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Published in: International Journal of Clinical Oncology 6/2011

01-12-2011 | Original Article

Serum human telomerase reverse transcriptase: a novel biomarker for breast cancer diagnosis

Authors: Mahendar Porika, Radhika Tippani, Sekhar R. Bollam, Sree Divya Panuganti, Christopher Thamidala, Sadanandam Abbagani

Published in: International Journal of Clinical Oncology | Issue 6/2011

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Abstract

Background

Telomerase is a ribonucleoprotein complex composed mainly of a reverse transcriptase catalytic subunit, telomerase reverse transcriptase (hTERT). Expression of hTERT confers telomerase activity, indicating that hTERT is the rate-limiting component of human telomerase. The aim of the present study was to investigate the diagnostic implications of hTERT in the serum of breast cancer patients.

Methods

The study was conducted on 159 breast cancer patients and 41 healthy volunteers as controls. The evaluation of hTERT, cancer antigen 15.3 and carcinoembryonic antigen were performed by enzyme-linked immunosorbent assay, and analysed for their correlation with the patient’s clinicopathological features.

Results

27 of 52 (51.9%) patients with stage I breast cancer, 31 of 40 (77.5%) with stage II and 30 of 34 (88.2%) patients with stage III exhibited elevated hTERT levels. Serum hTERT levels showed significantly higher mean values in patients with breast cancer than healthy individuals. The sensitivity and specificity of hTERT in cancer diagnosis was 68.9 and 83.3%, respectively, which is significantly higher than conventional markers. The expression of serum hTERT was significantly correlated with telomerase activity in breast cancer tissues. Pretreatment serum hTERT levels showed a significant correlation with clinical stage, while correlation with nodal status and tumor size were marginal and no correlation was found with family history and age.

Conclusion

Serum hTERT is useful for diagnosing and assessing the clinical stage of breast cancer and is superior to conventional markers. Therefore, serum hTERT could have a potential application as a novel biomarker for breast cancer diagnosis.
Literature
1.
go back to reference Umi MAH, Louise R, Radka S et al (2008) A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression. Glycobiology 18:1105–1118CrossRef Umi MAH, Louise R, Radka S et al (2008) A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression. Glycobiology 18:1105–1118CrossRef
2.
go back to reference Yeole BB, Kumar AVR, Kurkure A et al (2004) Population based survival from cancers of breast, cervix and ovary in women in Mumbai, India. Asian Pac J Cancer Prev 5:308–315PubMed Yeole BB, Kumar AVR, Kurkure A et al (2004) Population based survival from cancers of breast, cervix and ovary in women in Mumbai, India. Asian Pac J Cancer Prev 5:308–315PubMed
3.
go back to reference Chatterjee SK, Zetter BR (2005) Cancer biomarkers: knowing the present and predicting the future. Future Oncol 1:37–50PubMedCrossRef Chatterjee SK, Zetter BR (2005) Cancer biomarkers: knowing the present and predicting the future. Future Oncol 1:37–50PubMedCrossRef
4.
go back to reference Mahendar P, Nagulu M, Uday Kiran V et al (2010) Evaluation of tumor markers in southern Indian breast cancer patients. Asian Pac J Cancer Prev 11:157–159 Mahendar P, Nagulu M, Uday Kiran V et al (2010) Evaluation of tumor markers in southern Indian breast cancer patients. Asian Pac J Cancer Prev 11:157–159
5.
go back to reference Duffy MJ (2006) Serum tumor markers in breast cancer: are they of clinical value? Clin Chem 52:345–351PubMedCrossRef Duffy MJ (2006) Serum tumor markers in breast cancer: are they of clinical value? Clin Chem 52:345–351PubMedCrossRef
8.
go back to reference Shay JW, Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer 33:787–791PubMedCrossRef Shay JW, Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer 33:787–791PubMedCrossRef
9.
go back to reference Mahendar P, Uday Kiran V, Radhika K et al (2009) Detection of telomerase activity in different cancer tissues: early detection. Curr Trends Biotechnol Pharmacy 3:105–110 Mahendar P, Uday Kiran V, Radhika K et al (2009) Detection of telomerase activity in different cancer tissues: early detection. Curr Trends Biotechnol Pharmacy 3:105–110
10.
go back to reference Cairney CJ, Keth WN (2008) Telomerase redefined: Integrated regulation of hTR and hTERT for telomere maintenance and telomerase activity. Biochimie 90:13–23PubMedCrossRef Cairney CJ, Keth WN (2008) Telomerase redefined: Integrated regulation of hTR and hTERT for telomere maintenance and telomerase activity. Biochimie 90:13–23PubMedCrossRef
12.
go back to reference Wu A, Ichihashi M, Ueda M (1999) Correlation of the expression of human telomerase subunits with telomerase activity in normal skin and skin tumors. Cancer 86:2038–2044PubMedCrossRef Wu A, Ichihashi M, Ueda M (1999) Correlation of the expression of human telomerase subunits with telomerase activity in normal skin and skin tumors. Cancer 86:2038–2044PubMedCrossRef
13.
go back to reference Bachand F, Triki I, Autexier C (2001) Human telomerase RNA–protein interactions. Nucleic Acids Res 29:3385–3393PubMedCrossRef Bachand F, Triki I, Autexier C (2001) Human telomerase RNA–protein interactions. Nucleic Acids Res 29:3385–3393PubMedCrossRef
14.
go back to reference Meng L, Rong FW, Chun LZ et al (2007) Noninvasive imaging of human telomerase reverse transcriptase (hTERT) messenger RNA with 99mTC-radiolabeled antisense probes in malignant tumors. J Nucl Med 48:2028–2036CrossRef Meng L, Rong FW, Chun LZ et al (2007) Noninvasive imaging of human telomerase reverse transcriptase (hTERT) messenger RNA with 99mTC-radiolabeled antisense probes in malignant tumors. J Nucl Med 48:2028–2036CrossRef
15.
go back to reference Novakovic S, Hocevar M, Zgajnar J et al (2004) Detection of telomerase RNA in the plasma of patients with breast cancer, malignant melanoma or thyroid cancer. Oncol Rep 11:245–252PubMed Novakovic S, Hocevar M, Zgajnar J et al (2004) Detection of telomerase RNA in the plasma of patients with breast cancer, malignant melanoma or thyroid cancer. Oncol Rep 11:245–252PubMed
16.
go back to reference Liliana T, Enrica R, Salvatore P et al (2008) Relationship between tumor and plasma levels of hTERT mRNA in patients with colorectal cancer: implications for monitoring of neoplastic disease. Clin Cancer Res 14:7444–7451CrossRef Liliana T, Enrica R, Salvatore P et al (2008) Relationship between tumor and plasma levels of hTERT mRNA in patients with colorectal cancer: implications for monitoring of neoplastic disease. Clin Cancer Res 14:7444–7451CrossRef
17.
go back to reference Masutomi K, Shuichi K, Mami Y et al (2002) Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma. Oncogene 21:5946–5950PubMedCrossRef Masutomi K, Shuichi K, Mami Y et al (2002) Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma. Oncogene 21:5946–5950PubMedCrossRef
