Relationship between tumor and plasma levels of hTERT mRNA in patients with colorectal cancer: Implications for monitoring of neoplastic disease
Open accessAbstract
Purpose: Colorectal cancer (CRC) is one of the most common cancers in western countries. Identification of circulating markers for CRC would optimize early stage diagnosis and the monitoring for disease recurrence. Expression of telomerase reverse transcriptase (hTERT) is essential to the oncogenic process and might be used as a molecular marker of neoplastic disease. Experimental Design: Eighty-five CRC samples (25 stage I, 15 stage II, 15 stage III, and 30 stage IV), the available corresponding noncancerous mucosa (n = 42), and plasma collected at the time of surgery (n = 49) were analyzed. Control plasma samples were obtained from 43 age-matched healthy subjects. All hTERT transcripts (hTERT-AT) and transcripts encoding the functional protein (hTERT-FL) were quantified by real-time PCR. Results: hTERT-AT was found to correlate with hTERT-FL (r = 0.849; P < 0.0001) mRNA levels in tumors. Both hTERT mRNAs were significantly higher in tumors than in adjacent noncancerous mucosa and both significantly increased with tumor progression (P < 0.0001). In contrast to controls, all but two plasma samples from CRC patients were positive for hTERT mRNAs. Using the cutoff value of 180 copies hTERT-AT/mL, the sensitivity and specificity of the assay for CRC detection were 92% and 100%, respectively. Furthermore, hTERT-AT mRNA levels in plasma significantly correlated with hTERT-AT mRNA levels in tumors (r = 0.702, P < 0.0001). Conclusions: These findings indicate that quantification of hTERT mRNA in plasma may be used as a marker for detection and monitoring of neoplastic colorectal disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The identification of hTERT transcripts in the plasma of CRC patients may serve as a useful tool for disease monitoring, as mRNA levels correlate with those found in tumors.
“In fact, the identification of hTERT transcripts in the plasma of CRC patients may serve as a useful tool for disease monitoring, as mRNA levels correlate with those found in tumors [208].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [208]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Gentleman R: R: A language for data analysis and graphics
Ihaka, R., & Gentleman, R. (1996) · Journal of Computational and Graphical Statistics · doi:10.1080/10618600.1996.10474713 · Cited by 11,747 · see citing works
(2002) · Springer eBooks · doi:10.1007/978-1-4757-3656-4 · Cited by 6,375 · see citing works
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256 · see citing works
Stability of Endogenous and Added RNA in Blood Specimens, Serum, and Plasma
Tsui, N. B. Y., Ng, E. K. O., & Lo, Y. D. (2002) · Clinical Chemistry · doi:10.1093/clinchem/48.10.1647 · Cited by 628 · see citing works
de Kok, J. B., Roelofs, R., Giesendorf, B. A. J., Pennings, J. L. A., Waas, E. T., Feuth, T. B., Swinkels, D. W., & Span, P. N. (2004) · Laboratory Investigation · doi:10.1038/labinvest.3700208 · Cited by 580 · see citing works
Ulaner, G. A., Hu, J., Vu, T. H., Giudice, L. C., & Hoffman, A. R. (1998) · PubMed · Cited by 495 · see citing works
Expression of TERT in early premalignant lesions and a subset of cells in normal tissues
Kolquist, K. A., Ellisen, L. W., Counter, C. M., Meyerson, M. M., Tan, L. K., Weinberg, R. A., Haber, D. A., & Gerald, W. L. (1998) · Nature Genetics · doi:10.1038/554 · Cited by 382 · see citing works
Sozzi, G., Conte, D., Mariani, L., Vullo, S. L., Roz, L., Lombardo, C., Pierotti, M. A., & Tavecchio, L. (2001) · PubMed · Cited by 380 · see citing works
Kim, G. P., Colangelo, L. H., Wieand, H. S., Paik, S., Kirsch, I. R., Wolmark, N., & Allegra, C. J. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.05.8172 · Cited by 340 · see citing works
El‐Hefnawy, T., Raja, S., Kelly, L. A., Bigbee, W. L., Kirkwood, J. M., Luketich, J. D., & Godfrey, T. E. (2004) · Clinical Chemistry · doi:10.1373/clinchem.2003.028506 · Cited by 273 · see citing works
Telomerase RNA as a detection marker in the serum of breast cancer patients.
Chen, X. Q., Bonnefoi, H. R., Pelte, M. F., Lyautey, J., Lederrey, C., Movarekhi, S., Schaeffer, P., Mulcahy, H. E., Meyer, P., Stroun, M., et al. (2000) · PubMed · Cited by 242 · see citing works
Gertler, R., Rosenberg, R., Stricker, D., Friederichs, J., Hoos, A., Werner, M., Ulm, K., Holzmann, B., Nekarda, H., & Siewert, J.-R. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.09.160 · Cited by 180 · see citing works
Targeting the Limitless Replicative Potential of Cancer: The Telomerase/Telomere Pathway
Kèlland, L. R. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0422 · Cited by 142 · see citing works
Tatsumoto, N., Hiyama, E., Murakami, Y., Imamura, Y., Shay, J. W., Matsuura, Y., & Yokoyama, T. (2000) · PubMed · Cited by 132 · see citing works
Genetic and epigenetic modulation of telomerase activity in development and disease
Liu, L., Lai, S. R., Andrews, L. G., & Tollefsbol, T. O. (2004) · Gene · doi:10.1016/j.gene.2004.06.011 · Cited by 121 · see citing works
Menin, C., Scaini, M. C., Salvo, G. L. D., Biscuola, M., Quaggio, M., Esposito, G., Belluco, C., Montagna, M., Agata, S., D’Andrea, E., et al. (2006) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djj054 · Cited by 121 · see citing works
Self-citationGarcia‐Aranda, C., de Juan, C., Diaz‐Lopez, A., Sanchez‐Pernaute, A., Torres, A., Diaz‐Rubio, E., Balibrea, J., Benito, M., & Iniesta, P. (2006) · Cancer · doi:10.1002/cncr.21625 · Cited by 105 · see citing works
Wang, J., Lin, S., Wu, D., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2054 · Cited by 83 · see citing works
Hsieh, J., Lin, S., Chang, M., et al. (2005) · The American Surgeon · doi:10.1177/000313480507100413 · Cited by 81 · see citing works
Miura, N., Maeda, Y., Kanbe, T., Yazama, H., Takeda, Y., Sato, R., Tsukamoto, T., Sato, E., Marumoto, A., Harada, T., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1487 · Cited by 77 · see citing works
Terrin, L., Trentin, L., Degan, M., Corradini, I., Bertorelle, R., Carli, P., Maschio, N., Bo, M. D., Noventa, F., Gattei, V., et al. (2007) · Leukemia · doi:10.1038/sj.leu.2404607 · Cited by 64 · see citing works
Self-citationEsposito, G., Pucciarelli, S., Alaggio, R., Giacomelli, L., Marchiori, E., Iaderosa, G. A., Friso, M. L., Toppan, P., Chieco‐Bianchi, L., & Lise, M. (2001) · Annals of Surgical Oncology · doi:10.1007/s10434-001-0311-2 · Cited by 64 · see citing works
Self-citationDômont, J., Pawlik, T. M., Boige, V., Rosé, M., Weber, J. C., Hoff, P. M., Brown, T. D., Zorzi, D., Morat, L., Pignon, J., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.06.944 · Cited by 61 · see citing works
Lledó, S., García‐Granero, E., Dası́, F., Ripoli, R., García, S. A., Cervantes, A. M. R., & Aliño, S. F. (2004) · Colorectal Disease · doi:10.1111/j.1463-1318.2004.00627.x · Cited by 60 · see citing works
Telomerase Detection in Body Fluids
Hess, J. L., & Highsmith, W. E. (2002) · Clinical Chemistry · doi:10.1093/clinchem/48.1.18 · Cited by 50 · see citing works
Tani, N., Ichikawa, D., Ikoma, D., et al. (2007) · PubMed · Cited by 50 · see citing works
Human Immunodeficiency Virus Type 1 Modulates Telomerase Activity in Peripheral Blood Lymphocytes
Ballon, G., Ometto, L., Righetti, E., Cattelan, A. M., Masiero, S., Zanchetta, M., Chieco‐Bianchi, L., & Rossi, A. D. (2001) · The Journal of Infectious Diseases · doi:10.1086/318072 · Cited by 49 · see citing works
Epithelial Molecular Markers in the Peripheral Blood of Patients with Colorectal Cancer
Khair, G., Monson, J. R. T., & Greenman, J. (2007) · Diseases of the Colon & Rectum · doi:10.1007/s10350-006-0875-9 · Cited by 46 · see citing works
Dası́, F., Martínez-Rodés, P., MARCH, J. A., et al. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1368.028 · Cited by 45 · see citing works
Gertler, R., Rosenberg, R., Stricker, D., Werner, M., Laßmann, S., Ulm, K., Nekarda, H., & Siewert, J. R. (2002) · Cancer · doi:10.1002/cncr.10939 · Cited by 43 · see citing works
Quantitative analysis of hTERT mRNA expression in colorectal cancer
Niiyama, H., Mizumoto, K., Sato, N., Nagai, E., Mibu, R., Fukui, T., Kinoshita, M., & Tanaka, M. (2001) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.03890.x · Cited by 42 · see citing works
Nowak, J., Januszkiewicz, D., Lewandowski, K., Nowicka-Kujawska, K., Pernak, M., Rembowska, J., Nowak, T., & Wysocki, J. (2003) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200301000-00013 · Cited by 38 · see citing works
Terrin, L., Dolcetti, R., Corradini, I., Indraccolo, S., Col, J. D., Bertorelle, R., Bonaldi, L., Esposito, G., & Rossi, A. D. (2007) · International Journal of Cancer · doi:10.1002/ijc.22661 · Cited by 37 · see citing works
Self-citationZaffaroni, N., Villa, R., Pastorino, U., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1293 · Cited by 36 · see citing works
Genomic Profiling of Circulating Plasma RNA for the Analysis of Cancer
Collado, M., García‐Barberán, V., Garcia, J. M., Alonso, I., Lombardía, L., Díaz‐Uriarte, R., López-Fernández, L. A., Zaballos, Á., Bonilla, F., & Serrano, M. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2007.089201 · Cited by 33 · see citing works
Specht, C., Bexten, S., Kölsch, E., & Pauels, H. (2001) · International Journal of Cancer · doi:10.1002/1097-0215(200002)9999:9999 · Cited by 31 · see citing works
Optimization of an RNA isolation procedure from plasma samples
Cerkovnik, P., Perhavec, A., Žgajnar, J., et al. (2007) · International Journal of Molecular Medicine · doi:10.3892/ijmm.20.3.293 · Cited by 29 · see citing works
Naito, Y., Takagi, T., Handa, O., Ishikawa, T., Matsumoto, N., Yoshida, N., Kato, H., Ando, T., Takemura, T., Itani, K., et al. (2001) · Tumor Biology · doi:10.1159/000050640 · Cited by 25 · see citing works
Harnessing Telomerase in Cancer Therapeutics
Fakhoury, J. J., Nimmo, G. A. M., & Autexier, C. (2007) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/187152007781058622 · Cited by 24 · see citing works
Telomerase as a diagnostic and predictive marker in colorectal carcinoma.
Maláska, J., Kunická, Z., Borský, M., Skleničková, M., Novotna, M., Fajkusová, L., Žaloudík, J., & Fajkus, J. (2004) · PubMed · Cited by 23 · see citing works
Pelosi, G., Schianchi, E., Dell’Orto, P., et al. (2005) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-005-0087-z · Cited by 20 · see citing works
Ghori, A., Usselmann, B., Ferryman, S. R., Morris, A. G., & Fraser, I. A. (2002) · Colorectal Disease · doi:10.1046/j.1463-1318.2002.00378.x · Cited by 17 · see citing works
Murillo-Ortiz, B. O., la Vega, H. A., Castillo-Medina, S., Malacara, J. M., & Benı́tez-Bribiesca, L. (2006) · BMC Cancer · doi:10.1186/1471-2407-6-206 · Cited by 17 · see citing works
Regulation of telomerase and its hTERT messenger in colorectal cancer
Boldrini, L., Faviana, P., Gisfredi, S., et al. (2004) · Oncology Reports · doi:10.3892/or.11.2.395 · Cited by 17 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Esposito G, Pucciarelli S, Alaggio R, et al. 27kip1 ex- pression is associated with tumor response to preop- erative chemoradiotherapy in rectal cancer. Ann Surg Oncol 2001;8:311 ^8.
- Garcia-Aranda C, de Juan C, Diaz-Lopez A, et al. Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1expression in co- lorectal carcinoma. Cancer 2006;106:541 ^51.
- Ulaner GA, Hu JF, VuTH, Giudice LC, Hoffman AR. Tissue-specific alternate splicing of human telomerase reverse transcriptase (hTERT) influences telomere lengths during human development. Int J Cancer 2001;91:644 ^9.
- Greene FL, Page DL, Fleming ID, et al, eds. Ameri- can Joint Committee on Cancer Staging Manual. 6th ed. Philadelphia: Springer; 2002.
- Ballon G, Ometto L, Righetti E, et al. Human immu- nodeficiency virus type 1modulates telomerase activ- ity in peripheral blood lymphocytes. J Infect Dis 2001; 183:417 ^24.
Cited by
Sorted by citations
Liu, Z., Li, Q., Li, K., Chen, L., Li, W., Hou, M., Liu, T., Yang, J., Lindvall, C., Björkholm, M., et al. (2013) · Oncogene · doi:10.1038/onc.2012.441 · Cited by 276 · see citing works
Rampazzo, E., Bertorelle, R., Serra, L., Terrin, L., Candiotto, C., Pucciarelli, S., Bianco, P. D., Nitti, D., & De Rossi, A. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6605644 · Cited by 125 · see citing works
Self-citationTelomeres, telomerase and colorectal cancer
Bertorelle, R. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i8.1940 · Cited by 82 · see citing works
Self-citationBertorelle, R., Briarava, M., Rampazzo, E., Biasini, L., Agostini, M., Maretto, I., Lonardi, S., Friso, M. L., Mescoli, C., Zagonel, V, et al. (2013) · British Journal of Cancer · doi:10.1038/bjc.2012.602 · Cited by 77 · see citing works
Self-citationCurrent and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy
Nikolouzakis, T. K., Chrysos, E., Docea, A. O., Fragkiadaki, P., Souglakos, J., Tsiaoussis, J., & Tsatsakis, A. (2024) · Cancers · doi:10.3390/cancers16111995 · Cited by 37 · see citing works
Telomeres and telomerase in the clinical management of colorectal cancer
Piñol-Felis, C., Fernández-Marcelo, T., Viñas-Salas, J., & Valls-Bautista, C. (2017) · Clinical and Translational Oncology · doi:10.1007/s12094-016-1559-0 · Cited by 13 · see citing works
Laish, I., Levi, Z., Mahajna, H., Albshesh, A., Horesh, N., Katz, E., Feldman, D., Shinar, N., Picard, O., Yavzori, M., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.962473 · Cited by 6 · see citing works
- Authors
- Terrin, L., Rampazzo, E., Pucciarelli, S., Agostini, M., Bertorelle, R., Esposito, G., DelBianco, P., Nitti, D., & De Rossi, A.
- Affiliations
- Istituto Oncologico Veneto (IT)
- University of Padua (IT)
- 3Istituto Oncologico Veneto-IRCCS, Padova, Italy
- 1Department of Oncology and Surgical Sciences, Section of Oncology,
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2008-11-14
- Volume
- 14
- Issue
- 22
- Pages
- 7444-7451
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2139801283
- Cited by
- 91
- References
- 44
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 8 · 2017: 7 · 2016: 7 · 2015: 9 · 2014: 13 · 2013: 7 · 2012: 4
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- colorectal cancer, hTERT mRNA, telomerase reverse transcriptase, circulating tumor markers, plasma biomarkers, tumor progression, tumor recurrence monitoring, early cancer detection
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Immunohistochemistry, Male, Middle Aged, Prognosis, RNA, Messenger, ROC Curve, Sensitivity and Specificity, Colorectal Neoplasms, Biomarkers, Disease Progression, Telomerase, Reverse Transcriptase Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
