|Year : 2014 | Volume
| Issue : 7 | Page : 72-76
Advances in tumor markers of ovarian cancer for early diagnosis
X Dong1, X Men2, W Zhang1, P Lei1
1 Department of Hematology-Oncology and Geriatrics, Tianjin Medical University General Hospital, Tianjin 300020, China
2 Department of Internal Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300020, China
|Date of Web Publication||27-Mar-2015|
Department of Hematology-Oncology and Geriatrics, Tianjin Medical University General Hospital, Tianjin 300020
Department of Hematology-Oncology and Geriatrics, Tianjin Medical University General Hospital, Tianjin 300020
Source of Support: None, Conflict of Interest: None
Ovarian cancer often occurs in perimenopausal women. The mortality of ovarian cancer is in the first place among gynecological cancers because of no obvious early symptoms and the lack of effective diagnostic approach. Gene chips, proteomics, immunohistochemistry and other methods have become hot topics for early diagnosis of ovarian cancer. However, due to the variety of pathology and not clear enough of mechanism and etiology, there is still no ideal tumor markers with both high specific and sensitivity, which can be applied into clinical early diagnosis for ovarian cancer. Therefore, a new systematic method with high sensitivity and specificity for early diagnosis of ovarian cancer and new tumor markers need to be identified. We should make an examination of ovarian cancer in the early period in the crowd for early diagnosis and early treatment to further improve life quality of patients. This paper reviewed the recent advancements of tumor markers for early diagnosis of ovarian cancer.
Keywords: Early diagnosis, ovarian tumor, tumor marker
|How to cite this article:|
Dong X, Men X, Zhang W, Lei P. Advances in tumor markers of ovarian cancer for early diagnosis. Indian J Cancer 2014;51, Suppl S3:72-6
FNx01Xifeng Dong and Xiaoyan Men contribute equally to this work
| » Introduction|| |
Ovarian cancer is the fifth most common tumor in females of the world.  China has gradually entered the aging society and ovarian cancer incidence increased year by year.  Its mortality rate ranked to first in gynecological tumors. The occurrence of ovarian cancer had a trend of younger in recent years. ,, Due to no obvious clinical symptoms in the early period, most ovarian cancer was found at later period. The main screening methods are transvaginal ultrasonography, serum CA-125 and so on.  Clinical practice revealed that these approaches had some limitations. Therefore, finding reliable tumor markers for early diagnosis of ovarian cancer is urgent. This paper reviewed the research progress of tumor markers for early diagnosis of ovarian cancer.
| » Status of Diagnosis and Treatment of Ovarian Cancer|| |
Ovarian cancer often occurs in perimenopausal women. The incidence of ovarian cancer ranked the third among female cancer, only after cervical cancer and endometrial cancer.  About 60-70% of ovarian cancer patients are already in phase III-IV or with abdominal metastasis when diagnosed. , Ovarian cancer is often asymptomatic in the early period and in the later period patient will have abdominal distension, abdominal mass, gastrointestinal symptoms and symptoms related to tumor infiltration or compression. Although the treatments like surgery, radiotherapy and chemotherapy are continuous improved, the 5-year survival rate is still around 30%, and the prognosis is poor.  According to statistics, the number of new ovarian cancer cases was estimated at 21,980, and the deaths were estimated as high as 14,270 in the US in 2014.  A 5-year survival rate of patients with stage I ovarian cancer can be as high as >90% and the majority of them can be cured by surgery.  And therefore early diagnosis of ovarian cancer is the key to improving the 5-year survival rate of patients. It is demonstrated that 77% of endometrial cancer, 55% of breast cancer and 83% of cervical cancer can be early diagnosed through related examinations; however, only 23% of ovarian cancer can be early diagnosed.  Therefore, the early diagnosis of ovarian cancer is still in the research, and there is no definite markers, which can be used in clinical. This showed that if ovarian cancer can be screened in healthy people for early diagnosis and early treatment, the life quality of patients with ovarian cancer can be improved, and survival can be prolonged.
