Generic placeholder image

Current Chemical Biology


ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Review Article

Ovarian Cancer Biomarkers: Headway Towards Early Diagnosis

Author(s): Zeba Mueed, Pankaj Kumar Rai, Seemab Siddique and Nitesh Kumar Poddar*

Volume 15, Issue 1, 2021

Published on: 21 January, 2021

Page: [109 - 125] Pages: 17

DOI: 10.2174/2212796815666210121095445

Price: $65


The advancements in cancer treatment have no significant effect on ovarian cancer [OC]. The lethality of the OC remains on the top list of gynecological cancers. The long term survival rate of the OC patients with the advanced stage is less than 30%. The only effective measure to increase the survivability of the patient is the detection of disease in stage I. The earlier the diagnosis, the more will be the chances of survival of the patient. But due to the absence of symptoms and effective diagnosis, only a few % of OC are detected in stage I. A valid, reliable having a high acceptance test is imperative to detect OC in its early stages. Currently, the most used approach for the detection of OC is the screening of CA-125 and transvaginal ultrasonography together. This approach has an efficacy of only 30-45%. A large number of biomarkers are also being explored for their potential use in the early screening of OC, but no success is seen so far. This review provides an overview of the biomarkers being explored for early-stage diagnosis of OC and increasing the current long-term survival rates of OC patients.

Keywords: Ovarian cancer, diagnosis, biomarkers, chemoresistance, human epididymis protein 4 [HE4], carbohydrate antigen 125, bikunin, osteopontin, kallikreins.

Graphical Abstract
Siegel RL, Miller KD, Jemal A . Cancer statistics CA Cancer J Clin 2019; 69(1): 7-34..
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[] [PMID: 30207593]
Prat J, D’Angelo E, Espinosa I. Ovarian carcinomas: at least five different diseases with distinct histological features and molecular genetics. Hum Pathol 2018; 80: 11-27.
[] [PMID: 29944973]
Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY. Ovarian cancer. Nat Rev Dis Primers 2016; 2: 16061.
[] [PMID: 27558151]
Schwarz RF, Ng CK, Cooke SL, et al. Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis. PLoS Med 2015; 12(2): e1001789.
[] [PMID: 25710373]
Bashashati A, Ha G, Tone A, et al. Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling. J Pathol 2013; 231(1): 21-34.
[] [PMID: 23780408]
Davidson B. Recently identified drug resistance biomarkers in ovarian cancer. Expert Rev Mol Diagn 2016; 16(5): 569-78.
[] [PMID: 26895188]
Dochez V, Caillon H, Vaucel E, Dimet J, Winer N, Ducarme G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res 2019; 12(1): 28.
[] [PMID: 30917847]
Kirchhoff C, Habben I, Ivell R, Krull N. A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod 1991; 45(2): 350-7.
[] [PMID: 1686187]
Drapkin R, von Horsten HH, Lin Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res 2005; 65(6): 2162-9.
[] [PMID: 15781627]
Dewan R, Dewan A, Jindal M, Bhardawaj M. Diagnostic performance of serum human epididymis protein 4 (HE4) for prediction of malignancy in ovarian masses. Asian Pacific journal of cancer prevention. Asian Pac J Cancer Prev 2019; 20(4): 1103-8.
[] [PMID: 31030480]
Hellström I, Raycraft J, Hayden-Ledbetter M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res 2003; 63(13): 3695-700.
[PMID: 12839961]
Moore RG, Brown AK, Miller MC, 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(2): 402-8.
[] [PMID: 18061248]
James NE, Cantillo E, Oliver MT, et al. HE4 suppresses the expression of osteopontin in mononuclear cells and compromises their cytotoxicity against ovarian cancer cells. Clin Exp Immunol 2018; 193(3): 327-40.
[] [PMID: 29745428]
Wang H, Zhu L, Gao J, Hu Z, Lin B. Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells. Oncol Rep 2015; 33(1): 403-12.
