dc.contributor.author |
Sanmartín, Elena
|
es_ES |
dc.contributor.author |
Sirera Pérez, Rafael
|
es_ES |
dc.contributor.author |
Usó, Marta
|
es_ES |
dc.contributor.author |
Blasco, Ana
|
es_ES |
dc.contributor.author |
Gallach, Sandra
|
es_ES |
dc.contributor.author |
Figueroa, Santiago
|
es_ES |
dc.contributor.author |
Martínez, Nieves
|
es_ES |
dc.contributor.author |
Hernando, Cristina
|
es_ES |
dc.contributor.author |
Honguero, Antonio
|
es_ES |
dc.contributor.author |
Martorell, Miguel
|
es_ES |
dc.contributor.author |
Guijarro, Ricardo
|
es_ES |
dc.contributor.author |
Rosell, Rafael
|
es_ES |
dc.contributor.author |
Jantus-Lewintre, Eloisa
|
es_ES |
dc.contributor.author |
Camps, Carlos
|
es_ES |
dc.date.accessioned |
2017-05-11T12:29:23Z |
|
dc.date.available |
2017-05-11T12:29:23Z |
|
dc.date.issued |
2014-02 |
|
dc.identifier.issn |
1068-9265 |
|
dc.identifier.uri |
http://hdl.handle.net/10251/80997 |
|
dc.description.abstract |
[EN] Background. Angiogenesis and lymphangiogenesis are key mechanisms for tumor growth and dissemination. They are mainly regulated by the vascular endothelial growth factor (VEGF) family of ligands and receptors. The aim of this study was to analyze relative expression levels of angiogenic markers in resectable non-small cell lung cancer patients in order to asses a prognostic signature that could improve characterization of patients with worse clinical outcomes.
Methods. RNA was obtained from tumor and normal lung specimens from 175 patients. Quantitative polymerase chain reaction was performed to analyze the relative expression of HIF1A, PlGF, VEGFA, VEGFA(165b), VEGFB, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, NRP1 and NRP2.
Results. Univariate analysis showed that tumor size and ECOG-PS are prognostic factors for time to progression (TTP) and overall survival (OS). This analysis in the case of angiogenic factors also revealed that PlGF, VEGFA, VEGFB and VEGFD distinguish patients with different outcomes. Taking into account the complex interplay between the different ligands of the VEGF family and to more precisely predict the outcome of the patients, we considered a new analysis combining several VEGF ligands. In order to find independent prognostic variables, we performed a multivariate Cox analysis, which showed that the subgroup of patients with higher relative expression of VEGFA plus lower VEGFB and VEGFD presented the poorest outcome for both TTP and OS.
Conclusions. The relative expression of these three genes can be considered as an angiogenic gene signature whose applicability for the selection of candidates for targeted therapies needs to be further validated. |
es_ES |
dc.description.sponsorship |
This study was partially supported by a grant from the Instituto de Salud Carlos III (FIS PI06/1041 and PS09/1149), Red Tematica de Investigacion Cooperativa en Cancer (RD06/0020/1024), and FEDER. |
en_EN |
dc.language |
Inglés |
es_ES |
dc.publisher |
Springer Verlag (Germany) |
es_ES |
dc.relation.ispartof |
Annals of Surgical Oncology |
es_ES |
dc.rights |
Reserva de todos los derechos |
es_ES |
dc.subject |
Endothelial-growth-factor |
es_ES |
dc.subject |
Inhibitory splice variant |
es_ES |
dc.subject |
Lymph-node metastasis |
es_ES |
dc.subject |
VEGF-C |
es_ES |
dc.subject |
Breast cancer |
es_ES |
dc.subject |
Colorectal cancer |
es_ES |
dc.subject |
Carcinoma |
es_ES |
dc.subject |
Tumor |
es_ES |
dc.subject |
Receptors |
es_ES |
dc.subject |
Lymphangiogenesis |
es_ES |
dc.subject.classification |
MICROBIOLOGIA |
es_ES |
dc.title |
A Gene Signature Combining the Tissue Expression of Three Angiogenic Factors is a Prognostic Marker in Early-stage Non-small Cell Lung Cancer |
es_ES |
dc.type |
Artículo |
es_ES |
dc.identifier.doi |
10.1245/s10434-013-3330-x |