Screening of tumor markers through gene chip technology
Gene chip technology has been widely used in many field, including tumor-related gene research, tumor gene expression profile analysis, tumor molecular classification and tumor gene mutations. It has a great advantage on the study of tumor biology. In recent years, this technology has also been used in ovarian cancer research.  The advantage of gene chip technology is that, it can analyze the expression of thousands of genes simultaneously. So we can detect differentially expressed genes by comparing the serum or tissue of patients with ovarian cancer, healthy people and patients with benign tumors. Studies found abnormal methylation of DNA were closely related with tumor development. , And different tumors had their specific patterns of abnormal methylation of DNA. So difference methylated hybridization based on chip technology will be the new direction of cancer research. The changes of cancer cells in 5-methylcytosine terminal are mainly hypomethylation of DNA and hypermethylation of CpG Islands.  Gene methylation is mainly caused by methylation of normal silencing repetitive sequence. Activation of oncogene transcripts, and activation of latent transposon or chromosomal instability lead to hypomethylation of gene. While the abnormal DNA of CpG island appears hypermethylation and histone modifications. These events result in the nonactivated state of transcription and gene silence. This change is likely to be an early event in tumorigenesis.  So based on this feature, methylated genes may be detected and verified to make sure if it can be applied in clinical. Some scholars use this method to detect tissues of ovarian cancer. ,, The abnormal methylations of SFN, TMS1, and WT1 occurs frequently in ovarian clear cell adenocarcinoma.  And the methylation is different between low-grade malignant and highly malignant ovarian cancer. Abnormal methylation of RASSF1A, APC, GSTP1 and MGMT are found in low malignant ovarian cancer.  Moreover, heterochromatin hypomethylation and remodeling are commonly occurred near the centromeres of the 1 st and the 16 th chromosome in ovarian cancer.  A recent research detected the abnormal DNA methylation sites in tumor tissues from patients with primary epithelial ovarian cancer or benign ovarian diseases. 182 hypermethylation sites and 64 hypomethylation sites have been screened, and cytosine-phosphate-guanosine islands of EGFLAM, LSM2 and CDKN2A promoters were found to be hypomethylation, which may be potential tumor markers ovarian cancer. 
Advantages of DNA methylation investigations are as follows: First, DNA has better chemical stability than RNA and protein. Even low concentrations of methylation can be amplified using polymerase chain reaction technology to verification.  In addition, the amplify is limited to a single region rather than screening the entire mutated gene, which not only saves supplies, but also has highly targeted. The most important point is the material in serum. Serum is easy to be obtained, and this test meets the condition of clinical screening. This is a new approach in the current applications to test the stability of screened abnormal methylated genes. In addition, although there are many studies on gene methylation of ovarian cancer, the results are not consistent. Considering the differences of prevalence populations, types of ovarian cancer, the differences of experimental platforms and designs, the methylated gene or silence gene of ovarian cancer is still not clear. Therefore, the sample size needs to be increased, and the standard of experimental platform need to be consistent in future experiments to clear differentially methylated gene.
BRCA1 and BRCA2 genes are high-risk genes of ovarian cancer. Jazaeri.  test patients with ovarian cancer through cDNA gene chip methods, including 18 cases carrying high-risk BRCA1 gene and 16 cases carrying BRCA2 gene. Totally, 110 differentially expressed genes were detected. Ovarian cancer carrying BRCA-1 gene is highly correlated with AKT1 and UBL1 while lowly correlated with PTEN. However, ovarian cancer carrying BRCA-2 gene is closely associated with WNT2, SFRP4 and lowly correlated with PTEN. Further studies indicated that there is a strong correlation between BRCA-1 gene silence and highly differentiated ovarian cancer. , So this method can screen healthy people that carry high-risk genes to reduce their risks of having ovarian cancer. Unfortunately, the application of this method has some limitations. Screening objects only include a population with high-risk factors, rather than the general population. So it is not the best screening approach.
Serum proteomics screening tumor markers
Serum proteomics is a study based on proteome. It studies expression profiles of all proteins in the body on a particular state through appropriate protein analysis technology. Serum proteomics is widely used in screening and identification of tumor markers. And it has showed significant theoretical value and broad clinical application. Petricoin et al.  got five differential genes through flight mass spectrometry (MS) in 2002. And they analyzed serum proteins of 50 patients with ovarian cancer and 66 healthy women by C16 hydrophobic protein chip. This proteomic pattern can be used to analysis and distinguish populations with benign ovarian tumors or with cancers and healthy people. The sensitivity is 100%, and the specificity is 95%. , Since then many scholars at home or abroad screened differential gene of ovarian cancer through different MS. Russian scholars established diagnosis model through Clinprotools system, and the diagnostic sensitivity could be achieved to 100%.  Another research compared serum protein profiles from 36 epithelial ovarian cancer cases with 30 healthy controls using surface-enhanced laser desorption/ionization time-of-flight (TOF)-MS, obtained 15 peaks up-regulated and 14 down-regulated with 100% sensitivity and 93.33% specificity, indicating that this approach is useful to diagnose ovarian cancer. 