[] [PMID: 25354091]
Zhu Y-F, Gao G-L, Tang S-B, Zhang Z-D, Huang Q-S. Effect of WFDC 2 silencing on the proliferation, motility and invasion of human serous ovarian cancer cells in vitro. Asian Pac J Trop Med 2013; 6(4): 265-72.
[] [PMID: 23608327]
Lee S, Choi S, Lee Y, Chung D, Hong S, Park N. Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer. J Obstet Gynaecol Res 2017; 43(1): 220-7.
[] [PMID: 27862665]
Kong X, Chang X, Cheng H, Ma R, Ye X, Cui H. Human epididymis protein 4 inhibits proliferation of human ovarian cancer cells via the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT pathways. Int J Gynecol Cancer 2014; 24(3): 427-36.
[] [PMID: 24557433]
Lu R, Sun X, Xiao R, Zhou L, Gao X, Guo L. Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. Biochem Biophys Res Commun 2012; 419(2): 274-80.
[] [PMID: 22342977]
Moore RG, Hill EK, Horan T, et al. HE4 (WFDC2) gene overexpression promotes ovarian tumor growth. Sci Rep 2014; 4: 3574.
[] [PMID: 24389815]
Zhu L, Zhuang H, Wang H, et al. Overexpression of HE4 (human epididymis protein 4) enhances proliferation, invasion and metastasis of ovarian cancer. Oncotarget 2016; 7(1): 729-44.
[] [PMID: 26575020]
Huang T, Jiang S-W, Qin L, et al. Expression and diagnostic value of HE4 in pancreatic adenocarcinoma. Int J Mol Sci 2015; 16(2): 2956-70.
[] [PMID: 25642754]
Bian J, Sun X, Li B, Ming L. Clinical significance of serum HE4, CA125, CA724, and CA19-9 in patients with endometrial cancer. Technol Cancer Res Treat 2017; 16(4): 435-9.
[] [PMID: 27562869]
Gąsiorowska E, Magnowska M, Iżycka N, Warchoł W, Nowak- Markwitz E. The role of HE4 in differentiating benign and malignant endometrial pathology. Ginekol Pol 2016; 87(4): 260-4.
[] [PMID: 27321096]
Yoon HI, Kwon O-R, Kang KN, et al. Diagnostic value of combining tumor and inflammatory markers in lung cancer. J Cancer Prev 2016; 21(3): 187-93.
[] [PMID: 27722145]
Zeng Q, Liu M, Zhou N, Liu L, Song X. Serum human epididymis protein 4 (HE4) may be a better tumor marker in early lung cancer. Clin Chim Acta 2016; 455: 102-6.
[] [PMID: 26851650]
Ribeiro JR, Gaudet HM, Khan M, et al. Human epididymis protein 4 promotes events associated with metastatic ovarian cancer via regulation of the extracelluar matrix. Front Oncol 2018; 7: 332.
[] [PMID: 29404274]
Zhuang H, Tan M, Liu J, et al. Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells. Mol Cancer 2014; 13(1): 243.
[] [PMID: 25362534]
Maxwell PH, Wiesener MS, Chang G-W, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999; 399(6733): 271-5.
[] [PMID: 10353251]
Dang CV, Semenza GL. Oncogenic alterations of metabolism. Trends Biochem Sci 1999; 24(2): 68-72.
[] [PMID: 10098401]
Zhong H, De Marzo AM, Laughner E, et al. Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Res 1999; 59(22): 5830-5.
[PMID: 10582706]
Diaz-Gonzalez JA, Russell J, Rouzaut A, Gil-Bazo I, Montuenga L. Targeting hypoxia and angiogenesis through HIF-1alpha inhibition. Cancer Biol Ther 2005; 4(10): 1055-62.
[] [PMID: 16294030]
Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene 2007; 26(22): 3279-90.
[] [PMID: 17496922]
Schulze WX, Deng L, Mann M. Phosphotyrosine interactome of the ErbB‐receptor kinase family. Molecular systems biology 2005; 1(1): 2005-2008..
Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature 2004; 432(7015): 332-7.
[] [PMID: 15549095]
Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer 2006; 6(5): 392-401.
[] [PMID: 16572188]
Cathcart J, Pulkoski-Gross A, Cao J. Targeting matrix metalloproteinases in cancer: bringing new life to old ideas. Genes Dis 2015; 2(`1): 26-34.
[] [PMID: 26097889]
Löffek S, Zigrino P, Angel P, Anwald B, Krieg T, Mauch C. High invasive melanoma cells induce matrix metalloproteinase-1 synthesis in fibroblasts by interleukin-1α and basic fibroblast growth factor-mediated mechanisms. J Invest Dermatol 2005; 124(3): 638-43.
[] [PMID: 15737206]
Ma J, Sawai H, Matsuo Y, et al. Interleukin-1α enhances angiogenesis and is associated with liver metastatic potential in human gastric cancer cell lines. J Surg Res 2008; 148(2): 197-204.
[] [PMID: 18395750]
Dabkeviciene D, Sasnauskiene A, Leman E, et al. mTHPC-mediated photodynamic treatment up-regulates the cytokines VEGF and IL-1alpha. Photochem Photobiol 2012; 88(2): 432-9.
[] [PMID: 22171990]
Gelfo V, Rodia MT, Pucci M, et al. A module of inflammatory cytokines defines resistance of colorectal cancer to EGFR inhibitors. Oncotarget 2016; 7(44): 72167-83.
[] [PMID: 27708224]
Stanam A, Gibson-Corley KN, Love-Homan L, Ihejirika N, Simons AL. Interleukin-1 blockade overcomes erlotinib resistance in head and neck squamous cell carcinoma. Oncotarget 2016; 7(46): 76087-100.
[] [PMID: 27738319]
Giancotti FG, Ruoslahti E. Integrin signaling. science 1999; 285(5430): 1028-1033..
Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 2010; 10(1): 9-22.
[] [PMID: 20029421]
Duperret EK, Dahal A, Ridky TW. Focal-adhesion-independent integrin-αv regulation of FAK and c-Myc is necessary for 3D skin formation and tumor invasion. J Cell Sci 2015; 128(21): 3997-4013.
[] [PMID: 26359297]
Karsenty G, Park R-W. Regulation of type I collagen genes expression. Int Rev Immunol 1995; 12(2-4): 177-85.
[] [PMID: 7650420]
Durbeej M, Larsson E, Ibraghimov-Beskrovnaya O, Roberds SL, Campbell KP, Ekblom P. Non-muscle alpha-dystroglycan is involved in epithelial development. J Cell Biol 1995; 130(1): 79-91.
[] [PMID: 7790379]
Akl MR, Nagpal P, Ayoub NM, et al. Molecular and clinical profiles of syndecan-1 in solid and hematological cancer for prognosis and precision medicine. Oncotarget 2015; 6(30): 28693-715.
[] [PMID: 26293675]
Tsuruta D, Kobayashi H, Imanishi H, Sugawara K, Ishii M, Jones JC. Laminin-332-integrin interaction: a target for cancer therapy? Curr Med Chem 2008; 15(20): 1968-75.
[] [PMID: 18691052]
Zhang Y, Zhou Z-H, Bugge TH, Wahl LM. Urokinase-type plasminogen activator stimulation of monocyte matrix metalloproteinase-1 production is mediated by plasmin-dependent signaling through annexin A2 and inhibited by inactive plasmin. J Immunol 2007; 179(5): 3297-304.
[] [PMID: 17709546]
Gao J, Hu Z, Liu D, et al. Expression of Lewis y antigen and integrin αv, β3 in ovarian cancer and their relationship with chemotherapeutic drug resistance. J Exp Clin Cancer Res 2013; 32(1): 36.