18.
go back to reference Miura N, Maruyama S, Oyama K et al (2007) Development of a novel assay to quantify serum human telomerase reverse transcriptase messenger RNA and its significance as a tumor marker for hepatocellular carcinoma. Oncology 72:45–51PubMedCrossRef Miura N, Maruyama S, Oyama K et al (2007) Development of a novel assay to quantify serum human telomerase reverse transcriptase messenger RNA and its significance as a tumor marker for hepatocellular carcinoma. Oncology 72:45–51PubMedCrossRef
19.
go back to reference Mezzasoma L, Antognelli C, Del Buono C et al (2010) Expression and biological-clinical significance of hTR, hTERT and CKS2 in washing fluids of patients with bladder cancer. BMC Urol 10:1–10CrossRef Mezzasoma L, Antognelli C, Del Buono C et al (2010) Expression and biological-clinical significance of hTR, hTERT and CKS2 in washing fluids of patients with bladder cancer. BMC Urol 10:1–10CrossRef
21.
go back to reference Gabriele S (2009) Telomerase, mitochondria and oxidative stress. Exp Gerontol 44:485–492CrossRef Gabriele S (2009) Telomerase, mitochondria and oxidative stress. Exp Gerontol 44:485–492CrossRef
22.
go back to reference Hiyama E, Hiyama K, Tatsumoto N et al (1996) Telomerase activity in human intestine. Int J Oncol 9:453–458PubMed Hiyama E, Hiyama K, Tatsumoto N et al (1996) Telomerase activity in human intestine. Int J Oncol 9:453–458PubMed
23.
go back to reference Ali ASM, Chopra R, Robertson J et al (2000) Detection of hTERT protein by flow cytometry. Leukemia 14:2176–2181PubMedCrossRef Ali ASM, Chopra R, Robertson J et al (2000) Detection of hTERT protein by flow cytometry. Leukemia 14:2176–2181PubMedCrossRef
24.
go back to reference XU D, Gruber A, Peterson C et al (1998) Telomerase activity and the expression of telomerase components in acute myelogenous leukaemia. Br J Haematol 102:1367–1375PubMedCrossRef XU D, Gruber A, Peterson C et al (1998) Telomerase activity and the expression of telomerase components in acute myelogenous leukaemia. Br J Haematol 102:1367–1375PubMedCrossRef
25.
go back to reference Jong HS, Park YI, Kim S et al (1999) Up-regulation of human telomerase catalytic subunit during gastric carcinogenesis. Cancer 15:559–565CrossRef Jong HS, Park YI, Kim S et al (1999) Up-regulation of human telomerase catalytic subunit during gastric carcinogenesis. Cancer 15:559–565CrossRef
26.
go back to reference Toshikuni N, Nouso K, Higashi T et al (2000) Expression of telomerase-associated protein 1 and telomerase reverse transcriptase in hepatocellular carcinoma. Br J Cancer 82:833–837PubMedCrossRef Toshikuni N, Nouso K, Higashi T et al (2000) Expression of telomerase-associated protein 1 and telomerase reverse transcriptase in hepatocellular carcinoma. Br J Cancer 82:833–837PubMedCrossRef
27.
go back to reference Kirkpatrick KL, Clark G, Ghilchick M et al (2003) hTERT mRNA expression correlates with telomerase activity in human breast cancer. Eur J Surg Oncol 29:321–326PubMedCrossRef Kirkpatrick KL, Clark G, Ghilchick M et al (2003) hTERT mRNA expression correlates with telomerase activity in human breast cancer. Eur J Surg Oncol 29:321–326PubMedCrossRef
28.
go back to reference Ramirez JL, Sarries C, de Castro PL et al (2003) Methylation patterns and K-ras mutations in tumor and paired serum of resected non-small-cell lung cancer patients. Cancer Lett 193:207–216PubMedCrossRef Ramirez JL, Sarries C, de Castro PL et al (2003) Methylation patterns and K-ras mutations in tumor and paired serum of resected non-small-cell lung cancer patients. Cancer Lett 193:207–216PubMedCrossRef
29.
go back to reference Kim NW, Piatyszek MA, Prowse KR et al (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 226:2011–2015CrossRef Kim NW, Piatyszek MA, Prowse KR et al (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 226:2011–2015CrossRef
30.
go back to reference Poole JC, Andrews LG, Tollefsbol TO (2001) Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene 269:1–12PubMedCrossRef Poole JC, Andrews LG, Tollefsbol TO (2001) Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene 269:1–12PubMedCrossRef
31.
go back to reference Orlando C, Gelmini S, Selli C et al (2001) Telomerase in urological malignancy. J Urol 166:666–673PubMedCrossRef Orlando C, Gelmini S, Selli C et al (2001) Telomerase in urological malignancy. J Urol 166:666–673PubMedCrossRef
32.
go back to reference Zhang Y, He DM (2002) Effect of antisense hTERT mRNA oligodeoxynucleotide on telomerase activity of leukemic cells. Cell Biol Int 26:427–431PubMedCrossRef Zhang Y, He DM (2002) Effect of antisense hTERT mRNA oligodeoxynucleotide on telomerase activity of leukemic cells. Cell Biol Int 26:427–431PubMedCrossRef
33.