Immunohistochemistry screening tumor markers
There are many types of ovarian cancer. Research found that different kinds of ovarian cancers have their unique tumor markers. For example, the expression level of follistatin was highest in mucinous ovarian cancer, followed by ovarian endometrioid adenocarcinoma, clear cell carcinoma, squamous cell carcinoma, serous carcinoma.  Therefore, ovarian cancer should be studied according to different types to determine the specific tumor markers of each kind of ovarian cancer. Mucinous ovarian cancer accounts for 12-15% of ovarian cancers, and compared with other types of epithelial ovarian cancer, mucinous ovarian cancer is a significant difference clinically and morphologically. Autoantibodies sequence can be used to clear biomarkers in the pathogenesis of ovarian cancer. , Increasing studies focused on this hot issue. It has been found that titers of 9 autoantibodies were significantly increased in the early period of mucinous ovarian cancer. And 8 autoantibodies among them were found overexpressed by immunohistochemical methods.  T cells and antibodies belonging to the immune system in cancer patients will response to tumor antigen. So the detection of autoantibodies has a certain role to the detection of biomarkers. And the detection can reveal that this special antigen plays an important role in the pathophysiology of cancer. So the detection of autoantibodies no doubt will become a new method to early diagnosing ovarian cancer. However, there are only a few researches on this field currently, and the researches are all targeted at mucinous ovarian cancer. Research of other types of ovarian cancer one this area has not been reported.
B7-H4 and lysophosphatidic acid
So far although there are many research methods, markers that can be used in clinical are still not established. B7-H4 and lysophosphatidic acid (LPA) are two markers that have gotten more attention recently. B7-H4 is a new member of T cell costimulatory molecule B7 family, which has been recently discovered. B7-H4 can reduce T cell immunity through inhibiting proliferation of T cells, synthesis of cytokines and cell cycle progression.  Many studies on the expression of B7-H4 in ovarian cancer suggested that the expression was significantly higher in ovarian cancer while in normal ovarian tissue B7-H4 was hardly expressed. ,,,, And therefore, it can be considered as an important marker for early-stage ovarian cancer diagnosis. Moore et al. detected serum proteins and found that human epididymis protein 4 (HE4) has the highest sensitivity in diagnosing phase I/II ovarian cancer. The sensitivity was up to 62.4-82.7% and the specificity was up to 96%. Therefore, some researchers believed that so far HE4 is a marker with high sensitivity for early diagnosis of ovarian cancer. 
lysophosphatidic acid in plasma is a recently discovered tumor marker. Its plasma concentration is significantly different between benign and malignant tumors. LPA has three subtypes: LPA1, LPA2, and LPA3. Wang et al., identified that LPA was highly expressed in ovarian cancer and LPA can stimulate growth and metastasis of ovarian cancer cells.  And it was confirmed that LPA could be a screening marker.  Others have found that the plasma level of LPA in patients with stage I ovarian cancer was nearly 3 times higher than that in patients with benign ovarian tumors and 7 times higher than that in healthy control group, which further confirmed the reliability of LPA as a tumor marker. , Despite these, the applications of these two tumor markers in clinical for early-stage ovarian cancer screening needs to be further confirmed.
| » Traditional Diagnostic Approaches for Ovarian Cancer|| |
Currently, traditional methods for screening or diagnosing ovarian cancer mainly include serum CA-125, color Doppler ultrasound, laparoscopy, cytologic examination and so on. ,, Due to the diagnosis rate for early-stage ovarian cancer through single method is not high, combinative application is often needed. , However, the economic burden on patients is increased.
Testing of serum CA-125
CA-125 is currently considered to be the best and the most widely used tumor marker for ovarian cancer.  About 80% of patients with advanced ovarian cancer have the elevation of CA-125. But only 50-60% of patients with early-stage ovarian cancer have the increased CA-125. In addition, single CA-125 detection may cause false positive, due to that increase of CA-125 have also been found in other cancers, such as pancreatic cancer, breast cancer, bladder cancer, liver cancer, lung cancer. ,,,, And diverticulitis, cirrhotic, endometriosis and other benign diseases may also produce a high level of CA-125. , In some physiological conditions, the level of CA-125 may be elevated such as in menstruation or pregnancy.  So only CA-125 can't be an early indicator for screening ovarian cancer.  And CA-125 is strongly associated with serous ovarian cancer while it is not significantly associated with other ovarian tumors, such as mucinous ovarian cancer.  So it has some limitations. New biological indicators for early warning or diagnosis of ovarian cancer are needed to be found further.
Transvaginal ultrasonography can observe morphology of ovarian more clearly. It can suggest the degree of malignancy of ovarian cancer to a certain extent. Many studies suggested transvaginal ultrasonography can be used as a method for screening early-stage ovarian cancer.  Currently, ovarian morphology scoring system is often applied to assess ovarian cancer. The results showed the sensitivity was up to 98.1%, and the specificity was up to 80.8%. The positive predictive value was 40.9%, and the negative predictive value was 99.1%. But this scoring system has no uniform standards. And there is no case-control study with a large sample to clear if there is statistically significant difference with other methods. There are a lot of neovascularization in cancer. So we can detect the pulsatility index and resistance index by Doppler. It can diagnose ovarian cancer >2 cm. For ovarian cancer <2 cm, the effect of screening is not clear. 
In addition, laparoscopy can be performed if ovarian tumor was found. This is an invasive examination and can't be a routine screening method. Currently, the most effective screening method is considered with a minimum positive predictive value and specificity, which are >90% and combined diagnosis is best.
| » Perspective|| |
Ovarian cancer is one of the three severe cancers in female reproductive system malignancy. Currently, surgical treatment, chemotherapy, radiotherapy, bio-targeted therapy and other technologies have improved. But the long-term survival rate is still low. Therefore, early diagnosis and treatment are very important. In recent years, many scholars at home and abroad explored the methods and indicators for early diagnosis of ovarian cancer through a variety of methods. Ideal tumor marker should reflect tumor growth and metastasis with a quantitative relationship. It should have high sensitivity and high specificity. It should be noninvasive, reproducible, inexpensive and easy to be accepted. Therefore, early diagnosis of ovarian cancer still needs further exploration. The further research can be proteomics and bioinformatics of serum and tissue samples using the currently advanced liquid chip-TOF MS technology for identification and extraction of new biomarkers spectrum. In addition, the immune system will change if the body has a tumor. So we can test the quantity and index of immune cell subsets in peripheral blood through flow cytometry and establish early warning indicators for immune status of ovarian cancer. And we can select clinical-sensitive imaging diagnostic methods, pathology, examination, and clinical data to establish an integrated, relatively specific indicator system for tumor early warning. And then we can improve the early warning and early diagnosis of ovarian cancer.
| » Acknowledgements|| |
This project is supported by Tianjin Health Bureu (No. 2011KZ116, no. 2010KZ106), Tianjin Natural Science Foundation (No.14JCYBJC27800, no. 10JCYBJC23700).
| » References|| |
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9 29.
Wang B, Liu SZ, Zheng RS, Zhang F, Chen WQ, Sun XB. Time trends of ovarian cancer incidence in China. Asian Pac J Cancer Prev 2014;15:191 3.
Lee JY, Kim EY, Jung KW, Shin A, Chan KK, Aoki D, et al. Trends in gynecologic cancer mortality in East Asian regions. J Gynecol Oncol 2014;25:174 82.
Wu QJ, Vogtmann E, Zhang W, Xie L, Yang WS, Tan YT, et al. Cancer incidence among adolescents and young adults in urban Shanghai, 1973 2005. PLoS One 2012;7:e42607.
Kim K, Zang R, Choi SC, Ryu SY, Kim JW. Current status of gynecological cancer in China. J Gynecol Oncol 2009;20:72 6.
Roupa Z, Faros E, Raftopoulos V, Tzavelas G, Kotrotsiou E, Sotiropoulou P, et al. Serum CA 125 combined with transvaginal ultrasonography for ovarian cancer screening. In Vivo 2004;18:831 6.
Dhillon PK, Yeole BB, Dikshit R, Kurkure AP, Bray F. Trends in breast, ovarian and cervical cancer incidence in Mumbai, India over a 30 year period, 1976 2005: An age period cohort analysis. Br J Cancer 2011;105:723 30.
Colombo N, Peiretti M, Garbi A, Carinelli S, Marini C, Sessa C; ESMO Guidelines Working Group. Non epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow up. Ann Oncol 2012;23 Suppl 7: vii20 6.
Argento M, Hoffman P, Gauchez AS. Ovarian cancer detection and treatment: Current situation and future prospects. Anticancer Res 2008;28:3135 8.
Ozols RF, Bookman MA, Connolly DC, Daly MB, Godwin AK, Schilder RJ, et al. Focus on epithelial ovarian cancer. Cancer Cell 2004;5:19 24.
Colombo N, Van Gorp T, Parma G, Amant F, Gatta G, Sessa C, et al. Ovarian cancer. Crit Rev Oncol Hematol 2006;60:159 79.
Taylor DD, Gercel Taylor C, Parker LP. Patient derived tumor reactive antibodies as diagnostic markers for ovarian cancer. Gynecol Oncol 2009;115:112 20.
Chon HS, Lancaster JM. Microarray based gene expression studies in ovarian cancer. Cancer Control 2011;18:8 15.
Peedicayil J. The role of DNA methylation in the pathogenesis and treatment of cancer. Curr Clin Pharmacol 2012;7:333 40.
Luczak MW, Jagodzinski PP. The role of DNA methylation in cancer development. Folia Histochem Cytobiol 2006;44:143 54.
Plitta B, Giel Pietraszuk M, Markiewicz WT, Barciszewski J. Cytosine methylation in DNA and its role in cancer therapy. Postepy Biochem 2011;57:24 32.
Kurkjian C, Kummar S, Murgo AJ. DNA methylation: Its role in cancer development and therapy. Curr Probl Cancer 2008;32:187 235.
Koukoura O, Spandidos DA, Daponte A, Sifakis S. DNA methylation profiles in ovarian cancer: Implication in diagnosis and therapy (Review). Mol Med Rep 2014;10:3 9.
Jones A, Teschendorff AE, Li Q, Hayward JD, Kannan A, Mould T, et al. Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development. PLoS Med 2013;10:e1001551.
Wang J, Yu L, Cai J, Jia J, Gao Y, Liang M, et al. The role of EZH2 and DNA methylation in hMLH1 silencing in epithelial ovarian cancer. Biochem Biophys Res Commun 2013;433:470 6.
Kaneuchi M, Sasaki M, Tanaka Y, Shiina H, Yamada H, Yamamoto R, et al. WT1 and WT1 AS genes are inactivated by promoter methylation in ovarian clear cell adenocarcinoma. Cancer 2005;104:1924 30.
Makarla PB, Saboorian MH, Ashfaq R, Toyooka KO, Toyooka S, Minna JD, et al. Promoter hypermethylation profile of ovarian epithelial neoplasms. Clin Cancer Res 2005;11:5365 9.
Barton CA, Hacker NF, Clark SJ, O′Brien PM. DNA methylation changes in ovarian cancer: Implications for early diagnosis, prognosis and treatment. Gynecol Oncol 2008;109:129 39.
Gu XH, Lu Y, Ma D, Liu XS, Guo SW. Model of aberrant DNA methylation patterns and its applications in epithelial ovarian cancer. Zhonghua Fu Chan Ke Za Zhi 2009;44:754 9.
Wittenberger T, Sleigh S, Reisel D, Zikan M, Wahl B, Alunni Fabbroni M, et al. DNA methylation markers for early detection of women′s cancer: Promise and challenges. Epigenomics 2014;6:311 27.
Jazaeri AA. Molecular profiles of hereditary epithelial ovarian cancers and their implications for the biology of this disease. Mol Oncol 2009;3:151 6.
Zikán M, Pohlreich P, Freitag P, Janousek M, Pavlista D, Fischerová D, et al. Inactivation of BRCA1, BRCA2 and p53 genes in sporadic ovarian cancer. Ceska Gynekol 2008;73:298 302.
Hilton JL, Geisler JP, Rathe JA, Hattermann Zogg MA, DeYoung B, Buller RE. Inactivation of BRCA1 and BRCA2 in ovarian cancer. J Natl Cancer Inst 2002;94:1396 406.
Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 2002;359:572 7.
Tessitore A, Gaggiano A, Cicciarelli G, Verzella D, Capece D, Fischietti M, et al. Serum biomarkers identification by mass spectrometry in high mortality tumors. Int J Proteomics 2013;2013:125858.
Ziganshin RKh, Alekseev DG, Arapidi GP, Ivanov VT, Moshkovskii SA, Govorun VM. Serum proteome profiling for ovarion cancer diagnosis using ClinProt magnetic bead technique and MALDI TOF mass spectrometry. Biomed Khim 2008;54:408 19.
Zhang WY, Zhu LR, Zheng YH, Zhou L, Zhang JZ, Wu JH, et al. Study for drug resistance of epithelial ovarian cancer by serum protein profiling. Zhonghua Yi Xue Za Zhi 2009;89:1326 9.
Ren P, Chen FF, Liu HY, Cui XL, Sun Y, Guan JL, et al. High serum levels of follistatin in patients with ovarian cancer. J Int Med Res 2012;40:877 86.
Kim JH, Herlyn D, Wong KK, Park DC, Schorge JO, Lu KH, et al. Identification of epithelial cell adhesion molecule autoantibody in patients with ovarian cancer. Clin Cancer Res 2003;9:4782 91.
Tang L, Yang J, Ng SK, Rodriguez N, Choi PW, Vitonis A, et al. Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer. Eur J Cancer 2010;46:170 9.
Smith JB, Stashwick C, Powell DJ Jr. B7 H4 as a potential target for immunotherapy for gynecologic cancers: A closer look. Gynecol Oncol 2014;134:181 9.
Salceda S, Tang T, Kmet M, Munteanu A, Ghosh M, Macina R, et al. The immunomodulatory protein B7 H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Exp Cell Res 2005;306:128 41.
Tringler B, Liu W, Corral L, Torkko KC, Enomoto T, Davidson S, et al. B7 H4 overexpression in ovarian tumors. Gynecol Oncol 2006;100:44 52.
Simon I, Katsaros D, Rigault de la Longrais I, Massobrio M, Scorilas A, Kim NW, et al. B7 H4 is over expressed in early stage ovarian cancer and is independent of CA125 expression. Gynecol Oncol 2007;106:334 41.
Simon I, Liu Y, Krall KL, Urban N, Wolfert RL, Kim NW, et al. Evaluation of the novel serum markers B7 H4, Spondin 2, and DcR3 for diagnosis and early detection of ovarian cancer. Gynecol Oncol 2007;106:112 8.
Cheng L, Jiang J, Gao R, Wei S, Nan F, Li S, et al. B7 H4 expression promotes tumorigenesis in ovarian cancer. Int J Gynecol Cancer 2009;19:1481 6.
Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol 2008;108:402 8.
Wang P, Wu X, Chen W, Liu J, Wang X. The lysophosphatidic acid (LPA) receptors their expression and significance in epithelial ovarian neoplasms. Gynecol Oncol 2007;104:714 20.
Sedláková I, Vávrová J, Tošner J, Hanousek L. Lysophosphatidic acid (LPA) - A perspective marker in ovarian cancer. Tumour Biol 2011;32:311 6.
Pua TL, Wang FQ, Fishman DA. Roles of LPA in ovarian cancer development and progression. Future Oncol 2009;5:1659 73.
Tanyi J, Rigó J Jr. Lysophosphatidic acid as a potential target for treatment and molecular diagnosis of epithelial ovarian cancers. Orv Hetil 2009;150:1109 18.
Lawrie TA, Medeiros LR, Rosa DD, da Rosa MI, Edelweiss MI, Stein AT, et al. Laparoscopy versus laparotomy for FIGO stage I ovarian cancer. Cochrane Database Syst Rev 2013;2:CD005344.
Fagotti A, Vizzielli G, Fanfani F, Costantini B, Ferrandina G, Gallotta V, et al. Introduction of staging laparoscopy in the management of advanced epithelial ovarian, tubal and peritoneal cancer: Impact on prognosis in a single institution experience. Gynecol Oncol 2013;131:341 6.
Testa A, Kaijser J, Wynants L, Fischerova D, Van Holsbeke C, Franchi D, et al. Strategies to diagnose ovarian cancer: New evidence from phase 3 of the multicentre international IOTA study. Br J Cancer 2014;111:680 8.
Zacharakis D, Thomakos N, Biliatis I, Rodolakis A, Simou M, Daskalakis G, et al. Ultrasonographic markers and preoperative CA 125 to distinguish between borderline ovarian tumors and stage I ovarian cancer. Acta Obstet Gynecol Scand 2013;92:285 92.
Arun Muthuvel V, Jaya V. Pre operative evaluation of ovarian tumors by risk of malignancy index, CA125 and ultrasound. Asian Pac J Cancer Prev 2014;15:2929 32.
Díaz Padilla I, Razak AR, Minig L, Bernardini MQ, María Del Campo J. Prognostic and predictive value of CA 125 in the primary treatment of epithelial ovarian cancer: Potentials and pitfalls. Clin Transl Oncol 2012;14:15 20.
Szwedziak K, Szymanski D, Strzelczyk J. CA 125 concentration in portal blood as a predictor of resectability in pancreatic tumor. Contemp Oncol (Pozn) 2013;17:394 9.
Lu YY, Wang HY, Hsia JY, Lin WY. FDG PET/CT for the preoperative nodal staging of non small cell lung cancer in a tuberculosis endemic country: Are maximum standardized uptake values useful? Thorac Cancer 2013;4:273 9.
Ahmadi H, Djaladat H, Cai J, Miranda G, Daneshmand S. Precystectomy serum levels of carbohydrate antigen 19 9, carbohydrate antigen 125, and carcinoembryonic antigen: Prognostic value in invasive urothelial carcinoma of the bladder. Urol Oncol 2014;32:648 56.
Partridge EE, Greenlee RT, Riley TL, Commins J, Ragard L, Xu JL, et al. Assessing the risk of ovarian malignancy in asymptomatic women with abnormal CA 125 and transvaginal ultrasound scans in the prostate, lung, colorectal, and ovarian screening trial. Obstet Gynecol 2013;121:25 31.
Moore LE, Pfeiffer RM, Zhang Z, Lu KH, Fung ET, Bast RC Jr. Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cancer 2012;118:91 100.
Qureshi MO, Dar FS, Khokhar N. Cancer Antigen 125 as a marker of ascites in patients with liver cirrhosis. J Coll Physicians Surg Pak 2014;24:232 5.
Chowdhury MA, Xiubin Z, Wei H, Chenghao G. Cancer antigen 125 and ICAM 1 are together responsible for ascites in liver cirrhosis. Clin Lab 2014;60:653 8.
Xie YJ, Chen M, Chen SJ. Prediction of pregnancy outcomes with combined ultrasound scanning of yolk sacs and serum CA125 determinations in early threatened abortion. Clin Exp Obstet Gynecol 2014;41:186 9.
Braga F, Ferraro S, Mozzi R, Panteghini M. The importance of individual biology in the clinical use of serum biomarkers for ovarian cancer. Clin Chem Lab Med 2014;52:1625 31.
van Altena AM, de Hullu JA, Massuger LF. Letter commenting on the article "CA 125 expression pattern, prognosis and correlation with serum CA 125 in ovarian tumor patients" (104:508 515) by Hogdall, et al. and on the Editorial "CA 125: Megadaltons of novel opportunities" (104:505 507). Gynecol Oncol 2007;107:355 6.
van Nagell JR Jr, Hoff JT. Transvaginal ultrasonography in ovarian cancer screening: Current perspectives. Int J Womens Health 2013;6:25 33.