[] [PMID: 23725446]
Gao J, Hu Z, Liu J, et al. Expression of CD147 and Lewis y antigen in ovarian cancer and their relationship to drug resistance. Med Oncol 2014; 31(5): 920.
[] [PMID: 24692145]
Zhuang H, Gao J, Hu Z, Liu J, Liu D, Lin B. Co-expression of Lewis y antigen with human epididymis protein 4 in ovarian epithelial carcinoma. PLoS One 2013; 8(7): e68994.
[] [PMID: 23894390]
Liu J-J, Lin B, Hao Y-Y, et al. Lewis(y) antigen stimulates the growth of ovarian cancer cells via regulation of the epidermal growth factor receptor pathway. Oncol Rep 2010; 23(3): 833-41.
[PMID: 20127027]
Tollefsen DM. Heparin cofactor II modulates the response to vascular injury. Arterioscler Thromb Vasc Biol 2007; 27(3): 454-60.
[] [PMID: 17194895]
Liao WY, Ho CC, Hou HH, et al. Heparin co-factor II enhances cell motility and promotes metastasis in non-small cell lung cancer. J Pathol 2015; 235(1): 50-64.
[] [PMID: 25130770]
Valiente M, Obenauf AC, Jin X, et al. Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell 2014; 156(5): 1002-16.
[] [PMID: 24581498]
Lokman NA, Ween MP, Oehler MK, Ricciardelli C. The role of annexin A2 in tumorigenesis and cancer progression. Cancer Microenviron 2011; 4(2): 199-208.
[] [PMID: 21909879]
Ortiz-Zapater E, Peiró S, Roda O, et al. Tissue plasminogen activator induces pancreatic cancer cell proliferation by a non-catalytic mechanism that requires extracellular signal-regulated kinase 1/2 activation through epidermal growth factor receptor and annexin A2. Am J Pathol 2007; 170(5): 1573-84.
[] [PMID: 17456763]
Delys L, Detours V, Franc B, et al. Gene expression and the biological phenotype of papillary thyroid carcinomas. Oncogene 2007; 26(57): 7894-903.
[] [PMID: 17621275]
Angioli R, Capriglione S, Aloisi A, et al. Can HE4 predict platinum response during first-line chemotherapy in ovarian cancer? Tumour Biol 2014; 35(7): 7009-15.
[] [PMID: 24748235]
Chudecka-Głaz AM, Cymbaluk-Płoska AA, Menkiszak JL, Sompolska-Rzechuła AM, Tołoczko-Grabarek AI, Rzepka-Górska IA. Serum HE4, CA125, YKL-40, bcl-2, cathepsin-L and prediction optimal debulking surgery, response to chemotherapy in ovarian cancer. J Ovarian Res 2014; 7(1): 62.
[] [PMID: 25018782]
Gonzalez VD, Samusik N, Chen TJ, et al. Commonly occurring cell subsets in high-grade serous ovarian tumors identified by single-cell mass cytometry. Cell Rep 2018; 22(7): 1875-88.
[] [PMID: 29444438]
Yuan C, Li R, Yan S, Kong B. Prognostic value of HE4 in patients with ovarian cancer. Clin Chem Lab Med 2018; 56(7): 1026-34.
[] [PMID: 29420303]
Manente AG, Pinton G, Tavian D, Lopez-Rodas G, Brunelli E, Moro L. Coordinated sumoylation and ubiquitination modulate EGF induced EGR1 expression and stability. PLoS One 2011; 6(10): e25676.
[] [PMID: 21998680]
Zhao DY, Jacobs KM, Hallahan DE, Thotala D. Silencing Egr1 attenuates radiation-induced apoptosis in normal tissues while killing cancer cells and delaying tumor growth. Mol Cancer Ther 2015; 14(10): 2343-52.
[] [PMID: 26206332]
Wang K, Deng Q-T, Liao N, et al. Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy. Tumour Biol 2013; 34(1): 33-8.
