Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2013

Open Access 01-12-2013 | Research

Correlation of hK6 expression with tumor recurrence and prognosis in advanced gastric cancer

Authors: Xunqi Liu, Hailin Xiong, Jun Li, Ying He, Xia Yuan

Published in: Diagnostic Pathology | Issue 1/2013

Login to get access

Abstract

Background

Human kallikrein gene 6 (KLK6) is a member of the human kallikrein gene family (Kallikreins, KLKs). Human kallikrein-related peptidase 6 (hK6) is a trypsin-like serine protease encoded by the KLK6, has been reported to be highly expressed in several cancers including gastric cancer. In this study, we investigated the the correlation of hK6 expression with clinicopathological characteristics, tumor recurrence and prognosis in advanced gastric carcinoma after curative resection.

Methods

We retrospectively analyzed the clinical data of 129 cases advanced gastric cancer after curative gastrectomy. The expression of hK6 in advanced gastric cancer tissues compared to adjacent noncancerous tissues were examined, and the relationship between hK6 expression and clinicopathological characteristics was evaluated. In additional, these patients were followed up to investigate the relationship between hK6 expression and the survival time.

Results

The positive rate of hK6 expression was significantly higher in advanced gastric cancer tissue, than that in adjacent noncancerous and gastric ulcer tissues (36.5%, 33.3%, respectively, P < 0.001). There was a close relationship between hK6 expression and TNM stage (P = 0.005), vascular invasion (P = 0.037) and perineural invasion (P = 0.035). Furthermore, patients with hK6 positive showed significantly higher recurrence and poorer prognosis than those with hK6 negative. Multivariate analysis showed that hK6 expression was a significant independent factor for tumor recurrence and overall survival.

Conclusion

hK6 is overexpressed in advanced gastric cancer tissues. Its clinical utility may be used as an unfavorable indicator in predicting tumor recurrence and prognosis for advanced gastric cancer after operation. This study also suggests that hK6 might be a potential therapeutic target for gastric cancer.

Virtual slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​8558403578787206​
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed
2.
Sotiropoulou G, Pampalakis G, Diamandis EP: Functional roles of human kallikrein related peptidases. Biol Chem. 2009, 284: 32989-32994. 10.1074/jbc.R109.027946.CrossRef
3.
Anisowicz A, Sotiropoulou G, Stenman G, Mok SC, Sager R: A novel protease homolog differentially expressed in breast and ovarian cancer. Mol Med. 1996, 2: 624-636.PubMedCentralPubMed
4.
Little SP, Dixon EP, Norris F, Buckley W, Becker GW, Johnson M, Dobbins JR, Wyrick T, Miller JR, MacKellar W: Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer’s disease brain. J Biol Chem. 1997, 272: 25135-25142. 10.1074/jbc.272.40.25135.CrossRefPubMed
5.
Yamashiro K, Tsuruoka N, Kodama S, Tsujimoto M, Yamamura Y, Tanaka T, Nakazato H, Yamaguchi N: Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain. Biochim Biophys Acta. 1997, 1350: 11-14. 10.1016/S0167-4781(96)00187-X.CrossRefPubMed
6.
Nagahara H, Mimofi K, Utsunomiya T, Barnard GF, Ohira M, Hirakawa K, Mori M: Clinicopathologic and biological significance of kallikrein 6 overexpression in human gastric cancer. Clin Cancer Res. 2005, 11: 6800-6806. 10.1158/1078-0432.CCR-05-0943.CrossRefPubMed
7.
Edge SB, Byrd DR, Compton CC: AJCC cancer staging manual. 2009, New York: Springer-Verlag, 117-126. 7
8.
Maniwa Y, Nishio W, Okita Y, Yoshimura M: Expression of nectin 3: Novel prognostic marker of lung adenocarcinoma. Thoracic Cancer. 2012, 3: 175-181. 10.1111/j.1759-7714.2011.00104.x.CrossRef
9.
Sotoudeh K, Hashemi F, Madjd Z, Sadeghipour A, Molanaei S, Kalantary E: The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays. Diagn Pathol. 2012, 7: 57-10.1186/1746-1596-7-57.PubMedCentralCrossRefPubMed
10.
Ambrogi V, Mineo TC: Clinical and biologic prognostic factors in malignant pleural mesothelioma. Thoracic Cancerl. 2012, 3: 289-302. 10.1111/j.1759-7714.2012.00127.x.CrossRef
11.
Ghosh MC, Grass L, Soosaipillai A, Sotiropoulou G, Diamandis EP: Human kallikrein 6 degrades extracellular matrix proteins and may enhance the metastatic potential of tumor cells. Tumor Biol. 2004, 25: 193-199. 10.1159/000081102.CrossRef
12.
Henkhaus RS, Roy UK, Cavallo-Medved D, Sloane BF, Gerner EW, Ignatenko NA: Caveolin-1-mediated expression and secretion of kallikrein 6 in colon cancer cells. Neoplasia. 2008, 10: 140-148. 10.1593/neo.07817.PubMedCentralCrossRefPubMed
13.
Klucky B, MueUer R, Vogt I, Teurich S, Hartenstein B, Breuhahn K, Flechtenmacher C, Angel P, Hess J: Kallikrein 6 induce E-cadherin shedding and promotes cell proliferation, migration, and invasion. Cancer Res. 2007, 67: 8198-8206. 10.1158/0008-5472.CAN-07-0607.CrossRefPubMed
14.
Shan SJ, Scorilas A, Katsaros D, Diamandis EP: Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects. Br J Cancer. 2007, 96: 362-372. 10.1038/sj.bjc.6603556.PubMedCentralCrossRefPubMed
15.
Santin AD, Diamandis EP, Bellone S, Soosaipillai A, Cane S, Palmieri M, Burnett A, Roman JJ, Pecorelli S: Human kallikrein6: a new potential serum biomarker for uterine serous papillary cancer. Clin Cancer Res. 2005, 11: 3320-3325. 10.1158/1078-0432.CCR-04-2528.CrossRefPubMed
16.
Ogawa K, Utsunomiya T, Mimori K, Tanaka F, Inoue H, Nagahara H, Murayama S, Mori M: Clinical significance of human kallikrein gene 6 messenger RNA expression in colorectal cancer. Clin Cancer Res. 2005, 11: 2889-2893. 10.1158/1078-0432.CCR-04-2281.CrossRefPubMed
17.
Yousef GM, Borgoño CA, White NM, Robb JD, Michael IP, Oikonomopoulou K, Khan S, Diamandis EP: In silico analysis of the human kallikrein gene6. Tumour Biol. 2004, 25: 282-289. 10.1159/000081393.CrossRefPubMed
18.
Darling MR, Jackson-Boeters L, Daley TD, Diamandis EP: Human kallikrein 6 expression in salivary gland tumors. J Histochem Cytochem. 2006, 54: 337-342. 10.1369/jhc.5A6803.2005.CrossRefPubMed
19.
White NM, Bui A, Mejia-Guerrero S, Chao J, Soosaipillai A, Youssef Y, Mankaruos M, Honey RJ, Stewart R, Pace KT, Sugar L, Diamandis EP, Doré J, Yousef GM: Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs. Biol Chem. 2010, 391: 411-423.CrossRefPubMed
20.
Spano D, Zollo M: Tumor microenvironment: a main actor in the metastasis process. Clin Exp Metastasis. 2012, 29: 381-395. 10.1007/s10585-012-9457-5.CrossRefPubMed
21.
Pampalakis G, Prosnikli E, Agalioti T, Vlahou A, Zoumpourlis V, Sotiropoulou G: A tumor-protective role for human kallikrein related peptidase 6 in breast cancer mediated by inhibition of epithelial to mesenchymal transition. Cancer Res. 2009, 69: 3779-3787. 10.1158/0008-5472.CAN-08-1976.CrossRefPubMed
22.
Yousef GM, Borgoño CA, Popalis C, Yacoub GM, Polymeris ME, Soosaipillai A, Diamandis EP: In-silico analysis of kallikrein gene expression in pancreatic and colon cancers. Anticancer Res. 2004, 24: 43-51.PubMed
23.
Kim JJ, Kim JT, Yoon HR, Kang MA, Kim JH, Lee YH, Kim JW, Lee SJ, Song EY, Myung PK, Lee HG: Upregulation and secretion of kallikrein-related peptidase 6 (KLK6) in gastric cancer. Tumour Biol. 2012, 33: 731-738. 10.1007/s13277-011-0267-1.CrossRefPubMed
24.
Paliouras M, Borgono C, Diamandis EP: Human tissue kallikreins:the cancer biomarker family. Cancer Lett. 2007, 249: 61-79. 10.1016/j.canlet.2006.12.018.CrossRefPubMed
25.
Lilja H, Ulmert D, Vickers AJ: Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer. 2008, 8: 268-278. 10.1038/nrc2351.CrossRefPubMed
26.
Kountourakis P, Psyrri A, Scorilas A, Camp R, Markakis S, Kowalski D, Diamandis EP, Dimopoulos MA: Prognostic value of kallikrein-related peptidase 6 protein expression levels in advanced ovarian cancer evaluated by automated quantitative analysis (AQUA). Cancer Sci. 2008, 99: 2224-2229. 10.1111/j.1349-7006.2008.00942.x.CrossRefPubMed
27.
Petraki C, Dubinski W, Scorilas A, Saleh C, Pasic MD, Komborozos V, Khalil B, Gabril MY, Streutker C, Diamandis EP, Yousef GM: Evaluation and prognostic significance of human tissue kallikrein-related peptidase 6(KLK6) in colorectal cancer. Pathol Res Pract. 2012, 208: 104-108. 10.1016/j.prp.2011.12.010.CrossRefPubMed
28.
Rückert F, Hennig M, Petraki CD, Wehrum D, Distler M, Denz A, Schröder M, Dawelbait G, Kalthoff H, Saeger HD: Co-expression of KLK6 and KLK10 as prognostic factors for survival in pancreatic ductal adenocarcinoma. Br J Cancer. 2008, 99: 1484-1492. 10.1038/sj.bjc.6604717.PubMedCentralCrossRefPubMed
29.
Nathalie HV, Chris P, Serge G, Catherine C, Benjamin B, Claire B, Christelle P, Briollais L, Pascale R, Marie-Lise J, Yves C: High kallikrein-related peptidase 6 in non-small cell lung cancer cells: an indicator of tumor proliferation and poor prognosis. J Cell Mol Med. 2009, 13: 4014-4022. 10.1111/j.1582-4934.2009.00763.x.PubMedCentralCrossRefPubMed
30.
Talieri M, Zoma M, Devetzi M, Scorilas A, Ardavanis A: Kallikrein-related peptidase 6 (KLK6) gene expression in intracranial tumors. Tumour Biol. 2012, 33: 1375-1383. 10.1007/s13277-012-0385-4.CrossRefPubMed
31.
White NM, Mathews M, Yousef GM, Prizada A, Popadiuk C, Doré JJ: KLK6 and KLK13 predict tumor recurrence in epithelial ovarian carcinoma. Br J Cancer. 2009, 101: 1107-1113. 10.1038/sj.bjc.6605280.PubMedCentralCrossRefPubMed
32.
Kim JT, Song EY, Chung KS, Kang MA, Kim JW, Kim SJ, Yeom YI, Kim JH, Kim KH, Lee HG: Up-regulation and clinical significance of serine protease kallikrein 6 in colon cancer. Cancer. 2011, 17: 2608-2619.CrossRef
33.
Jin J, Jin T, Quan M, Piao Y, Lin Z: Ezrin overexpression predicts the poor prognosis of gastric adenocarcinoma. Diagn Pathol. 2012, 7: 135-10.1186/1746-1596-7-135.PubMedCentralCrossRefPubMed
34.
Metadata
Title
Correlation of hK6 expression with tumor recurrence and prognosis in advanced gastric cancer
Authors
Xunqi Liu
Hailin Xiong
Jun Li
Ying He
Xia Yuan
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-8-62

Other articles of this Issue 1/2013

Diagnostic Pathology 1/2013 Go to the issue

Research

Molecular characterization of Tunisian families with abetalipoproteinemia and identification of a novel mutation in MTTP gene

Research

RETRACTED ARTICLE: Astragalus saponins affect proliferation, invasion and apoptosis of gastric cancer BGC-823 cells

Research

Immunophenotypic features and t(14;18) (q32;q21) translocation of Chinese follicular lymphomas helps to distinguish subgroups

Research

An analysis of Cyclin D1, Cytokeratin 5/6 and Cytokeratin 8/18 expression in breast papillomas and papillary carcinomas

Case Report

Diagnostic dilemma: late presentation of amelanotic BRAF-negative metastatic malignant melanoma resembling clear cell sarcoma – a case report

Software

Analyzing huge pathology images with open source software