Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2013

Open Access 01-12-2013 | Research

Clinical utility of measuring expression levels of KAP1, TIMP1 and STC2 in peripheral blood of patients with gastric cancer

Authors: Yuan-Yu Wang, Li Li, Zhong-Sheng Zhao, Hui-Ju Wang

Published in: World Journal of Surgical Oncology | Issue 1/2013

Login to get access

Abstract

Background

We examined preoperative kinesin II-associated protein (KAP1), TIMP metallopeptidase inhibitor 1 (TIMP1) and stanniocalcin 2 (STC2) expression levels in patients with gastric cancers to assess their clinical application for diagnosing and monitoring diseases.

Methods

Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of KAP1, TIMP1, STC2, talin 2 (TLN2), sushi-repeat-containing protein, X-linked 2 (SRPX2) and secreted protein, acidic, cysteine-rich (SPARC) in the patients’ peripheral blood karyocytes. The data were analyzed with receiver operating characteristics (ROC) curves.

Results

A total of 112 patients with gastric cancer, 42 patients with recurrence and 107 healthy volunteers were recruited. There were significant correlations between KAP1, TIMP1 and STC2 levels, and TNM tumor stages and distant metastases. The area under the ROC curves (AUC) of KAP1 was 0.803 ± 0.040 (P = 0.0001), the AUC of TIMP1 was 0.767 ± 0.043 (P = 0.0001) and the AUC of STC2 was 0.769 ± 0.045 (P = 0.0001), thus differentiating preoperative gastric cancer patients from healthy volunteers by ROC curve analysis. The AUC of STC2 was 0.739 ± 0.070 (P = 0.004) and the AUC of KAP1 was 0.418 ± 0.088 (P = 0.319), thus differentiating recurrence of gastric cancer from healthy volunteers by ROC curve analysis. High TIMP1 and STC2 expression levels were suspected to be poor prognostic factors of disease recurrence in patients with gastric cancer.

