Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk – Combined Results from Two Screening Trials
Steven J. SkatesMark H. GreeneSaundra S. BuysL. PhuongPowel BrownMarion PiedmonteGustavo C. RodriguezJohn O. SchorgeMark E. ShermanMary B. DalyThomas F. RutherfordWendy R. BrewsterDavid M. O’MalleyEdward E. PartridgeJohn F. BoggessCharles W. DrescherClaudine IsaacsAndrew BerchuckSusan M. DomchekSusan A. DavidsonRobert P. EdwardsSteven A. ElgKatie WakeleyKelly‐Anne PhillipsDeborah K. ArmstrongIra HorowitzCarol J. FabianJoan L. WalkerPatrick M. SlussWilliam J. WelchLori M. MinasianNora HorickCarol H. KastenSusan NayfieldDavid S. AlbertsDianne M. FinkelsteinKaren H. Lu
118
Citation
47
Reference
10
Related Paper
Citation Trend
Abstract:
Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL.Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls.Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years).Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR.Ovarian cancer is the most lethal gynecologic malignancy. Recently, several molecularly targeted anticancer agents have been developed for ovarian cancer; however, its prognosis remains extremely poor. The development of molecularly targeted therapy, as well as companion diagnostics, is required to improve outcomes for patients with ovarian cancer. In this study, to identify micro RNA s (mi RNA s) involved in the progression of ovarian cancer we analyzed serum mi RNA s in patients with ovarian cancer using mi RNA array and quantitative RT ‐ PCR and examined the anticancer properties of mi RNA expression in ovarian cancer cells. In patients with ovarian cancer, high amount of miR‐135a‐3p in serum samples was significantly associated with favorable clinical prognosis. The amount of miR‐135a‐3p was significantly decreased in patients with ovarian cancer compared with patients with ovarian cysts or normal ovaries. In SKOV ‐3 and ES ‐2 human ovarian cancer cells, enhanced expression of miR‐135a‐3p induced drug sensitivity to cisplatin and paclitaxel and suppressed cell proliferation and xenograft tumor growth. These findings suggest that miR‐135a‐3p may be considered as a biomarker and a therapeutic agent in ovarian cancer.
Cite
Citations (38)
The serum levels of Trx1 in patients with ovarian cancer were significantly higher than those in normal persons and patients with non-cancer inflammatory diseases. The level of Trx1 increased with the Figo stage. Ovarian cancer patients who were determined to be negative for CA125, were observed to have serum Trx1 levels as high as those of CA125-positive patients. In addition, patients with non-cancer inflammatory diseases had lower plasma Trx1 1 levels than did controls, showing that Trx1 allows clear distinctions between ovarian cancer and these non-cancer diseases. Combinational analysis of CA125 with Trx1 for the detection of ovarian cancer suggests that the diagnostic capacity of CA125 alone for the early detection of ovarian cancer, especially regarding sensitivity, is significantly improved by its combination with Trx1. Taken together, we conclude that serum Trx1 is useful for the early diagnosis of ovarian cancer.
Cite
Citations (17)
Abstract Mice have been used in ovarian cancer research mainly as hosts for cell lines derived from human ovarian tumors and ascites. Such models provided valuable information into the nature of metastatic ovarian cancer and possible treatment strategies. However, the complexity of genetic aberrations in human ovarian cancer cell lines precluded understanding of the initiating events responsible for ovarian cancer induction. Since the majority of ovarian cancer patients present at an advanced stage of the disease, it has been difficult to identify the precursor lesions that could be used to study the early morphologic and genetic changes in ovarian cancer. It is thought that the development of animal models in which ovarian cancer can be induced and studied during its early stages will enable better understanding of early ovarian cancer lesions and elucidate molecular events that support ovarian cancer progression. The difficulties in generating such models include the lack of an adequate ovary‐specific promoter, the uncertainty about the tissue of origin for different histologic types of ovarian cancer, and the deficiency in understanding the genetic aberrations responsible for ovarian cancer induction. In spite of these difficulties, the first advances toward generating mouse models for ovarian cancer have been made.