go back to reference Peter JFS, Roderick HJB, Thomas GS et al (2004) Elevated hTERT mRNA levels: a potential determinant of bronchial squamous cell carcinoma (in situ). Int J Cancer 109:412–417CrossRef Peter JFS, Roderick HJB, Thomas GS et al (2004) Elevated hTERT mRNA levels: a potential determinant of bronchial squamous cell carcinoma (in situ). Int J Cancer 109:412–417CrossRef
34.
go back to reference Francisco D, Salvador L, Eduardo GG et al (2001) Real-time quantification in plasma of human telomerase reverse transcriptase (hTERT) mRNA: a simple blood test to monitor disease in cancer patients. Lab Invest 81:767–769CrossRef Francisco D, Salvador L, Eduardo GG et al (2001) Real-time quantification in plasma of human telomerase reverse transcriptase (hTERT) mRNA: a simple blood test to monitor disease in cancer patients. Lab Invest 81:767–769CrossRef
35.
go back to reference Kirkpatrick KL, Ogunkolade W, Elkak AE et al (2003) hTERT expression in human breast cancer and non-cancerous breast tissue: correlation with tumour stage and c-Myc expression. Breast Cancer Res Treat 77:277–284PubMedCrossRef Kirkpatrick KL, Ogunkolade W, Elkak AE et al (2003) hTERT expression in human breast cancer and non-cancerous breast tissue: correlation with tumour stage and c-Myc expression. Breast Cancer Res Treat 77:277–284PubMedCrossRef
36.
go back to reference Salhab M, Jiang WG, Newbold RF et al (2008) The expression of gene transcripts of telomere-associated genes in human breast cancer: correlation with clinico-pathological parameters and clinical outcome. Breast Cancer Res Treat 109:35–46PubMedCrossRef Salhab M, Jiang WG, Newbold RF et al (2008) The expression of gene transcripts of telomere-associated genes in human breast cancer: correlation with clinico-pathological parameters and clinical outcome. Breast Cancer Res Treat 109:35–46PubMedCrossRef
37.
go back to reference Li YR, Wu JM, Wang L et al (2005) Human telomerase reverse transcriptase expression and its clinical significance in laryngeal squamous cell carcinoma. Acta Otolaryngol 125:409–414PubMedCrossRef Li YR, Wu JM, Wang L et al (2005) Human telomerase reverse transcriptase expression and its clinical significance in laryngeal squamous cell carcinoma. Acta Otolaryngol 125:409–414PubMedCrossRef
38.
go back to reference Miura N, Kanamori Y, Takahashi M et al (2007) A diagnostic evaluation of serum human telomerase reverse transcriptase mRNA as a novel tumor marker for gynecologic malignancies. Oncol Rep 17:541–548PubMed Miura N, Kanamori Y, Takahashi M et al (2007) A diagnostic evaluation of serum human telomerase reverse transcriptase mRNA as a novel tumor marker for gynecologic malignancies. Oncol Rep 17:541–548PubMed
39.
go back to reference Miura N, Maeda Y, Kanbe T et al (2005) Serum human telomerase reverse transcriptase messenger RNA as a novel tumor marker for hepatocellular carcinoma. Clin Cancer Res 11:3205–3209PubMedCrossRef Miura N, Maeda Y, Kanbe T et al (2005) Serum human telomerase reverse transcriptase messenger RNA as a novel tumor marker for hepatocellular carcinoma. Clin Cancer Res 11:3205–3209PubMedCrossRef
40.
go back to reference Miura N, Osaki Y, Nagashima M et al (2010) A novel biomarker TERT mRNA is applicable for early detection of hepatoma. BMC Gastroenterol 10:1–12CrossRef Miura N, Osaki Y, Nagashima M et al (2010) A novel biomarker TERT mRNA is applicable for early detection of hepatoma. BMC Gastroenterol 10:1–12CrossRef
41.
go back to reference Mahendar P, Radhika T, Anwar M et al (2011) Evaluation of serum human telomerase reverse transcriptase as a novel marker for cervical cancer. Int J Biol Markers 26:22–26. doi:10.5301/JBM.2011.6352 Mahendar P, Radhika T, Anwar M et al (2011) Evaluation of serum human telomerase reverse transcriptase as a novel marker for cervical cancer. Int J Biol Markers 26:22–26. doi:10.​5301/​JBM.​2011.​6352
42.
go back to reference 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
43.
go back to reference He DM, Zhang H (2004) Telomerase activity and hTERT mRNA expression in acute leukemia. Chin J Cancer Res 16:289–291CrossRef He DM, Zhang H (2004) Telomerase activity and hTERT mRNA expression in acute leukemia. Chin J Cancer Res 16:289–291CrossRef
44.
go back to reference Chun L, Ming-Yao W, Ying-Rui L et al (2003) Correlation between expression of human telomerase subunits and telomerase activity in esophageal squamous cell carcinoma. World J Gastroenterol 9:2395–2399 Chun L, Ming-Yao W, Ying-Rui L et al (2003) Correlation between expression of human telomerase subunits and telomerase activity in esophageal squamous cell carcinoma. World J Gastroenterol 9:2395–2399
Metadata
Title
Serum human telomerase reverse transcriptase: a novel biomarker for breast cancer diagnosis
Authors
Mahendar Porika
Radhika Tippani
Sekhar R. Bollam
Sree Divya Panuganti
Christopher Thamidala
Sadanandam Abbagani
Publication date
01-12-2011
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 6/2011
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-011-0230-6

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