[] [PMID: 22976542]
Gurler H, Yu Y, Choi J, Kajdacsy-Balla AA, Barbolina MV. Three-dimensional collagen type I matrix up-regulates nuclear isoforms of the microtubule associated protein tau implicated in resistance to paclitaxel therapy in ovarian carcinoma. Int J Mol Sci 2015; 16(2): 3419-33.
[] [PMID: 25658796]
Wu H, Huang M, Lu M, et al. Regulation of microtubule-associated protein tau (MAPT) by miR-34c-5p determines the chemosensitivity of gastric cancer to paclitaxel. Cancer Chemother Pharmacol 2013; 71(5): 1159-71.
[] [PMID: 23423488]
Russell SE, Hall PA. Do septins have a role in cancer? Br J Cancer 2005; 93(5): 499-503.
[] [PMID: 16136025]
Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002; 296(5573): 1655-7.
[] [PMID: 12040186]
Senapati S, Das S, Batra SK. Mucin-interacting proteins: from function to therapeutics. Trends Biochem Sci 2010; 35(4): 236-45.
[] [PMID: 19913432]
Argüeso P, Guzman-Aranguez A, Mantelli F, Cao Z, Ricciuto J, Panjwani N. Association of cell surface mucins with galectin-3 contributes to the ocular surface epithelial barrier. J Biol Chem 2009; 284(34): 23037-45.
[] [PMID: 19556244]
Timpte CS, Eckhardt AE, Abernethy JL, Hill RL. Porcine submaxillary gland apomucin contains tandemly repeated, identical sequences of 81 residues. J Biol Chem 1988; 263(2): 1081-8.
[PMID: 2826455]
Su Z, Graybill WS, Zhu Y. Detection and monitoring of ovarian cancer. Clin Chim Acta 2013; 415: 341-5.
[] [PMID: 23165217]
Gadducci A, Fuso L, Cosio S, et al. Are surveillance procedures of clinical benefit for patients treated for ovarian cancer?: A retrospective Italian multicentric study. Int J Gynecol Cancer 2009; 19(3): 367-74.
[] [PMID: 19407561]
Felder M, Kapur A, Gonzalez-Bosquet J, et al. MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress. Mol Cancer 2014; 13: 129.
[] [PMID: 24886523]
Kobayashi H, Yamada Y, Sado T, et al. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer 2008; 18(3): 414-20.
[] [PMID: 17645503]
Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol . 2009; 10: 327-40..
O’Brien TJ, Tanimoto H, Konishi I, Gee M. More than 15 years of CA 125: what is known about the antigen, its structure and its function. Int J Biol Markers 1998; 13(4): 188-95.
[] [PMID: 10228899]
O’Brien TJ, Beard JB, Underwood LJ, Dennis RA, Santin AD, York L. The CA 125 gene: an extracellular superstructure dominated by repeat sequences. Tumour Biol 2001; 22(6): 348-66.
[] [PMID: 11786729]
O’Brien TJ, Beard JB, Underwood LJ, Shigemasa K. The CA 125 gene: a newly discovered extension of the glycosylated N-terminal domain doubles the size of this extracellular superstructure. Tumour Biol 2002; 23(3): 154-69.
[] [PMID: 12218296]
Yin BW, Dnistrian A, Lloyd KO. Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene. Int J Cancer 2002; 98(5): 737-40.
[] [PMID: 11920644]
Maeda T, Inoue M, Koshiba S, et al. Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16). J Biol Chem 2004; 279(13): 13174-82.
[] [PMID: 14764598]
Bressan A, Bozzo F, Maggi CA, Binaschi M. OC125, M11 and OV197 epitopes are not uniformly distributed in the tandem-repeat region of CA125 and require the entire SEA domain. Dis Markers 2013; 34(4): 257-67.
[] [PMID: 23396293]
Bottoni P, Scatena R. The role of CA 125 as tumor marker: biochemical and clinical aspects. In: Scatena R, Ed. Advances in Cancer Biomarkers Advances in Experimental Medicine and Biology, vol 867 Dordrecht: Springer..