Cite
Citations (2)
Gynecologic oncology
Cite
Citations (3)
Cite
Citations (4)
Abstract Background Ovarian cancer greatly threatens the general health of women worldwide. Implementation of predictive prognostic biomarkers aids in ovarian cancer management. Methods Using online databases, the general expression profile, target-disease associations, and interaction network of PAWR were explored. To identify the role of PAWR in ovarian cancer, gene correlation analysis, survival analysis, and combined analysis of drug responsiveness and PAWR expression were performed. The predictive prognostic value of PAWR was further validated in clinical samples. Results PAWR was widely expressed in normal and cancer tissues, with decreased expression in ovarian cancer tissues compared with normal tissues. PAWR was associated with various cancers including ovarian cancer. PAWR formed a regulatory network with a group of proteins and correlated with several genes, which were both implicated in ovarian cancer and drug responsiveness. High PAWR expression denoted better survival in ovarian cancer patients (OS: HR = 0.84, P = 0.0077; PFS, HR = 0.86, P = 0.049). Expression of PAWR could predict platinum responsiveness in ovarian cancer and there was a positive correlation between PAWR gene effect and paclitaxel sensitivity. In 12 paired clinical samples, the cancerous tissues exhibited significantly lower PAWR expression than matched normal fallopian tubes. The predictive prognostic value of PAWR was maintained in a cohort of 50 ovarian cancer patients. Conclusions High PAWR expression indicated better survival and higher drug responsiveness in ovarian cancer patients. PAWR could be exploited as a predictive prognostic biomarker in ovarian cancer.
Cite
Citations (9)
Reliable tools for investigating ovarian cancer initiation and progression are urgently needed. While the use of ovarian cancer cell lines remains a valuable tool for understanding ovarian cancer, their use has many limitations. These include the lack of heterogeneity and the plethora of genetic alterations associated with extended in vitro passaging. Here we describe a method that allows for rapid establishment of primary ovarian cancer cells form solid clinical specimens collected at the time of surgery. The method consists of subjecting clinical specimens to enzymatic digestion for 30 min. The isolated cell suspension is allowed to grow and can be used for downstream application including drug screening. The advantage of primary ovarian cancer cell lines over established ovarian cancer cell lines is that they are representative of the original specific clinical specimens they are derived from and can be derived from different sites whether primary or metastatic ovarian cancer.
Cite
Citations (12)
Ovarian cancer is a major gynecologic cancer and common cause of gynecologic cancer death worldwide. However, the molecular mechanisms of ovarian cancer progression are still unclear. circular RNAs (circRNAs) are recently reported to be involved in cancer progression regulation but the potential functions of circRNAs in ovarian cancer remains unknown. In this study, we explored the expression of circKIF4A in ovarian cancer tissues. Then, a series of experiments were conducted to investigate how circKIF4A functioned in ovarian cancer in vitro and in vivo. The results revealed that circKIF4A was highly expressed in ovarian cancer tissues. Knockdown of circKIF4A suppressed cell proliferation and migration in ovarian cancer. Subsequent mechanism study revealed that circKIF4A acted as a competitive endogenous RNA (ceRNA) to promoted ovarian cancer progression by sponging miR-127 and upregulated the expression of Junctional adhesion molecule 3 (JAM3). Therefore, circKIF4A could be a novel biomarker and therapeutic target for ovarian cancer.
Competing Endogenous RNA
Tumor progression
Cite
Citations (19)
Reliable tools for investigating ovarian cancer initiation and progression are urgently needed. While the use of ovarian cancer cell lines remains a valuable tool for understanding ovarian cancer, their use has many limitations. These include the lack of heterogeneity and the plethora of genetic alterations associated with extended in vitro passaging. Here we describe a method that allows for rapid establishment of primary ovarian cancer cells form solid clinical specimens collected at the time of surgery. The method consists of subjecting clinical specimens to enzymatic digestion for 30 min. The isolated cell suspension is allowed to grow and can be used for downstream application including drug screening. The advantage of primary ovarian cancer cell lines over established ovarian cancer cell lines is that they are representative of the original specific clinical specimens they are derived from and can be derived from different sites whether primary or metastatic ovarian cancer.
Cite
Citations (6)