title: Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer.
abstract: OBJECTIVE
  To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis.
  
  
  METHODS
  Serum cancer antigens (CA)199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre- and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors.
  
  
  RESULTS
  Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non-recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors.
  
  
  CONCLUSIONS
  CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers.
authors.affiliation: Yun-Feng Wang, Zhi-Hai Peng, Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Yun-Feng Wang, Zhi-Hai Peng, Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: Fei-Ling
authors.initials: FL
authors.lastname: Feng
authors.affiliation: Yun-Feng Wang, Zhi-Hai Peng, Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: Xu-Hong
authors.initials: XH
authors.lastname: Zhao
authors.affiliation: Yun-Feng Wang, Zhi-Hai Peng, Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: Zhen-Xiong
authors.initials: ZX
authors.lastname: Ye
authors.affiliation: Yun-Feng Wang, Zhi-Hai Peng, Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Zeng
authors.affiliation: Yun-Feng Wang, Zhi-Hai Peng, Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Yun-Feng Wang, Zhi-Hai Peng, Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Jiang
authors.affiliation: Yun-Feng Wang, Zhi-Hai Peng, Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China.
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Peng
mesh_terms: D000328:Adult; D000368:Aged; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D005260:Female; D005705:Gallbladder Diseases / Q000097:blood*; D005706:Gallbladder Neoplasms / Q000097:blood* / Q000175:diagnosis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; C074601:CA 242 antigen; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; C578959:carbohydrate antigen 199, human
keywords: Combined detection; Diagnosis; Gallbladder cancer; Prognosis; Tumor marker
references.citation: PLoS One. 2012;7(12):e51513
references.pmid: 23300551
references.citation: Asian Pac J Cancer Prev. 2012;13(4):1317-20
references.pmid: 22799325
references.citation: J Korean Surg Soc. 2013 Mar;84(3):168-77
references.pmid: 23487246
references.citation: Oncologist. 2012;17(12):1504-7
references.pmid: 23220842
references.citation: Asian Pac J Cancer Prev. 2012;13(6):2511-4
references.pmid: 22938413
references.citation: Ann Surg Oncol. 2014 Feb;21(2):449-57
references.pmid: 24081806
references.citation: Med Pregl. 1993;46 Suppl 1:58-9
references.pmid: 8569609
references.citation: World J Surg Oncol. 2012 Oct 27;10:224
references.pmid: 23101681
references.citation: Saudi J Gastroenterol. 2013 Jan-Feb;19(1):34-9
references.pmid: 23319036
references.citation: Asian Pac J Cancer Prev. 2012;13(2):725-9
references.pmid: 22524851
references.citation: N Am J Med Sci. 2012 Oct;4(10):435-41
references.pmid: 23112962
references.citation: Trop Gastroenterol. 2001 Oct-Dec;22(4):227-9
references.pmid: 11963335
references.citation: HPB (Oxford). 2012 Dec;14(12):805-11
references.pmid: 23134181
references.citation: Trop Gastroenterol. 2006 Oct-Dec;27(4):160-5
references.pmid: 17542293
references.citation: J Gastrointest Cancer. 2012 Jun;43(2):267-71
references.pmid: 21573879
references.citation: Onco Targets Ther. 2013 Nov 11;6:1625-30
references.pmid: 24250228
references.citation: World J Gastroenterol. 2008 Nov 21;14(43):6699-703
references.pmid: 19034974
references.citation: Gastrointest Cancer Res. 2013 Jul;6(4):101-5
references.pmid: 24147157
references.citation: Oncol Rep. 2012 Nov;28(5):1531-6
references.pmid: 22895597
references.citation: Hepatogastroenterology. 2013 Sep;60(126):1297-301
references.pmid: 23933921
references.citation: PLoS One. 2012;7(9):e45290
references.pmid: 22984631
references.citation: Pathobiology. 2012;79(2):101-6
references.pmid: 22286058
references.citation: Am Surg. 2010 Nov;76(11):1210-3
references.pmid: 21140686
references.citation: Cancer Cell Int. 2013 Jun 26;13(1):64
references.pmid: 23802572
references.citation: Biotechnol Lett. 2012 Jul;34(7):1235-41
references.pmid: 22456901
references.citation: World J Gastroenterol. 2009 Sep 14;15(34):4240-62
references.pmid: 19750567
references.citation: Clin Epigenetics. 2012 Jul 13;4(1):11
references.pmid: 22794276
references.citation: World J Gastroenterol. 2010 Dec 21;16(47):5965-74
references.pmid: 21157973
references.citation: J Surg Oncol. 2006 Jun 15;93(8):665-9
references.pmid: 16724349
references.citation: Arch Iran Med. 2013 Nov;16(11):631-5
references.pmid: 24206403
references.citation: World J Gastroenterol. 2009 Dec 21;15(47):5976-82
references.pmid: 20014463
references.citation: Hepatobiliary Pancreat Dis Int. 2013 Apr;12(2):189-95
references.pmid: 23558074
references.citation: Oncoimmunology. 2013 Jul 1;2(7):e24882
references.pmid: 24073370
references.citation: Biomarkers. 2013 Feb;18(1):1-9
references.pmid: 22931385
references.citation: J Dig Dis. 2013 Jan;14(1):45-50
references.pmid: 23134201
references.citation: Clin Lab. 2012;58(1-2):97-105
references.pmid: 22372351
references.citation: Chin Med J (Engl). 2013 Aug;126(16):3044-7
references.pmid: 23981609
references.citation: BMC Gastroenterol. 2013 May 14;13:87
references.pmid: 23672279