Testa AC, Ajossa S, Ferrandina G, Fruscella E, Ludovisi M, Malaggese M, et al. Does quantitative analysis of three dimensional power Doppler angiography have a role in the diagnosis of malignant pelvic solid tumors? A preliminary study. Ultrasound Obstet Gynecol 2005;26:67 72.
|This article has been cited by|
||Mechanisms of Adiponectin Action in Fertility: An Overview from Gametogenesis to Gestation in Humans and Animal Models in Normal and Pathological Conditions
| ||Alix Barbe,Alice Bongrani,Namya Mellouk,Anthony Estienne,Patrycja Kurowska,Jérémy Grandhaye,Yaelle Elfassy,Rachel Levy,Agnieszka Rak,Pascal Froment,Joëlle Dupont |
| ||International Journal of Molecular Sciences. 2019; 20(7): 1526 |
|[Pubmed] | [DOI]|
||Presence and role of stem cells in ovarian cancer
| ||Natasa Kenda Suster,Irma Virant-Klun |
| ||World Journal of Stem Cells. 2019; 11(7): 383 |
|[Pubmed] | [DOI]|
||ADP-ribosylation factor-like 4C predicts worse prognosis in endometriosis-associated ovarian cancers
| ||Shiro Wakinoue,Tokuhiro Chano,Tsukuru Amano,Takahiro Isono,Fuminori Kimura,Ryoji Kushima,Takashi Murakami |
| ||Cancer Biomarkers. 2019; 24(2): 223 |
|[Pubmed] | [DOI]|
||Isolation of Circulating Tumor Cells of Ovarian Cancer by Transferrin Immunolipid Magnetic Spheres and Its Preliminary Clinical Application
| ||Li Zuo,Wei Niu,Anqi Li |
| ||Nano LIFE. 2019; 09(01n02): 1940001 |
|[Pubmed] | [DOI]|
||Aberrant Methylation Status of Tumour Suppressor Genes in Ovarian Cancer Tissue and Paired Plasma Samples
| ||Dana Dvorská,Dušan Braný,Bálint Nagy,Marián Grendár,Robert Poka,Beáta Soltész,Marianna Jagelková,Katarína Zelinová,Zora Lasabová,Pavol Zubor,Zuzana Danková |
| ||International Journal of Molecular Sciences. 2019; 20(17): 4119 |
|[Pubmed] | [DOI]|
||Clinical relationships between the rs2212020 and rs189897 polymorphisms of the ITGA9 gene and epithelial ovarian cancer
| ||Jinyang Liu,Ting Liu,Lin Liang,Junyu He,Manying Zhang,Yanshan Ge,Shan Liao,Yanhong Zhou,Keqiang Zhang |
| ||Journal of Genetics. 2019; 98(1) |
|[Pubmed] | [DOI]|
||Ovarian cancer stem cells and their role in drug resistance
| ||Zalitha Pieterse,Monica Angelica Amaya-Padilla,Terence Singomat,Mudra Binju,Bau Dilam Madjid,Yu Yu,Pritinder Kaur |
| ||The International Journal of Biochemistry & Cell Biology. 2019; 106: 117 |
|[Pubmed] | [DOI]|
||Knockdown of NRSF inhibits cell proliferation of ovarian cancer via activating Hippo pathway
| ||Pengfei Deng,Yan Zuo,Shuxian Feng,Zongtao Li,Wan Chen,Huawen Li,Xiaoyu Wang |
| ||Life Sciences. 2018; 215: 73 |
|[Pubmed] | [DOI]|
||pETM: a penalized Exponential Tilt Model for analysis of correlated high-dimensional DNA methylation data
| ||Hokeun Sun,Ya Wang,Yong Chen,Yun Li,Shuang Wang,John Hancock |
| ||Bioinformatics. 2017; 33(12): 1765 |
|[Pubmed] | [DOI]|
||The value of red cell distribution width in patients with ovarian cancer
| ||Yuanyuan Qin,Peng Wang,Zhibi Huang,Gaoming Huang,Jingguang Tang,Yi Guo,Ping Huang,Zhanfeng Lai,Faquan Lin |
| ||Medicine. 2017; 96(17): e6752 |
|[Pubmed] | [DOI]|
||The role of adiponectin in obesity-associated female-specific carcinogenesis
| ||Ganji Purnachandra Nagaraju,Balney Rajitha,Sheik Aliya,Rama P. Kotipatruni,Appiya Santharam Madanraj,Anthea Hammond,Dongkyoo Park,Srinivasulu Chigurupati,Afroz Alam,Subasini Pattnaik |
| ||Cytokine & Growth Factor Reviews. 2016; 31: 37 |
|[Pubmed] | [DOI]|