortunately there is no conclusive method which has cost-effectiveness and perfect sensitivity and specificity for ovarian cancer screening. Moreover, the optimal population and interval for ovarian cancer screening are not currently defined. In this review, recent data of studies using ultrasound and serum marker, CA 125 and debating issues for ovarian cancer screening are discussed.

A hospital-based case-control study of identifying ovarian cancer using symptom index

김미경,김기동,김선민,김재원,박노현,송용상,강순범 대한부인종양학회 2009 Journal of Gynecologic Oncology Vol.20 No.4

Objective: Recently, a symptom index for identification of ovarian cancer, based on specific symptoms along with their frequency and duration, was proposed. The current study aimed at validation of this index in Korean population. Methods: A case-control study of 116 women with epithelial ovarian cancer and 209 control women was conducted using questionnaires on eight symptoms. These included pelvic/abdominal pain, urinary urgency/frequency, increased abdominal size/bloating, difficulty eating/feeling full. The symptom index was considered positive if any of the 8 symptoms present for <1 year that occurred>12 times per month. The symptoms were compared between ovarian cancer group and control group using chi-square test. Logistic regression analysis was used to determine whether the index predicted cancer. Sensitivity and specificity of the symptom index were also determined. Results: The symptom index was positive in 65.5% of women with ovarian cancer, in 31.1% of women with benign cysts, and in 6.7% of women on routine screening (ps<0.001). Significantly higher proportion of ovarian cancer patients were positive for each symptom as compared with control group (ps<0.001). Results from the logistic regression indicated that the symptom index independently predicted cancer (p<0.001; OR, 10.51; 95% CI, 6.14 to 17.98). Overall, the sensitivity and specificity of the symptom index were 65.5% and 84.7%, respectively. Analyses of sensitivity by stage showed that the index was positive in 44.8% of patients with stage Ⅰ/Ⅱ disease and in 72.9% of patients with stage Ⅲ/Ⅳ disease. Conclusion: The current study supported previous studies suggesting that specific symptoms were useful in identifying women with ovarian cancer. Objective: Recently, a symptom index for identification of ovarian cancer, based on specific symptoms along with their frequency and duration, was proposed. The current study aimed at validation of this index in Korean population. Methods: A case-control study of 116 women with epithelial ovarian cancer and 209 control women was conducted using questionnaires on eight symptoms. These included pelvic/abdominal pain, urinary urgency/frequency, increased abdominal size/bloating, difficulty eating/feeling full. The symptom index was considered positive if any of the 8 symptoms present for <1 year that occurred>12 times per month. The symptoms were compared between ovarian cancer group and control group using chi-square test. Logistic regression analysis was used to determine whether the index predicted cancer. Sensitivity and specificity of the symptom index were also determined. Results: The symptom index was positive in 65.5% of women with ovarian cancer, in 31.1% of women with benign cysts, and in 6.7% of women on routine screening (ps<0.001). Significantly higher proportion of ovarian cancer patients were positive for each symptom as compared with control group (ps<0.001). Results from the logistic regression indicated that the symptom index independently predicted cancer (p<0.001; OR, 10.51; 95% CI, 6.14 to 17.98). Overall, the sensitivity and specificity of the symptom index were 65.5% and 84.7%, respectively. Analyses of sensitivity by stage showed that the index was positive in 44.8% of patients with stage Ⅰ/Ⅱ disease and in 72.9% of patients with stage Ⅲ/Ⅳ disease. Conclusion: The current study supported previous studies suggesting that specific symptoms were useful in identifying women with ovarian cancer.

Does Human Epididymis Protein 4 (HE4) Have a Role in Prediction of Recurrent Epithelial Ovarian Cancer

Innao, Pedrada,Pothisuwan, Methasinee,Pengsa, Prasit Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.9