Gendler SJ, Spicer AP. Epithelial mucin genes. Annu Rev Physiol 1995; 57(1): 607-34.
[] [PMID: 7778880]
Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer 2009; 9(12): 874-85.
[] [PMID: 19935676]
Corfield AP. Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim Biophys Acta 2015; 1850(1): 236-52.
[] [PMID: 24821013]
Lakshmanan I, Ponnusamy MP, Das S, et al. MUC16 induced rapid G2/M transition via interactions with JAK2 for increased proliferation and anti-apoptosis in breast cancer cells. Oncogene 2012; 31(7): 805-17.
[] [PMID: 21785467]
Macauley MS, Crocker PR, Paulson JC. Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol 2014; 14(10): 653-66.
[] [PMID: 25234143]
Scholler N, Urban N. CA125 in ovarian cancer. Biomarkers Med 2007; 1(4): 513-23.
[] [PMID: 20477371]
Coticchia CM, Yang J, Moses MA. Ovarian cancer biomarkers: current options and future promise. J Natl Compr Canc Netw 2008; 6(8): 795-802.
[] [PMID: 18926090]
Gupta D, Lis CG. Role of CA125 in predicting ovarian cancer survival - a review of the epidemiological literature. J Ovarian Res 2009; 2: 13.
[] [PMID: 19818123]
Liu W, Wang Z, Ma J, et al. Elevated Serum Level of CA125 Is a Biomarker That Can Be Used to Alter Prognosis Determined by BRCA Mutation and Family History in Ovarian Cancer. Genet Test Mol Biomarkers 2017; 21(9): 547-54.
[] [PMID: 28799806]
Nadal R, Ojeda B, Artigas V, Bogunà I, Gich I, Ribé A. A Stratification of the normal range of CA125 after chemotherapy as a predictive factor in carcinoma of the ovary. J Clin Oncol 2006; 24(18_suppl): 5059-9.
Menon U, Griffin M, Gentry-Maharaj A. Ovarian cancer screening- current status, future directions. Gynecol Oncol 2014; 132(2): 490-5.
[] [PMID: 24316306]
Reinartz S, Failer S, Schuell T, Wagner U. CA125 (MUC16) gene silencing suppresses growth properties of ovarian and breast cancer cells. Eur J Cancer 2012; 48(10): 1558-69.
[] [PMID: 21852110]
Baum R, Hertel A, Baew-Christow T, Noujaim A, Hor G, Schmidt H. A novel Tc-99m labeled monoclonal antibody against CA125 (B43. 13) for radioimmunodetection of ovarian cancer-initial results. Nucl Med (Stuttg) 1992; 670: 672.
Reinartz S, Wagner U, Giffels P, Gruenn U, Schlebusch H, Wallwiener D. Immunological properties of a single-chain fragment of the anti-idiotypic antibody ACA125. Cancer Immunol Immunother 2000; 49(4-5): 186-92.
[] [PMID: 10941901]
Berek JS. Immunotherapy of ovarian cancer with antibodies: a focus on oregovomab. Expert Opin Biol Ther 2004; 4(7): 1159-65.
[] [PMID: 15268682]
Sabbatini P, Harter P, Scambia G, et al. Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO- the MIMOSA study. J Clin Oncol 2013; 31(12): 1554-61.
[] [PMID: 23478059]
Belisle JA, Gubbels JA, Raphael CA, et al. Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125). Immunology 2007; 122(3): 418-29.
[] [PMID: 17617155]
Weber GF. The metastasis gene osteopontin: a candidate target for cancer therapy. Biochim Biophys Acta 2001; 1552(2): 61-85.
[PMID: 11825687]
Rittling SR, Chambers AF. Role of osteopontin in tumour progression. Br J Cancer 2004; 90(10): 1877-81.
[] [PMID: 15138464]
Rakoff-Nahoum S, Medzhitov R. Toll-like receptors and cancer. Nat Rev Cancer 2009; 9(1): 57-63.