Conclusions

KAP1, TIMP1 and STC2 expression levels may be potential biomarkers for the screening, diagnosis, prognosis and surveillance of gastric cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Zhan WH, Han FH: Surgical therapy of gastric cancer in china. J Pract Oncol. 2008, 23: 91-93. Zhan WH, Han FH: Surgical therapy of gastric cancer in china. J Pract Oncol. 2008, 23: 91-93.
2.
go back to reference Ghossein RA, Rosai J: Polymerase chain reaction in the detection of micrometastases and circulating tumor cells. Cancer. 1996, 78: 10-16. 10.1002/(SICI)1097-0142(19960701)78:1<10::AID-CNCR3>3.0.CO;2-L.CrossRefPubMed Ghossein RA, Rosai J: Polymerase chain reaction in the detection of micrometastases and circulating tumor cells. Cancer. 1996, 78: 10-16. 10.1002/(SICI)1097-0142(19960701)78:1<10::AID-CNCR3>3.0.CO;2-L.CrossRefPubMed
3.
go back to reference Pelkey TJ, Frierson HF, Bruns DE: Molecular and immunological detection of circulating tumor cells and micrometastases from solid tumors. Clin Chem. 1996, 42: 1369-1381.PubMed Pelkey TJ, Frierson HF, Bruns DE: Molecular and immunological detection of circulating tumor cells and micrometastases from solid tumors. Clin Chem. 1996, 42: 1369-1381.PubMed
4.
go back to reference Marrelli D, Roviello F, De Stefano A, Farnetani M, Garosi L, Messano A, Pinto E: Prognostic significance of CEA, CA 19–9 and CA 72–4 preoperative serum levels in gastric carcinoma. Oncology. 1999, 57: 55-62. 10.1159/000012001.CrossRefPubMed Marrelli D, Roviello F, De Stefano A, Farnetani M, Garosi L, Messano A, Pinto E: Prognostic significance of CEA, CA 19–9 and CA 72–4 preoperative serum levels in gastric carcinoma. Oncology. 1999, 57: 55-62. 10.1159/000012001.CrossRefPubMed
5.
go back to reference Holten-Andersen MN, Hansen U, Brünner N, Nielsen HJ, Illemann M, Nielsen BS: Localization of tissue inhibitor of metalloproteinases 1 (TIMP-1) in human colorectal adenoma and adenocarcinoma. Int J Cancer. 2005, 113: 198-206. 10.1002/ijc.20566.CrossRefPubMed Holten-Andersen MN, Hansen U, Brünner N, Nielsen HJ, Illemann M, Nielsen BS: Localization of tissue inhibitor of metalloproteinases 1 (TIMP-1) in human colorectal adenoma and adenocarcinoma. Int J Cancer. 2005, 113: 198-206. 10.1002/ijc.20566.CrossRefPubMed
6.
go back to reference Bommarito A, Richiusa P, Carissimi E, Pizzolanti G, Rodolico V, Zito G, Criscimanna A, Di Blasi F, Pitrone M, Zerilli M, Amato MC, Spinelli G, Carina V, Modica G, Latteri MA, Galluzzo A, Giordano C: BRAFV600E mutation, TIMP-1 upregulation, and NF-κB activation: closing the loop on the papillary thyroid cancer trilogy. Endocr Relat Cancer. 2011, 18: 669-685. 10.1530/ERC-11-0076.CrossRefPubMed Bommarito A, Richiusa P, Carissimi E, Pizzolanti G, Rodolico V, Zito G, Criscimanna A, Di Blasi F, Pitrone M, Zerilli M, Amato MC, Spinelli G, Carina V, Modica G, Latteri MA, Galluzzo A, Giordano C: BRAFV600E mutation, TIMP-1 upregulation, and NF-κB activation: closing the loop on the papillary thyroid cancer trilogy. Endocr Relat Cancer. 2011, 18: 669-685. 10.1530/ERC-11-0076.CrossRefPubMed
7.
go back to reference Raulic S, Ramos-Valdes Y, DiMattia GE: Stanniocalcin 2 expression is regulated by hormone signalling and negatively affects breast cancer cell viability in vitro. J Endocrinol. 2008, 197: 517-529. 10.1677/JOE-08-0043.CrossRefPubMed Raulic S, Ramos-Valdes Y, DiMattia GE: Stanniocalcin 2 expression is regulated by hormone signalling and negatively affects breast cancer cell viability in vitro. J Endocrinol. 2008, 197: 517-529. 10.1677/JOE-08-0043.CrossRefPubMed
8.
go back to reference Kita Y, Mimori K, Iwatsuki M, Yokobori T, Ieta K, Tanaka F, Ishii H, Okumura H, Natsugoe S, Mori M: STC2: a predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma. Ann Surg Oncol. 2011, 18: 261-272.CrossRefPubMed Kita Y, Mimori K, Iwatsuki M, Yokobori T, Ieta K, Tanaka F, Ishii H, Okumura H, Natsugoe S, Mori M: STC2: a predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma. Ann Surg Oncol. 2011, 18: 261-272.CrossRefPubMed
9.
go back to reference Ieta K, Tanaka F, Yokobori T, Kita Y, Haraguchi N, Mimori K, Kato H, Asao T, Inoue H, Kuwano H, Mori M: Clinicopathological significance of stanniocalcin 2 gene expression in colorectal cancer. Int J Cancer. 2009, 125: 926-931. 10.1002/ijc.24453.CrossRefPubMed Ieta K, Tanaka F, Yokobori T, Kita Y, Haraguchi N, Mimori K, Kato H, Asao T, Inoue H, Kuwano H, Mori M: Clinicopathological significance of stanniocalcin 2 gene expression in colorectal cancer. Int J Cancer. 2009, 125: 926-931. 10.1002/ijc.24453.CrossRefPubMed
10.
go back to reference Yokoe T, Toiyama Y, Okugawa Y, Tanaka K, Ohi M, Inoue Y, Mohri Y, Miki C, Kusunoki M: KAP1 is associated with peritoneal carcinomatosis in gastric cancer. Ann Surg Oncol. 2010, 17: 821-828. 10.1245/s10434-009-0795-8.CrossRefPubMed Yokoe T, Toiyama Y, Okugawa Y, Tanaka K, Ohi M, Inoue Y, Mohri Y, Miki C, Kusunoki M: KAP1 is associated with peritoneal carcinomatosis in gastric cancer. Ann Surg Oncol. 2010, 17: 821-828. 10.1245/s10434-009-0795-8.CrossRefPubMed
11.
go back to reference Wang YY, Ye ZY, Zhao ZS, Tao HQ, Chu YQ: High-level expression of S100A4 correlates with lymph node metastasis and poor prognosis in patients with gastric cancer. Ann Surg Oncol. 2010, 17: 89-97. 10.1245/s10434-009-0722-z.CrossRefPubMed Wang YY, Ye ZY, Zhao ZS, Tao HQ, Chu YQ: High-level expression of S100A4 correlates with lymph node metastasis and poor prognosis in patients with gastric cancer. Ann Surg Oncol. 2010, 17: 89-97. 10.1245/s10434-009-0722-z.CrossRefPubMed
12.
go back to reference Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, Konishi H, Morimura R, Deguchi K, Fujiwara H, Okamoto K, Otsuji E: Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010, 102: 1174-1179. 10.1038/sj.bjc.6605608.PubMedCentralCrossRefPubMed Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, Konishi H, Morimura R, Deguchi K, Fujiwara H, Okamoto K, Otsuji E: Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010, 102: 1174-1179. 10.1038/sj.bjc.6605608.PubMedCentralCrossRefPubMed
13.
go back to reference Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 2007, 57: 43-66. 10.3322/canjclin.57.1.43.CrossRefPubMed Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 2007, 57: 43-66. 10.3322/canjclin.57.1.43.CrossRefPubMed
14.
go back to reference Genta RM: Screening for gastric cancer: does it make sense?. Aliment Pharmacol Ther. 2004, 20: 42-47.CrossRefPubMed Genta RM: Screening for gastric cancer: does it make sense?. Aliment Pharmacol Ther. 2004, 20: 42-47.CrossRefPubMed
15.
go back to reference Marrelli D, Pinto E, De Stefano A, Farnetani M, Garosi L, Roviello F: Clinical utility of CEA, CA 19–9, and CA 72–4 in the follow-up of patients with resectable gastric cancer. Am J Surg. 2001, 181: 16-19. 10.1016/S0002-9610(00)00549-3.CrossRefPubMed Marrelli D, Pinto E, De Stefano A, Farnetani M, Garosi L, Roviello F: Clinical utility of CEA, CA 19–9, and CA 72–4 in the follow-up of patients with resectable gastric cancer. Am J Surg. 2001, 181: 16-19. 10.1016/S0002-9610(00)00549-3.CrossRefPubMed
16.
go back to reference Ishigami S, Natsugoe S, Hokita S, Che X, Tokuda K, Nakajo A, Iwashige H, Tokushige M, Watanabe T, Takao S, Aikou T: Clinical importance of preoperative carcinoembryonic antigen and carbohydrate antigen 19–9 levels in gastric cancer. J Clin Gastroenterol. 2001, 32: 41-44. 10.1097/00004836-200101000-00010.CrossRefPubMed Ishigami S, Natsugoe S, Hokita S, Che X, Tokuda K, Nakajo A, Iwashige H, Tokushige M, Watanabe T, Takao S, Aikou T: Clinical importance of preoperative carcinoembryonic antigen and carbohydrate antigen 19–9 levels in gastric cancer. J Clin Gastroenterol. 2001, 32: 41-44. 10.1097/00004836-200101000-00010.CrossRefPubMed
17.
go back to reference Gaspar MJ, Arribas I, Coca MC, Díez-Alonso M: Prognostic value of carcinoembryonic antigen, CA 19–9 and CA 72–4 in gastric carcinoma. Tumour Biol. 2001, 22: 318-322. 10.1159/000050633.CrossRefPubMed Gaspar MJ, Arribas I, Coca MC, Díez-Alonso M: Prognostic value of carcinoembryonic antigen, CA 19–9 and CA 72–4 in gastric carcinoma. Tumour Biol. 2001, 22: 318-322. 10.1159/000050633.CrossRefPubMed
18.
go back to reference O’Sullivan GC, Collins JK, Kelly J, Morgan J, Madden M, Shanahan F: Micrometastases: marker of metastatic potential or evidence of residual disease?. Gut. 1997, 40: 512-515.PubMedCentralCrossRefPubMed O’Sullivan GC, Collins JK, Kelly J, Morgan J, Madden M, Shanahan F: Micrometastases: marker of metastatic potential or evidence of residual disease?. Gut. 1997, 40: 512-515.PubMedCentralCrossRefPubMed
19.
go back to reference Jeffery N, McLean MH, El-Omar EM, Murray GI: The matrix metalloproteinase/tissue inhibitor of matrix metalloproteinase profile in colorectal polyp cancers. Histopathology. 2009, 54: 820-828. 10.1111/j.1365-2559.2009.03301.x.CrossRefPubMed Jeffery N, McLean MH, El-Omar EM, Murray GI: The matrix metalloproteinase/tissue inhibitor of matrix metalloproteinase profile in colorectal polyp cancers. Histopathology. 2009, 54: 820-828. 10.1111/j.1365-2559.2009.03301.x.CrossRefPubMed
20.
go back to reference Varghese S, Burness M, Xu H, Beresnev T, Pingpank J, Alexander HR: Site-specific gene expression profiles and novel molecular prognostic factors in patients with lower gastrointestinal adenocarcinoma diffusely metastatic to liver or peritoneum. Ann Surg Oncol. 2007, 14: 3460-3471. 10.1245/s10434-007-9557-7.CrossRefPubMed Varghese S, Burness M, Xu H, Beresnev T, Pingpank J, Alexander HR: Site-specific gene expression profiles and novel molecular prognostic factors in patients with lower gastrointestinal adenocarcinoma diffusely metastatic to liver or peritoneum. Ann Surg Oncol. 2007, 14: 3460-3471. 10.1245/s10434-007-9557-7.CrossRefPubMed
21.
go back to reference Kebebew E, Peng M, Reiff E, McMillan A: Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer. 2006, 106: 2592-2597. 10.1002/cncr.21922.CrossRefPubMed Kebebew E, Peng M, Reiff E, McMillan A: Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer. 2006, 106: 2592-2597. 10.1002/cncr.21922.CrossRefPubMed
22.
go back to reference Yoshino Y, Kageshita T, Nakajima M, Funakubo M, Ihn H: Clinical relevance of serum levels of matrix metallopeptidase-2, and tissue inhibitor of metalloproteinase-1 and −2 in patients with malignant melanoma. J Dermatol. 2008, 35: 206-214. 10.1111/j.1346-8138.2008.00446.x.CrossRefPubMed Yoshino Y, Kageshita T, Nakajima M, Funakubo M, Ihn H: Clinical relevance of serum levels of matrix metallopeptidase-2, and tissue inhibitor of metalloproteinase-1 and −2 in patients with malignant melanoma. J Dermatol. 2008, 35: 206-214. 10.1111/j.1346-8138.2008.00446.x.CrossRefPubMed
23.
go back to reference Law AY, Wong CK: Stanniocalcin-2 is a HIF-1 target gene that promotes cell proliferation in hypoxia. Exp Cell Res. 2010, 316: 466-476. 10.1016/j.yexcr.2009.09.018.CrossRefPubMed Law AY, Wong CK: Stanniocalcin-2 is a HIF-1 target gene that promotes cell proliferation in hypoxia. Exp Cell Res. 2010, 316: 466-476. 10.1016/j.yexcr.2009.09.018.CrossRefPubMed
24.
go back to reference Law AY, Wong CK: Stanniocalcin-2 promotes epithelial-mesenchymal transition and invasiveness in hypoxic human ovarian cancer cells. Exp Cell Res. 2010, 316: 3425-3434. 10.1016/j.yexcr.2010.06.026.CrossRefPubMed Law AY, Wong CK: Stanniocalcin-2 promotes epithelial-mesenchymal transition and invasiveness in hypoxic human ovarian cancer cells. Exp Cell Res. 2010, 316: 3425-3434. 10.1016/j.yexcr.2010.06.026.CrossRefPubMed
25.