Background: Despite the fact that ovarian cancer is the seventh most common cancer in women worldwide and the fifth leading cause of cancer death, It is the most common cause of death due to reproductive cancers in Thailand where epithelial ovarian cancer (EOC) is commonly found. According to a Thai statistical analysis in 2010 by the Department of Medical Services, epithelial ovarian cancer was the sixth most common cancer in Thailand from 2001to 2003.The incidence of 5.1 per 100,000 women per year. Human epididymis protein 4 (HE4) is a novo diagnostic tumor marker for EOC. The combination of HE4 and carcinoma antigen 125 (CA 125) is a tool for detecting epithelial ovarian cancer (EOC) better than using CA 125 alone. Therefore, the researcher is interested in HE4 does have a role to predict recurrent epithelial ovarian cancer. Materials and Methods: The patients who had complete response after diagnosed with epithelial ovarian cancer by pathology, FIGO stage 3 or more had been treated through surgery and chemotherapy at the Sunpasitthiprasong Hospital from June 2014 until March 2016. The patients were followed up every three months, using tumor marker (CA 125, HE4,Carcinoma antigen 19-9) together with other checkup methods, such as rectovaginal examination, CXR every year and other imaging as indication. Afterwards, the data was analyzed for the ability of HE4 to detect recurrence of epithelial ovarian cancer. Results: In 47 patients in this study follow-up for 22 months after complete response treatment from surgery and chemotherapy in epithelial ovarian cancer, 23 had recurrent disease and HE4 titer rising. The patients with recurrent epithelial ovarian cancer demonstrated high levels of both HE4 and CA125 with sensitivity of 91.3% and 52.7% respectively, specificity of 87.5% and 95.6% and positive predictive values of 87.5% and 85.7%. HE4 can predict recurrent epithelial ovarian cancer (p-value=0.02242). Comparing HE4 and CA125 in predicting recurrent epithelial ovarian cancer HE4 had more potential than CA125 (p-value =0.8314). Conclusions: The present study showed HE4 to have a role in predicting recurrent epithelial ovarian cancer and HE4 is potentially better than CA125 as a marker for this purpose.

High expression of maternal embryonic leucine-zipper kinase (MELK) impacts clinical outcomes in patients with ovarian cancer and its inhibition suppresses ovarian cancer cells growth ex vivo

Yuji Ikeda,Sho Sato,Akira Yabuno,Daisuke Shintani,Aiko Ogasawara,Maiko Miwa,Makda Zewde,Takashi Miyamoto,Keiichi Fujiwara,Yusuke Nakamura,Kosei Hasegawa 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.6

Objective: Maternal embryonic leucine zipper kinase (MELK) is receiving an attentionas a therapeutic target in various types of cancers. In this study, we aimed to evaluate theprognostic significance of MELK expression in ovarian cancer using clinical samples, andassessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derivedovarian cancer cells as well as cell lines. Methods: Expression levels of MELK in 11 ovarian cancer cell lines were confirmed bywestern blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay. MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients byquantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluatedusing freshly-isolated primary ovarian cancer cells including spheroid formation condition. Results: MELK mRNA expression was significantly higher in ovarian cancer than in normalovaries (p<0.001), and high MELK mRNA expression was observed in patients with advancedstage, positive ascites cytology and residual tumor size. Patients with high MELK mRNAexpression showed shorter progression-free survival (p=0.001). Expression of MELK wasalso confirmed in 10 of 11 ovarian cancer cell lines tested, and the half maximal inhibitoryconcentration of MELK inhibitor, OTS167, ranged from 9.3 to 60 nM. Additionally, OTS167showed significant growth inhibitory effect against patient-derived ovarian cancer cells,regardless of their tumor locations, histologic subtypes and stages. Conclusions: We demonstrated MELK as both a prognostic marker and a therapeutic targetfor ovarian cancer using clinical ovarian cancer samples. MELK inhibition by OTS167 may bean effective approach to treat ovarian cancer patients.

Survival outcome of women with synchronous cancers of endometrium and ovary: a 10 year retrospective cohort study

Yong Kuei Lim,Rama Padma,Lilian Foo,Yin Nin Chia,Philip Yam,John Chia,HS Khoo-Tan,Swee Peng Yap,Richard Yeo 대한부인종양학회 2011 Journal of Gynecologic Oncology Vol.22 No.4