[] [PMID: 19052556]
Hsu H-P, Shan Y-S, Lai M-D, Lin P-W. Osteopontin-positive infiltrating tumor-associated macrophages in bulky ampullary cancer predict survival. Cancer Biol Ther 2010; 10(2): 144-54.
[] [PMID: 20495367]
Blasberg JD, Goparaju CM, Pass HI, Donington JS. Lung cancer osteopontin isoforms exhibit angiogenic functional heterogeneity. J Thorac Cardiovasc Surg 2010; 139(6): 1587-93.
[] [PMID: 19818970]
Jain S, Chakraborty G, Bulbule A, Kaur R, Kundu GC. Osteopontin: an emerging therapeutic target for anticancer therapy. Expert Opin Ther Targets 2007; 11(1): 81-90.
[] [PMID: 17150036]
Xu C, Li H, Yin M, Yang T, An L, Yang G. Osteopontin is involved in TLR4 pathway contributing to ovarian cancer cell proliferation and metastasis. Oncotarget 2017; 8(58): 98394-404.
[] [PMID: 29228698]
Cerne K, Hadzialjevic B, Skof E, Verdenik I, Kobal B. Potential of osteopontin in the management of epithelial ovarian cancer. Radiol Oncol 2019; 53(1): 105-15.
[] [PMID: 30712025]
Zhang J, Yamada O, Kida S, et al. Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells. Oncol Rep 2016; 36(4): 2357-64.
[] [PMID: 27498705]
Rangaswami H, Bulbule A, Kundu GC. Osteopontin: role in cell signaling and cancer progression. Trends Cell Biol 2006; 16(2): 79-87.
[] [PMID: 16406521]
Sodek J, Ganss B, McKee MD. Osteopontin. Crit Rev Oral Biol Med 2000; 11(3): 279-303.
[] [PMID: 11021631]
Kazanecki CC, Uzwiak DJ, Denhardt DT. Control of osteopontin signaling and function by post-translational phosphorylation and protein folding. J Cell Biochem 2007; 102(4): 912-24.
[] [PMID: 17910028]
Schorge JO, Drake RD, Lee H, et al. Osteopontin as an adjunct to CA125 in detecting recurrent ovarian cancer. Clin Cancer Res 2004; 10(10): 3474-8.
[] [PMID: 15161704]
Chesnais M, Lecuru F, Mimouni M, Ngo C, Fauconnier A, Huchon C. A pre-operative predictive score to evaluate the feasibility of complete cytoreductive surgery in patients with epithelial ovarian cancer. PLoS One 2017; 12(11): e0187245.
[] [PMID: 29117194]
Markman M, Bookman MA. Second-line treatment of ovarian cancer. Oncologist 2000; 5(1): 26-35.
[] [PMID: 10706647]
Mor G, Visintin I, Lai Y, et al. Serum protein markers for early detection of ovarian cancer. Proc Natl Acad Sci USA 2005; 102(21): 7677-82.
[] [PMID: 15890779]
Ng L, Wan T, Chow A, Iyer D, Man J, Chen G. Osteopontin overexpression induced tumor progression and chemoresistance to oxaliplatin through induction of stem-like properties in human colorectal cancer. Stem cells international 2015.2015: 247892.
Poddar NK, Maurya SK, Saxena V. Role of serine proteases and inhibitors in cancer. In: Chakraborti S, Dhalla N, Eds. Proteases in Physiology and PathologySingapore; Springer.
Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M. Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. J Biol Chem 2002; 277(27): 24562-70.
[] [PMID: 11983703]
Borgoño CA, Diamandis EP. The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer 2004; 4(11): 876-90.
[] [PMID: 15516960]
Plendl J, Snyman C, Naidoo S, Sawant S, Mahabeer R, Bhoola KD. Expression of tissue kallikrein and kinin receptors in angiogenic microvascular endothelial cells. Biol Chem 2000; 381(11): 1103-15.