go back to reference Meyer HA, Tölle A, Jung M, Fritzsche FR, Haendler B, Kristiansen I, Gaspert A, Johannsen M, Jung K, Kristiansen G: Identification of stanniocalcin 2 as prognostic marker in renal cell carcinoma. Eur Urol. 2009, 55: 669-678. 10.1016/j.eururo.2008.04.001.CrossRefPubMed Meyer HA, Tölle A, Jung M, Fritzsche FR, Haendler B, Kristiansen I, Gaspert A, Johannsen M, Jung K, Kristiansen G: Identification of stanniocalcin 2 as prognostic marker in renal cell carcinoma. Eur Urol. 2009, 55: 669-678. 10.1016/j.eururo.2008.04.001.CrossRefPubMed
26.
go back to reference Esseghir S, Kennedy A, Seedhar P, Nerurkar A, Poulsom R, Reis-Filho JS, Isacke CM: Identification of NTN4, TRA1, and STC2 as prognostic markers in breast cancer in a screen for signal sequence encoding proteins. Clin Cancer Res. 2007, 13: 3164-3173. 10.1158/1078-0432.CCR-07-0224.CrossRefPubMed Esseghir S, Kennedy A, Seedhar P, Nerurkar A, Poulsom R, Reis-Filho JS, Isacke CM: Identification of NTN4, TRA1, and STC2 as prognostic markers in breast cancer in a screen for signal sequence encoding proteins. Clin Cancer Res. 2007, 13: 3164-3173. 10.1158/1078-0432.CCR-07-0224.CrossRefPubMed
27.
go back to reference Wang C, Rauscher FJ, Cress WD, Chen J: Regulation of E2F1 function by the nuclear corepressor KAP1. J Biol Chem. 2007, 282: 29902-29909. 10.1074/jbc.M704757200.CrossRefPubMed Wang C, Rauscher FJ, Cress WD, Chen J: Regulation of E2F1 function by the nuclear corepressor KAP1. J Biol Chem. 2007, 282: 29902-29909. 10.1074/jbc.M704757200.CrossRefPubMed
28.
go back to reference Tanaka K, Arao T, Maegawa M, Matsumoto K, Kaneda H, Kudo K, Fujita Y, Yokote H, Yanagihara K, Yamada Y, Okamoto I, Nakagawa K, Nishio K: SRPX2 is overexpressed in gastric cancer and promotes cellular migration and adhesion. Int J Cancer. 2009, 124: 1072-1080. 10.1002/ijc.24065.CrossRefPubMed Tanaka K, Arao T, Maegawa M, Matsumoto K, Kaneda H, Kudo K, Fujita Y, Yokote H, Yanagihara K, Yamada Y, Okamoto I, Nakagawa K, Nishio K: SRPX2 is overexpressed in gastric cancer and promotes cellular migration and adhesion. Int J Cancer. 2009, 124: 1072-1080. 10.1002/ijc.24065.CrossRefPubMed
29.
go back to reference Wang L, Yang M, Shan L, Qi L, Chai C, Zhou Q, Yao K, Wu H, Sun W: The role of SPARC protein expression in the progress of gastric cancer. Pathol Oncol Res. 2012, 18: 697-702. 10.1007/s12253-012-9497-9.PubMedCentralCrossRefPubMed Wang L, Yang M, Shan L, Qi L, Chai C, Zhou Q, Yao K, Wu H, Sun W: The role of SPARC protein expression in the progress of gastric cancer. Pathol Oncol Res. 2012, 18: 697-702. 10.1007/s12253-012-9497-9.PubMedCentralCrossRefPubMed
30.
go back to reference Zhao ZS, Wang YY, Chu YQ, Ye ZY, Tao HQ: SPARC is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res. 2010, 16: 260-268. 10.1158/1078-0432.CCR-09-1247.CrossRefPubMed Zhao ZS, Wang YY, Chu YQ, Ye ZY, Tao HQ: SPARC is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res. 2010, 16: 260-268. 10.1158/1078-0432.CCR-09-1247.CrossRefPubMed
31.
go back to reference Haakensen VD, Bjøro T, Lüders T, Riis M, Bukholm IK, Kristensen VN, Troester MA, Homen MM, Ursin G, Børresen-Dale AL, Helland Å: Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas. BMC Cancer. 2011, 11: 332-10.1186/1471-2407-11-332.PubMedCentralCrossRefPubMed Haakensen VD, Bjøro T, Lüders T, Riis M, Bukholm IK, Kristensen VN, Troester MA, Homen MM, Ursin G, Børresen-Dale AL, Helland Å: Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas. BMC Cancer. 2011, 11: 332-10.1186/1471-2407-11-332.PubMedCentralCrossRefPubMed
Metadata
Title
Clinical utility of measuring expression levels of KAP1, TIMP1 and STC2 in peripheral blood of patients with gastric cancer
Authors
Yuan-Yu Wang
Li Li
Zhong-Sheng Zhao
Hui-Ju Wang
Publication date
01-12-2013
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2013
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-11-81

Other articles of this Issue 1/2013

World Journal of Surgical Oncology 1/2013 Go to the issue