Objective: Synchronous occurrence of endometrial and ovarian tumors is uncommon, and they affect less than 10% of women with endometrial or ovarian cancers. The aim of this study is to describe the epidemiological and clinical factors; and survival outcomes of women with these cancers. Methods: This is a retrospective cohort study in a large tertiary institution in Singapore. The sample consists of women with endometrial and epithelial ovarian cancers followed up over a period of 10 years from 2000 to 2009. The epidemiological and clinical factors include age at diagnosis, histology types, grade and stage of disease. Results: A total of 75 patients with synchronous ovarian and endometrial cancers were identified. However, only 46 patients met the inclusion criteria. The median follow-up was 74 months. The incidence rate for synchronous cancer is 8.7% of all epithelial ovarian cancers and 4.9% of all endometrial cancers diagnosed over this time frame. Mean age at diagnosis was 47.3 years old. The most common presenting symptom was abnormal uterine bleeding (36.9%) and 73.9% had endometrioid histology for both endometrial and ovarian cancers. The majority of the women (78%) presented were at early stages of 1 and 2. There were 6 (13.6%) cases of recurrence and the 5 year cumulative survival rate was at 84%. Conclusion: In our cohort, we found that majority of women afflicted with synchronous cancer of the endometrium and ovary were younger at age of diagnosis, had early stage of cancer and good survival. Objective: Synchronous occurrence of endometrial and ovarian tumors is uncommon, and they affect less than 10% of women with endometrial or ovarian cancers. The aim of this study is to describe the epidemiological and clinical factors; and survival outcomes of women with these cancers. Methods: This is a retrospective cohort study in a large tertiary institution in Singapore. The sample consists of women with endometrial and epithelial ovarian cancers followed up over a period of 10 years from 2000 to 2009. The epidemiological and clinical factors include age at diagnosis, histology types, grade and stage of disease. Results: A total of 75 patients with synchronous ovarian and endometrial cancers were identified. However, only 46 patients met the inclusion criteria. The median follow-up was 74 months. The incidence rate for synchronous cancer is 8.7% of all epithelial ovarian cancers and 4.9% of all endometrial cancers diagnosed over this time frame. Mean age at diagnosis was 47.3 years old. The most common presenting symptom was abnormal uterine bleeding (36.9%) and 73.9% had endometrioid histology for both endometrial and ovarian cancers. The majority of the women (78%) presented were at early stages of 1 and 2. There were 6 (13.6%) cases of recurrence and the 5 year cumulative survival rate was at 84%. Conclusion: In our cohort, we found that majority of women afflicted with synchronous cancer of the endometrium and ovary were younger at age of diagnosis, had early stage of cancer and good survival.

LncRNA SNHG20 promotes cell proliferation and invasion by suppressing miR-217 in ovarian cancer

Xing Xuefeng,An Ming,Chen Tonghua 한국유전학회 2021 Genes & Genomics Vol.43 No.9

Background Ovarian cancer is the most common female gynecological malignancy. SNHG20, as a long non-coding RNA, has been proven to be an important regulator in the occurrence and development of various tumors. However, the potential mechanism of SNHG20 in ovarian cancer is unclear. Objective The present study was aimed to investigate the functions and mechanisms of SNHG20 in ovarian cancer. Methods The expression of SNHG20 and miR-217 in ovarian cancer tissues and cell lines was detected by qRT-PCR. CCK-8 assay was used to measure cell proliferation in transfected cells. The transwell assay was used to detect the relative invasion rate of transfected cells. The putative binding sites between SNHG20 and miR-217 were predicted by software LncBase v.2, and the interaction between SNHG20 and miR-217 was confrmed by dual-luciferase reporter assays and RIP assay. The rescue experiments were used to illustrate potential mechanisms. Results SNHG20 was upregulated in ovarian cancer tissues and cell lines. Overexpression of SNHG20 promoted ovarian cancer cell proliferation and invasion. MiR-217 was downregulated in ovarian cancer tissues and cells, and was negatively regulated by SNHG20. Moreover, miR-217 overexpression inhibited ovarian cancer cell proliferation and invasion. Furthermore, miR-217 mimic reversed the inhibitory efect of SNHG20 overexpression on the biological behavior of ovarian cancer cells. Conclusions SNHG20 promoted cell proliferation and invasion by sponging miR-217 in ovarian cancer. These results suggested that SNHG20 and miR-217 might provide new targets for therapeutic application in ovarian cancer.