[] [PMID: 11154068]
Adib TR, Henderson S, Perrett C, et al. Predicting biomarkers for ovarian cancer using gene-expression microarrays. Br J Cancer 2004; 90(3): 686-92.
[] [PMID: 14760385]
Heeb MJ, España F. α2-macroglobulin and C1-inactivator are plasma inhibitors of human glandular kallikrein. Blood Cells Mol Dis 1998; 24(4): 412-9.
[] [PMID: 9851894]
Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 2001; 22(2): 184-204.
[PMID: 11294823]
Henttu P, Vihko P. cDNA coding for the entire human prostate specific antigen shows high homologies to the human tissue kallikrein genes. Biochem Biophys Res Commun 1989; 160(2): 903-10.
[] [PMID: 2470373]
Xi Z, Klokk TI, Korkmaz K, et al. Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer. Cancer Res 2004; 64(7): 2365-70.
[] [PMID: 15059887]
Brillard-Bourdet M, Moreau T, Gauthier F. Substrate specificity of tissue kallikreins: importance of an extended interaction site. Biochim Biophys Acta 1995; 1246(1): 47-52.
[] [PMID: 7811730]
Rai PK, Poddar NK. Serine proteases in ovarian cancer.In: Gupta SP, Ed Cancer-Leading Proteases. UK Elsevier 2020; pp. 183-213.
Obiezu CV, Scorilas A, Katsaros D, et al. Higher human kallikrein gene 4 (KLK4) expression indicates poor prognosis of ovarian cancer patients. Clin Cancer Res 2001; 7(8): 2380-6.
[PMID: 11489816]
Oikonomopoulou K, Scorilas A, Michael IP, et al. Kallikreins as markers of disseminated tumour cells in ovarian cancer- a pilot study. Tumour Biol 2006; 27(2): 104-14.
[] [PMID: 16557045]
American Cancer Society. Cancer facts and figures. Society 2008. Available from: https://www.- facts-figures/cancer-facts-figures-2008.
Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987; 317(15): 909-16.
[] [PMID: 2442609]
Hakalahti L, Vihko P, Henttu P, Autio-Harmainen H, Soini Y, Vihko R. Evaluation of PAP and PSA gene expression in prostatic hyperplasia and prostatic carcinoma using northern-blot analyses, in situ hybridization and immunohistochemical stainings with monoclonal and bispecific antibodies. Int J Cancer 1993; 55(4): 590-7.
[] [PMID: 7691762]
Diamandis EP, Scorilas A, Fracchioli S, et al. Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. J Clin Oncol 2003; 21(6): 1035-43.
[] [PMID: 12637468]
Matsuzaki H, Kobayashi H, Yagyu T, et al. Plasma bikunin as a favorable prognostic factor in ovarian cancer. J Clin Oncol 2005; 23(7): 1463-72.
[] [PMID: 15735122]
Bast RC, Urban N, Shridhar V, Smith D, Zhang Z, Skates S, et al. Early detection of ovarian cancer: promise and reality.Ovarian Cancer. Springer 2002; pp. 61-97.
Tanaka Y, Kobayashi H, Suzuki M, et al. Reduced bikunin gene expression as a factor of poor prognosis in ovarian carcinoma. Cancer 2003; 98(2): 424-30.
[] [PMID: 12872365]
Dørum A, Kristensen GB, Abeler VM, Tropé CG, Møller P. Early detection of familial ovarian cancer. Eur J Cancer 1996; 32A(10): 1645-51.
[] [PMID: 8983269]
Colaković S, Lukiç V, Mitroviç L, Jeliç S, Susnjar S, Marinkoviç J. Prognostic value of CA125 kinetics and half-life in advanced ovarian cancer. Int J Biol Markers 2000; 15(2): 147-52.
[] [PMID: 10883888]
Nakae M, Iwamoto I, Fujino T, et al. Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer. J Obstet Gynaecol Res 2006; 32(3): 309-14.
[] [PMID: 16764622]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy