Skip to main content
Erschienen in: International Journal of Clinical Oncology 3/2013

01.06.2013 | Original Article

Circulating cell-free human telomerase reverse transcriptase mRNA in plasma and its potential diagnostic and prognostic value for gastric cancer

verfasst von: Yi Kang, Jiancheng Zhang, Peichun Sun, Jia Shang

Erschienen in: International Journal of Clinical Oncology | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

Our aims were to detect circulating cell-free human telomerase reverse transcriptase (hTERT) mRNA in the plasma of gastric cancer patients and evaluate its potential diagnostic and prognostic value.

Methods

Real-time quantitative reverse transcription-polymerase chain reaction was employed to detect circulating cell-free hTERT mRNA from 118 gastric cancer patients, 40 chronic atrophic gastritis (CAG) patients, and 58 healthy controls.

Results

Circulating cell-free hTERT mRNA was detected in all gastric cancer patients, 39 (97.5 %) CAG patients and 56 (96.6 %) healthy control individuals, respectively. However, it was higher in gastric cancer than in CAG and healthy controls (all at P < 0.05). Moreover, its high level was significantly correlated with clinical stages (P < 0.001) and lymph nodes metastasis (P < 0.001). There was no difference between circulating cell-free mRNA and other parameters. The area under the receiver operating characteristic (ROC) curve was 0.891, and the optimal cut-off point was 0.18, providing a sensitivity of 66 % and a specificity of 87 %. The ROC analysis showed that the diagnosis capability of circulating cell-free mRNA was statistically significantly higher than that of carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9), alone [CEA (0.656); CA19-9 (0.722)] or in combination (0.756). Kaplan–Meier analysis demonstrated a correlation between increased circulating cell-free hTERT mRNA and reduced disease-free survival (P < 0.001) and overall survival (P < 0.001). Cox analysis indicated that it was an independent prognostic factor for disease-free survival and overall survival.

Conclusions

We concluded that circulating cell-free hTERT mRNA might serve as a potential and useful noninvasive tumor marker for gastric cancer.
Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRef Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRef
2.
Zurück zum Zitat Menges M (2011) Gastric cancer: Where is the place for the surgeon, the oncologist and the endoscopist today? World J Gastrointest Oncol 3:10–13PubMedCrossRef Menges M (2011) Gastric cancer: Where is the place for the surgeon, the oncologist and the endoscopist today? World J Gastrointest Oncol 3:10–13PubMedCrossRef
3.
Zurück zum Zitat Dilege E, Mihmanli M, Demir U et al (2010) Prognostic value of preoperative CEA and CA19-9 levels in resectable gastric cancer. Hepatogastroenterology 57:674–677PubMed Dilege E, Mihmanli M, Demir U et al (2010) Prognostic value of preoperative CEA and CA19-9 levels in resectable gastric cancer. Hepatogastroenterology 57:674–677PubMed
4.
Zurück zum Zitat Schneider J, Schulze G (2003) Comparison of tumor M2-pyruvate kinase (tumor M2-PK), carcinoembryonic antigen (CEA), carbohydrate antigens CA 19-9 and CA 72-4 in the diagnosis of gastrointestinal cancer. Anticancer Res 23:5089–5093PubMed Schneider J, Schulze G (2003) Comparison of tumor M2-pyruvate kinase (tumor M2-PK), carcinoembryonic antigen (CEA), carbohydrate antigens CA 19-9 and CA 72-4 in the diagnosis of gastrointestinal cancer. Anticancer Res 23:5089–5093PubMed
5.
Zurück zum Zitat Kopreski MS, Benko FA, Kwak LW et al (1999) Detection of tumor messenger RNA in the serum of patients with malignant melanoma. Clin Cancer Res 5:1961–1965PubMed Kopreski MS, Benko FA, Kwak LW et al (1999) Detection of tumor messenger RNA in the serum of patients with malignant melanoma. Clin Cancer Res 5:1961–1965PubMed
6.
Zurück zum Zitat Schwarzenbach H, Hoon DS, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11:426–437PubMedCrossRef Schwarzenbach H, Hoon DS, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11:426–437PubMedCrossRef
7.
Zurück zum Zitat Dasi F, Martinez-Rodes P, March JA et al (2006) Real-time quantification of human telomerase reverse transcriptase mRNA in the plasma of patients with prostate cancer. Ann N Y Acad Sci 1075:204–210PubMedCrossRef Dasi F, Martinez-Rodes P, March JA et al (2006) Real-time quantification of human telomerase reverse transcriptase mRNA in the plasma of patients with prostate cancer. Ann N Y Acad Sci 1075:204–210PubMedCrossRef
8.
Zurück zum Zitat Kudo Y, Ochi T, Shimada H et al (2008) Utility of plasma circulating mRNA as a marker to detect hepatic injury. J Vet Med Sci 70:993–995PubMedCrossRef Kudo Y, Ochi T, Shimada H et al (2008) Utility of plasma circulating mRNA as a marker to detect hepatic injury. J Vet Med Sci 70:993–995PubMedCrossRef
9.
Zurück zum Zitat Takahashi S, Miura N, Harada T et al (2010) Prognostic impact of clinical course-specific mRNA expression profiles in the serum of perioperative patients with esophageal cancer in the ICU: a case control study. J Transl Med 8:103PubMedCrossRef Takahashi S, Miura N, Harada T et al (2010) Prognostic impact of clinical course-specific mRNA expression profiles in the serum of perioperative patients with esophageal cancer in the ICU: a case control study. J Transl Med 8:103PubMedCrossRef
10.
Zurück zum Zitat Garcia V, Garcia JM, Pena C et al (2008) Free circulating mRNA in plasma from breast cancer patients and clinical outcome. Cancer Lett 263:312–320PubMedCrossRef Garcia V, Garcia JM, Pena C et al (2008) Free circulating mRNA in plasma from breast cancer patients and clinical outcome. Cancer Lett 263:312–320PubMedCrossRef
11.
Zurück zum Zitat Garcia V, Garcia JM, Silva J et al (2009) Extracellular tumor-related mRNA in plasma of lymphoma patients and survival implications. PLoS ONE 4:e8173PubMedCrossRef Garcia V, Garcia JM, Silva J et al (2009) Extracellular tumor-related mRNA in plasma of lymphoma patients and survival implications. PLoS ONE 4:e8173PubMedCrossRef
12.
Zurück zum Zitat Nakamura TM, Morin GB, Chapman KB et al (1997) Telomerase catalytic subunit homologs from fission yeast and human. Science 277:955–959PubMedCrossRef Nakamura TM, Morin GB, Chapman KB et al (1997) Telomerase catalytic subunit homologs from fission yeast and human. Science 277:955–959PubMedCrossRef
13.
Zurück zum Zitat Yuan J, Yang BM, Zhong ZH et al (2009) Upregulation of survivin during immortalization of nontransformed human fibroblasts transduced with telomerase reverse transcriptase. Oncogene 28:2678–2689PubMedCrossRef Yuan J, Yang BM, Zhong ZH et al (2009) Upregulation of survivin during immortalization of nontransformed human fibroblasts transduced with telomerase reverse transcriptase. Oncogene 28:2678–2689PubMedCrossRef
14.
Zurück zum Zitat Xu Y, Yu M, Wu F et al (2009) Effects of ectopic expression of human telomerase reverse transcriptase on immortalization of feather keratinocyte stem cells. J Exp Zool B Mol Dev Evol 312:872–884PubMedCrossRef Xu Y, Yu M, Wu F et al (2009) Effects of ectopic expression of human telomerase reverse transcriptase on immortalization of feather keratinocyte stem cells. J Exp Zool B Mol Dev Evol 312:872–884PubMedCrossRef
15.
Zurück zum Zitat Yip YL, Tsang CM, Deng W et al (2010) Expression of Epstein–Barr virus-encoded LMP1 and hTERT extends the life span and immortalizes primary cultures of nasopharyngeal epithelial cells. J Med Virol 82:1711–1723PubMedCrossRef Yip YL, Tsang CM, Deng W et al (2010) Expression of Epstein–Barr virus-encoded LMP1 and hTERT extends the life span and immortalizes primary cultures of nasopharyngeal epithelial cells. J Med Virol 82:1711–1723PubMedCrossRef
16.
Zurück zum Zitat Mai W, Kawakami K, Shakoori A et al (2009) Deregulated GSK3{beta} sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase. Clin Cancer Res 15:6810–6819PubMedCrossRef Mai W, Kawakami K, Shakoori A et al (2009) Deregulated GSK3{beta} sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase. Clin Cancer Res 15:6810–6819PubMedCrossRef
17.
Zurück zum Zitat Suzuki K, Kashimura H, Ohkawa J et al (2000) Expression of human telomerase catalytic subunit gene in cancerous and precancerous gastric conditions. J Gastroenterol Hepatol 15:744–751PubMedCrossRef Suzuki K, Kashimura H, Ohkawa J et al (2000) Expression of human telomerase catalytic subunit gene in cancerous and precancerous gastric conditions. J Gastroenterol Hepatol 15:744–751PubMedCrossRef
18.
Zurück zum Zitat Yoo J, Park SY, Kang SJ et al (2003) Expression of telomerase activity, human telomerase RNA, and telomerase reverse transcriptase in gastric adenocarcinomas. Mod Pathol 16:700–707PubMedCrossRef Yoo J, Park SY, Kang SJ et al (2003) Expression of telomerase activity, human telomerase RNA, and telomerase reverse transcriptase in gastric adenocarcinomas. Mod Pathol 16:700–707PubMedCrossRef
19.
Zurück zum Zitat Wang W, Luo HS, Yu BP (2004) Expression of NF-kappaB and human telomerase reverse transcriptase in gastric cancer and precancerous lesions. World J Gastroenterol 10:177–181PubMed Wang W, Luo HS, Yu BP (2004) Expression of NF-kappaB and human telomerase reverse transcriptase in gastric cancer and precancerous lesions. World J Gastroenterol 10:177–181PubMed
20.
Zurück zum Zitat Gigek CO, Leal MF, Silva PN et al (2009) hTERT methylation and expression in gastric cancer. Biomarkers 14:630–636PubMedCrossRef Gigek CO, Leal MF, Silva PN et al (2009) hTERT methylation and expression in gastric cancer. Biomarkers 14:630–636PubMedCrossRef
21.
Zurück zum Zitat Chen XQ, Bonnefoi H, Pelte MF et al (2000) Telomerase RNA as a detection marker in the serum of breast cancer patients. Clin Cancer Res 6:3823–3826PubMed Chen XQ, Bonnefoi H, Pelte MF et al (2000) Telomerase RNA as a detection marker in the serum of breast cancer patients. Clin Cancer Res 6:3823–3826PubMed
22.
Zurück zum Zitat Miura N, Nakamura H, Sato R et al (2006) Clinical usefulness of serum telomerase reverse transcriptase (hTERT) mRNA and epidermal growth factor receptor (EGFR) mRNA as a novel tumor marker for lung cancer. Cancer Sci 97:1366–1373PubMedCrossRef Miura N, Nakamura H, Sato R et al (2006) Clinical usefulness of serum telomerase reverse transcriptase (hTERT) mRNA and epidermal growth factor receptor (EGFR) mRNA as a novel tumor marker for lung cancer. Cancer Sci 97:1366–1373PubMedCrossRef
23.
Zurück zum Zitat Tani N, Ichikawa D, Ikoma D et al (2007) Circulating cell-free mRNA in plasma as a tumor marker for patients with primary and recurrent gastric cancer. Anticancer Res 27:1207–1212PubMed Tani N, Ichikawa D, Ikoma D et al (2007) Circulating cell-free mRNA in plasma as a tumor marker for patients with primary and recurrent gastric cancer. Anticancer Res 27:1207–1212PubMed
24.
Zurück zum Zitat Miura N, Shiota G, Nakagawa T et al (2003) Sensitive detection of human telomerase reverse transcriptase mRNA in the serum of patients with hepatocellular carcinoma. Oncology 64:430–434PubMedCrossRef Miura N, Shiota G, Nakagawa T et al (2003) Sensitive detection of human telomerase reverse transcriptase mRNA in the serum of patients with hepatocellular carcinoma. Oncology 64:430–434PubMedCrossRef
25.
Zurück zum Zitat Khan FA, Shukla AN (2006) Pathogenesis and treatment of gastric carcinoma: “an up-date with brief review”. J Cancer Res Ther 2:196–199PubMedCrossRef Khan FA, Shukla AN (2006) Pathogenesis and treatment of gastric carcinoma: “an up-date with brief review”. J Cancer Res Ther 2:196–199PubMedCrossRef
26.
Zurück zum Zitat Yang SM, Fang DC, Yang JL et al (2008) Antisense human telomerase reverse transcriptase could partially reverse malignant phenotypes of gastric carcinoma cell line in vitro. Eur J Cancer Prev 17:209–217PubMedCrossRef Yang SM, Fang DC, Yang JL et al (2008) Antisense human telomerase reverse transcriptase could partially reverse malignant phenotypes of gastric carcinoma cell line in vitro. Eur J Cancer Prev 17:209–217PubMedCrossRef
27.
Zurück zum Zitat Ebert MP, Rocken C (2006) Molecular screening of gastric cancer by proteome analysis. Eur J Gastroenterol Hepatol 18:847–853PubMedCrossRef Ebert MP, Rocken C (2006) Molecular screening of gastric cancer by proteome analysis. Eur J Gastroenterol Hepatol 18:847–853PubMedCrossRef
28.
Zurück zum Zitat Oh BK, Kim H, Park YN et al (2008) High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis. Lab Invest 88:144–152PubMedCrossRef Oh BK, Kim H, Park YN et al (2008) High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis. Lab Invest 88:144–152PubMedCrossRef
29.
Zurück zum Zitat Taubert H, Wurl P, Greither T et al (2007) Stem cell-associated genes are extremely poor prognostic factors for soft-tissue sarcoma patients. Oncogene 26:7170–7174PubMedCrossRef Taubert H, Wurl P, Greither T et al (2007) Stem cell-associated genes are extremely poor prognostic factors for soft-tissue sarcoma patients. Oncogene 26:7170–7174PubMedCrossRef
30.
Zurück zum Zitat Chen HH, Yu CH, Wang JT et al (2007) Expression of human telomerase reverse transcriptase (hTERT) protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma in Taiwan. Oral Oncol 43:122–129PubMedCrossRef Chen HH, Yu CH, Wang JT et al (2007) Expression of human telomerase reverse transcriptase (hTERT) protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma in Taiwan. Oral Oncol 43:122–129PubMedCrossRef
31.
Zurück zum Zitat Boldrini L, Pistolesi S, Gisfredi S et al (2006) Telomerase activity and hTERT mRNA expression in glial tumors. Int J Oncol 28:1555–1560PubMed Boldrini L, Pistolesi S, Gisfredi S et al (2006) Telomerase activity and hTERT mRNA expression in glial tumors. Int J Oncol 28:1555–1560PubMed
32.
Zurück zum Zitat Metzger R, Vallbohmer D, Muller-Tidow C et al (2009) Increased human telomerase reverse transcriptase (hTERT) mRNA expression but not telomerase activity is related to survival in curatively resected non-small cell lung cancer. Anticancer Res 29:1157–1162PubMed Metzger R, Vallbohmer D, Muller-Tidow C et al (2009) Increased human telomerase reverse transcriptase (hTERT) mRNA expression but not telomerase activity is related to survival in curatively resected non-small cell lung cancer. Anticancer Res 29:1157–1162PubMed
33.
Zurück zum Zitat Grochola LF, Greither T, Taubert HW et al (2008) Prognostic relevance of hTERT mRNA expression in ductal adenocarcinoma of the pancreas. Neoplasia 10:973–976PubMed Grochola LF, Greither T, Taubert HW et al (2008) Prognostic relevance of hTERT mRNA expression in ductal adenocarcinoma of the pancreas. Neoplasia 10:973–976PubMed
34.
Zurück zum Zitat Kawai J, Kodera Y, Fujiwara M et al (2005) Telomerase activity as prognostic factor in gastrointestinal stromal tumors of the stomach. Hepatogastroenterology 52:959–964PubMed Kawai J, Kodera Y, Fujiwara M et al (2005) Telomerase activity as prognostic factor in gastrointestinal stromal tumors of the stomach. Hepatogastroenterology 52:959–964PubMed
Metadaten
Titel
Circulating cell-free human telomerase reverse transcriptase mRNA in plasma and its potential diagnostic and prognostic value for gastric cancer
verfasst von
Yi Kang
Jiancheng Zhang
Peichun Sun
Jia Shang
Publikationsdatum
01.06.2013
Verlag
Springer Japan
Erschienen in
International Journal of Clinical Oncology / Ausgabe 3/2013
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-012-0405-9

Weitere Artikel der Ausgabe 3/2013

International Journal of Clinical Oncology 3/2013 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.