Carboplatin/Paclitaxel과 한방치료를 병행하며 부분 관해 된 폐전이 동반 말기 난소암 1례

고은비,오재성 대한한방부인과학회 2022 大韓韓方婦人科學會誌 Vol.35 No.1

Objectives: The purpose of this study is to report the effect of combination treatment of Traditional Korean medicine (TKM) and chemotherapy on a ovarian cancer with lung metastasis patient. Methods: One ovarian cancer with lung metastasis patient was treated by TKM in conjunction with Carboplatin/paclitaxel since Feb. 2020. Repeat cycle every 3 weeks for 6 times. The patient has been treated with TKM at the same time. To evaluate the patient, symptoms were measured by Numeric Rating Scale (NRS), Eastern Cooperative Oncology Group (ECOG) and tumor size was measured by scanning with Computed Tomography (CT). Blood tests including cancer biomarker were conducted during treatment. Adverse events were evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 5.0. Results: After treatment with Carboplatin/paclitaxel and TKM during 2 months, the size of the ovarian cancer was decreased(Partial Response, PR), size and malignant pleural effusion at right lung disappeared. And no evidence of newly developed metastatic lesions. After 2 months, the tumor response was stable disease while improving the performance and other symptoms. Conclusions: This case provides us conjunctive treatment with Conventional and Eastern medicine may have substantial benefit for patients with end-stage ovarian cancer. Objectives: The purpose of this study is to report the effect of combination treatment of Traditional Korean medicine (TKM) and chemotherapy on a ovarian cancer with lung metastasis patient. Methods: One ovarian cancer with lung metastasis patient was treated by TKM in conjunction with Carboplatin/paclitaxel since Feb. 2020. Repeat cycle every 3 weeks for 6 times. The patient has been treated with TKM at the same time. To evaluate the patient, symptoms were measured by Numeric Rating Scale (NRS), Eastern Cooperative Oncology Group (ECOG) and tumor size was measured by scanning with Computed Tomography (CT). Blood tests including cancer biomarker were conducted during treatment. Adverse events were evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 5.0. Results: After treatment with Carboplatin/paclitaxel and TKM during 2 months, the size of the ovarian cancer was decreased(Partial Response, PR), size and malignant pleural effusion at right lung disappeared. And no evidence of newly developed metastatic lesions. After 2 months, the tumor response was stable disease while improving the performance and other symptoms. Conclusions: This case provides us conjunctive treatment with Conventional and Eastern medicine may have substantial benefit for patients with end-stage ovarian cancer.

Prognostic value of programmed cell death ligand-1 expression in ovarian cancer: an updated meta-analysis

( Jinlan Piao ),( Hyun Ji Lim ),( Maria Lee ) 대한산부인과학회 2020 Obstetrics & Gynecology Science Vol.63 No.3

Objective To investigate the prognostic significance of programmed cell death ligand-1 (PD-L1) in ovarian cancer. Methods PubMed, Embase, and Cochrane Library databases were searched to identify studies that examined the prognostic significance of immunohistochemically assessed PD-L1 expression in histologically confirmed ovarian cancer. Eleven studies on PD-L1 expression involving 1,296 patients with ovarian cancer were included in this meta-analysis. Pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were analyzed. Relationship between PDL1 expression, and overall survival (OS) or progression-free survival (PFS) among patients with ovarian cancer was assessed. Subgroup analysis was performed based on the race, histologic type, and tumor International Federation of Gynecology and Obstetrics stage to evaluate the source of heterogeneity. Begg’s Funnel plot and Egger’s linear test were used to evaluate publication bias. Random-effects model was implemented when significant between-study heterogeneity (I2>50%) was observed. Results We found no correlation between PD-L1 expression, and OS (HR, 1.13; 95% CI, 0.95-1.36; I²=78%) or PFS (HR, 1.07; 95% CI, 0.88-1.30; I²=75%) in ovarian cancer. Subgroup analyses showed that higher PD-L1 expression was associated with poor OS in non-Asian patients with ovarian cancer (HR, 1.26; 95% CI, 1.07-1.481; I²=59%). We found that upregulated PD-L1 expression to be a positive predictor for OS in serous ovarian cancer (HR, 0.98; 95% CI, 0.76- 1.26; I²=74%) and a negative predictor for OS in non-serous ovarian cancer (HR, 1.29; 95% CI, 1.03-1.61; I²=64%) Furthermore, high PD-L1 expression was found to be a negative predictor for PFS of patients with non-serous ovarian cancer (HR, 1.12; 95% CI, 0.96-1.29; I²=37%). Conclusion Our meta-analysis suggests that PD-L1 expression is not associated with patient risk for ovarian cancer.