Carbohydrate antigens as potential biomarkers for the malignancy in patients with idiopathic deep venous thrombosis: A retrospective cohort study

Abstract

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, β₂-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (β-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and β₂-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and β₂-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.

Keywords

biomarkers / cancer / deep vein thrombosis / idiopathic deep venous thrombosis / carbohydrate antigen

References

[1] TrousseauA. Phlegmasia Alba Dolens, 18652nd edParis, JB Baillère, 659-712

[2] BillrothT. Lectures on surgical pathology and therapeutics: a handbook for students and practitioners, 18788th edLondon, The New Sydenham Society, 1877-1878

[3] SackGHJr, LevinJ, BellWR. Trousseau’s syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine, 1977, 56(1): 1-37 PMID: 834136

[4] LipGY, ChinBS, BlannAD. Cancer and the prothrombotic state. Lancet Oncol, 2002, 3(1): 27-34 PMID: 11908507

[5] RicklesFR, LevineM, EdwardsRL. Hemostatic alterations in cancer patients. Cancer Metastasis Rev, 1992, 11(3–4): 237-248 PMID: 1423816

[6] KhoranaAA, FrancisCW, CulakovaE, et al. . Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost, 2007, 5(3): 632-634 PMID: 17319909

[7] FalangaA, ZacharskiL. Deep vein thrombosis in cancer: the scale of the problem and approaches to management. Ann Oncol, 2005, 16(5): 696-701 PMID: 15802275

[8] PrandoniP, LensingAW, CogoA, et al. . The long-term clinical course of acute deep vein thrombosis. Ann Intern Med, 1996, 125(1): 1-7 PMID: 8644983

[9] SørensenHT, MellemkjaerL, OlsenJH, et al. . Prognosis of cancer associated with venous thromboembolism. N Engl J Med, 2000, 343(25): 1846-1850 PMID: 11117976

[10] SeddighzadehA, ShettyR, GoldhaberSZ. Venous thromboembolism in patients with active cancer. Thromb Haemost, 2007, 98(3): 656-661 PMID: 17849056

[11] SallahS, WanJY, NguyenNP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost, 2002, 87(4): 575-579 PMID: 12008937

[12] PalaretiG, LegnaniC, CosmiB, et al. . Predictive value of D-dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idiopathic event and in carriers of congenital thrombophilia. Circulation, 2003, 108(3): 313-318 PMID: 12847064

[13] ScatesSM. Diagnosis and treatment of cancer-related thrombosis. Semin Thromb Hemostas, 1992, 18(4): 373-379

[14] FengyuS, ChunyeX, MinoruT, et al. . Detection of carcinoembryonic antigens using a surface plasmon resonance biosensor. Sensors, 2008, 8: 4282-4295

[15] KourisNT, ZacharosID, KontogianniDD, et al. . The significance of CA 125 levels in patients with chronic congestive heart failure. Correlation with clinical and echocardiographic parameters. Eur J Heart Fail, 2005, 7(2): 199-203 PMID: 15701467

[16] SutherlandDE, WeitzIC, LiebmanHA. Thromboembolic complications of cancer: epidemiology, pathogenesis, diagnosis and treatment. Am J Hematol, 2003, 72(1): 43-52 PMID: 12508268

[17] SabaHI, KhalilFK, MorelliGA, et al. . Thromboembolism preceding cancer: a correlation study. Am J Hematol, 2003, 72(2): 109-114 PMID: 12555214

[18] MonrealM, LensingAW, PrinsMH, et al. . Screening for occult cancer in patients with acute deep vein thrombosis or pulmonary embolism. J Thromb Haemost, 2004, 2(6): 876-881 PMID: 15140120

[19] ShitritD, ZingermanB, ShitritAB, et al. . Diagnostic value of CYFRA 21-1, CEA, CA 19-9, CA 15-3, and CA 125 assays in pleural effusions: analysis of 116 cases and review of the literature. Oncologist, 2005, 10(7): 501-507 PMID: 16079317

[20] BilidiricU, CelikyurtU, AcarE, et al. . The value of serum tumour markers in the prediction of aetiology and follow up of patients with pericardial effusion. Cardiovasc J Afr, 2012, 23(3): 143-146

[21] AlbrechtH, CarrawayKL3rd. MUC1 and MUC4: switching the emphasis from large to small. Cancer Biother Radiopharm, 2011, 26(3): 261-271 PMID: 21728842 PMCID: 3128783

[22] HigashiM, YamadaN, YokoyamaS, et al. . Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type. Pathobiology, 2012, 79(2): 101-106 PMID: 22286058

[23] AkagiJ, TakaiE, TamoriY, et al. . CA19-9 epitope a possible marker for MUC-1/Y protein. Int J Oncol, 2001, 18(5): 1085-1091 PMID: 11295060

[24] MalatiT. Tumor markers: An overview. Indian J Clin Biochem, 2007, 22(2): 17-31 PMID: 23105677 PMCID: 3453798

[25] MolinaR, FillellaX, TorresMD, et al. . SCC antigen measured in malignant and nonmalignant disease. Clin Chem, 1990, 36(2): 251-254 PMID: 2302769

[26] OefeleinMG, BrantM, CrottyK. Idiopathic thromboembolism as the presenting sign of occult prostate cancer. Urology, 1998, 51(5): 775-780 PMID: 9610591

[27] HarrisonPM, ArosioP. The ferritins: Molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta, 1996, 1275(3): 161-203 PMID: 8695634

[28] RogersJT, BridgesKR, DurmowiczGP, et al. . Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1. J Biol Chem, 1990, 265(24): 14572-14578 PMID: 1696948

[29] KwakEL, LarochelleDA, BeaumontC, et al. . Role for NF-kappa B in the regulation of ferritin H by tumor necrosis factor-alpha. J Biol Chem, 1995, 270(25): 15285-15293 PMID: 7797515

[30] TsimberidouAM, KantarjianHM, WenS, et al. . The prognostic significance of serum beta2 microglobulin levels in acute myeloid leukemia and prognostic scores predicting survival: analysis of 1,180 patients. Clin Cancer Res, 2008, 14(3): 721-730 PMID: 18245532

[31] MadjdZ, SpendloveI, PinderSE, et al. . Total loss of MHC class I is an independent indicator of good prognosis in breast cancer. Int J Cancer, 2005, 117(2): 248-255 PMID: 15900607

[32] ChronowskiGM, WilderRB, TuckerSL, et al. . An elevated serum -2-microglobulin level is an adverse prognostic factor for overall survival in patients with early stage Hodgkin disease. Cancer, 2002, 95(12): 2534-2538 PMID: 12467067

[33] ParkerTL, StroutMP. Chronic lymphotic leukemia: Prognostic factors and impact on treatment. Discov med, 2011, 11(57): 115-123 PMID: 21356166

[34] GreippPR, DurieBG, WestinJ, et al. . International staging system for multiple myeloma. J Clin Oncol, 2005, 23(15): 3412-3420 PMID: 15809451

[35] BernalM, ConchaA, PaschenA, et al. . Implication of the b2-microglobulin gene in the generation of tumor escape phenotypes. Cancer Immunol Immunother, 2012, 61(9): 1359-1371 PMID: 22833104

[36] KeshengL, HuifengD, XiaowenL. Serum β₂-microglobulin levels in patients with various solid cancer. J Mol Biomark Diagn, 2012, 2: 1-6

[37] XieJ, YiQ. Beta2-microglobulin as a potential initiator of inflammatory responses. Trends in Immuno, 2003, 24(5): 228-229

[38] PoulakisN, SarandakouA, RizosD, et al. . Soluble interleukin-2 receptors and other markers in primary lung cancer. Cancer, 1991, 68(5): 1045-1049 PMID: 1717123

[39] AydinerA, TopuzE, DisciR, et al. . Serum tumor markers for detection of bone metastasis in breasts cancer patients. Acta Oncol, 1994, 33(2): 181-186 PMID: 8204273

[40] TasF, AydinerA, AydinerV, et al. . Clinical usefulness of serum assays of carcinoembryonic antigen and beta 2-microglobulin in the diagnosis and discrimination of metastasis of lung cancer. Turkish Journal of Cancer, 2000, 30: 148-155

[41] MarcillacI, TroalenF, BidatJM, et al. . Free human chorionic gonadotrophin B subunit in gonadal and nongonadal neoplasm. Cancer Res, 1992, 52(14): 3901-3907 PMID: 1377600

[42] SchutgensRE, BeckersMM, HaasFJ, et al. . The predictive value of D-dimer measurement for cancer in patients with deep vein thrombosis. Haematologica, 2005, 90(2): 214-219 PMID: 15710574

[43] SørensenHT, MellemkjaerL, SteffensenFH, et al. . The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N Engl J Med, 1998, 338(17): 1169-1173 PMID: 9554856

[44] LaporteS, TardyB, QuenetS, et al. . The location of deep vein thrombosis as a predictive factor for recurrence and cancer discovery after proximal deep-vein thrombosis. Haematologica, 2003, 88(3): ELT08 PMID: 12651290

[45] BuraA, CailleuxN, BienvenuB, et al. . Incidence and prognosis of cancer associated with bilateral venous thrombosis: a prospective study of 103 patients. J Thromb Haemost, 2004, 2(3): 441-444 PMID: 15009461

[46] MurchisonJT, WylieL, StocktonDL. Excess risk of cancer in patients with primary venous thromboembolism: a national, population-based cohort study. Br J Cancer, 2004, 91(1): 92-95 PMID: 15226761 PMCID: 2364760