|
dc.relation.projectID |
info:eu-repo/grantAgreement/ISCIII//PI06%2F1041/ |
|
dc.relation.projectID |
info:eu-repo/grantAgreement/ISCIII//PS09%2F1149/ |
|
dc.relation.projectID |
info:eu-repo/grantAgreement/MSC//RD06%2F0020%2F1024/ES/RED TEMÁTICA DE INVESTIGACIÓN COOPERATIVA DEL CANCER/ |
|
dc.rights.accessRights |
Cerrado |
es_ES |
dc.contributor.affiliation |
Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural - Escola Tècnica Superior d'Enginyeria Agronòmica i del Medi Natural |
es_ES |
dc.description.bibliographicCitation |
Sanmartín, E.; Sirera Pérez, R.; Usó, M.; Blasco, A.; Gallach, S.; Figueroa, S.; Martínez, N.... (2014). A Gene Signature Combining the Tissue Expression of Three Angiogenic Factors is a Prognostic Marker in Early-stage Non-small Cell Lung Cancer. Annals of Surgical Oncology. 21(2):612-620. https://doi.org/10.1245/s10434-013-3330-x |
es_ES |
dc.description.accrualMethod |
S |
es_ES |
dc.relation.publisherversion |
http://doi.org/10.1245/s10434-013-3330-x |
es_ES |
dc.description.upvformatpinicio |
612 |
es_ES |
dc.description.upvformatpfin |
620 |
es_ES |
dc.type.version |
info:eu-repo/semantics/publishedVersion |
es_ES |
dc.description.volume |
21 |
es_ES |
dc.description.issue |
2 |
es_ES |
dc.relation.senia |
282057 |
es_ES |
dc.identifier.eissn |
1534-4681 |
|
dc.identifier.pmid |
24145997 |
|
dc.contributor.funder |
Instituto de Salud Carlos III |
|
dc.contributor.funder |
Red Temática de Investigación Cooperativa en Cáncer |
|
dc.contributor.funder |
European Regional Development Fund |
|
dc.contributor.funder |
Ministerio de Sanidad y Consumo |
es_ES |
dc.description.references |
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. |
es_ES |
dc.description.references |
Spiro SG, Tanner NT, Silvestri GA, et al. Lung cancer: progress in diagnosis, staging and therapy. Respirology. 2010;15:44–50. |
es_ES |
dc.description.references |
Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008;3:819–31. |
es_ES |
dc.description.references |
Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–27. |
es_ES |
dc.description.references |
Veikkola T, Karkkainen M, Claesson-Welsh L, Alitalo K. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res. 2000;60:203–12. |
es_ES |
dc.description.references |
Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008;358:2039–49. |
es_ES |
dc.description.references |
Dvorak HF. Angiogenesis: update, 2005. J Thromb Haemost. 2005;3:1835–42. |
es_ES |
dc.description.references |
Mattern J, Koomagi R, Volm M. Coexpression of VEGF and bFGF in human epidermoid lung carcinoma is associated with increased vessel density. Anticancer Res. 1997;17:2249–52. |
es_ES |
dc.description.references |
Bremnes RM, Camps C, Sirera R. Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer. 2006;51:143–58. |
es_ES |
dc.description.references |
Zhu CQ, Shih W, Ling CH, Tsao MS. Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol. 2006;59:790–800. |
es_ES |
dc.description.references |
Zhan P, Wang J, Lv XJ, et al. Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: a systematic review with meta-analysis. J Thorac Oncol. 2009;4:1094–103. |
es_ES |
dc.description.references |
Salgia R. Prognostic significance of angiogenesis and angiogenic growth factors in nonsmall cell lung cancer. Cancer. 2011;117:3889–99. |
es_ES |
dc.description.references |
Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001;7:192–8. |
es_ES |
dc.description.references |
Pepper MS, Tille JC, Nisato R, Skobe M. Lymphangiogenesis and tumor metastasis. Cell Tissue Res. 2003;314:167–77. |
es_ES |
dc.description.references |
Yokoyama Y, Charnock-Jones DS, Licence D, et al. Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma. Br J Cancer. 2003;88:237–44. |
es_ES |
dc.description.references |
Ko YH, Jung CK, Lee MA, et al. Clinical significance of vascular endothelial growth factors (VEGF)-C and -D in resected non-small cell lung cancer. Cancer Res Treat. 2008;40:133–40. |
es_ES |
dc.description.references |
Maekawa S, Iwasaki A, Shirakusa T, et al. Correlation between lymph node metastasis and the expression of VEGF-C, VEGF-D and VEGFR-3 in T1 lung adenocarcinoma. Anticancer Res. 2007;27:3735–41. |
es_ES |
dc.description.references |
Niki T, Iba S, Tokunou M, Yamada T, Matsuno Y, Hirohashi S. Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma. Clin Cancer Res. 2000;6:2431–9. |
es_ES |
dc.description.references |
Feng Y, Wang W, Hu J, Ma J, Zhang Y, Zhang J. Expression of VEGF-C and VEGF-D as significant markers for assessment of lymphangiogenesis and lymph node metastasis in non-small cell lung cancer. Anat Rec (Hoboken). 2010;293:802–12. |
es_ES |
dc.description.references |
Greene FL, Page DL, Fleming ID, et al. AJCC cancer staging manual. New York: Springer; 2002. |
es_ES |
dc.description.references |
Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45. |
es_ES |
dc.description.references |
Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76. |
es_ES |
dc.description.references |
Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542–50. |
es_ES |
dc.description.references |
Donnem T, Al Saad S, Al Shibli K, et al. Inverse prognostic impact of angiogenic marker expression in tumor cells versus stromal cells in non small cell lung cancer. Clin Cancer Res. 2007;13:6649–57. |
es_ES |
dc.description.references |
Pajares MJ, Agorreta J, Larrayoz M, et al. Expression of tumor-derived vascular endothelial growth factor and its receptors is associated with outcome in early squamous cell carcinoma of the lung. J Clin Oncol. 2012;30:1129–36. |
es_ES |
dc.description.references |
Carrillo de Santa PE, Arias FC, Caso PE, et al. Prognostic significance of the expression of vascular endothelial growth factors A, B, C, and D and their receptors R1, R2, and R3 in patients with nonsmall cell lung cancer. Cancer. 2009;115:1701–12. |
es_ES |
dc.description.references |
Bonnesen B, Pappot H, Holmstav J, Skov BG. Vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 expression in non-small cell lung cancer patients: relation to prognosis. Lung Cancer. 2009;66:314–8. |
es_ES |
dc.description.references |
Seto T, Higashiyama M, Funai H, et al. Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small-cell lung cancer. Lung Cancer. 2006;53:91–6. |
es_ES |
dc.description.references |
Reinmuth N, Thomas M, Meister M, Schnabel PA, Kreuter M. Current data on predictive markers for anti-angiogenic therapy in thoracic tumours. Eur Respir J. 2010;36:915–24. |
es_ES |
dc.description.references |
Jantus-Lewintre E, Sanmartin E, Sirera R, et al. Combined VEGF-A and VEGFR-2 concentrations in plasma: diagnostic and prognostic implications in patients with advanced NSCLC. Lung Cancer. 2011;74:326–31. |
es_ES |
dc.description.references |
Dowlati A, Gray R, Sandler AB, Schiller JH, Johnson DH. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab—an Eastern Cooperative Oncology Group Study. Clin Cancer Res. 2008;14:1407–12. |
es_ES |
dc.description.references |
Hanrahan EO, Ryan AJ, Mann H, et al. Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. Clin Cancer Res. 2009;15:3600–9. |
es_ES |
dc.description.references |
Bates DO, Cui TG, Doughty JM, et al. VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. Cancer Res. 2002;62:4123–31. |
es_ES |
dc.description.references |
Das K, Zhao Y, Sugiono M, Lau W, Tan PH, Cheng C. Differential expression of vascular endothelial growth factor165b in transitional cell carcinoma of the bladder. Urol Oncol. 2007;25:317–21. |
es_ES |
dc.description.references |
Woolard J, Wang WY, Bevan HS, et al. VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression. Cancer Res. 2004;64:7822–35. |
es_ES |
dc.description.references |
Manetti M, Guiducci S, Romano E, et al. Overexpression of VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, leads to insufficient angiogenesis in patients with systemic sclerosis. Circ Res. 2011;109:e14-e26. |
es_ES |
dc.description.references |
Salven P, Lymboussaki A, Heikkila P, et al. Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors. Am J Pathol. 1998;153:103–8. |
es_ES |
dc.description.references |
Nash AD, Baca M, Wright C, Scotney PD. The biology of vascular endothelial growth factor-B (VEGF-B). Pulm Pharmacol Ther. 2006;19:61–9. |
es_ES |
dc.description.references |
Mylona E, Alexandrou P, Giannopoulou I, et al. The prognostic value of vascular endothelial growth factors (VEGFs)-A and -B and their receptor, VEGFR-1, in invasive breast carcinoma. Gynecol Oncol. 2007;104:557–63. |
es_ES |
dc.description.references |
Wei SC, Tsao PN, Yu SC, et al. Placenta growth factor expression is correlated with survival of patients with colorectal cancer. Gut. 2005;54:666–72. |
es_ES |
dc.description.references |
Chen CN, Hsieh FJ, Cheng YM, et al. The significance of placenta growth factor in angiogenesis and clinical outcome of human gastric cancer. Cancer Lett. 2004;213:73–82. |
es_ES |
dc.description.references |
Matsumoto K, Suzuki K, Koike H, et al. Prognostic significance of plasma placental growth factor levels in renal cell cancer: an association with clinical characteristics and vascular endothelial growth factor levels. Anticancer Res. 2003;23:4953–8. |
es_ES |
dc.description.references |
Parr C, Watkins G, Boulton M, Cai J, Jiang WG. Placenta growth factor is over-expressed and has prognostic value in human breast cancer. Eur J Cancer. 2005;41:2819–27. |
es_ES |
dc.description.references |
Maae E, Olsen DA, Steffensen KD, et al. Prognostic impact of placenta growth factor and vascular endothelial growth factor A in patients with breast cancer. Breast Cancer Res Treat. 2012;133:257–65. |
es_ES |
dc.description.references |
Ho MC, Chen CN, Lee H, et al. Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocellular carcinoma. Cancer Lett. 2007;250:237–49. |
es_ES |
dc.description.references |
Zhang L, Chen J, Ke Y, Mansel RE, Jiang WG. Expression of placenta growth factor (PlGF) in non-small cell lung cancer (NSCLC) and the clinical and prognostic significance. World J Surg Oncol. 2005;3:68. |
es_ES |
dc.description.references |
Cheng SJ, Lee JJ, Kok SH, et al. Expression of placenta growth factor: an independent factor for prediction of progression and prognosis of oral cancer. Head Neck. 2010;32:1363–9. |
es_ES |
dc.description.references |
Woo IS, Park MJ, Byun JH, et al. Expression of placental growth factor gene in lung cancer. Tumour Biol. 2004;25:1–6. |
es_ES |
dc.description.references |
Neal JW. Histology matters: individualizing treatment in non-small cell lung cancer. Oncologist. 2010;15:3–5. |
es_ES |
dc.description.references |
Wheatley-Price P, Blackhall F, Lee SM, et al. The influence of sex and histology on outcomes in non-small-cell lung cancer: a pooled analysis of five randomized trials. Ann Oncol. 2010;21:2023–8. |
es_ES |
dc.description.references |
Langer CJ, Besse B, Gualberto A, Brambilla E, Soria JC. The evolving role of histology in the management of advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:5311–20. |
es_ES |
dc.description.references |
George ML, Tutton MG, Janssen F, et al. VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. Neoplasia. 2001;3:420–7. |
es_ES |
dc.description.references |
Charoenrat P, Rhys-Evans P, Eccles SA. Expression of vascular endothelial growth factor family members in head and neck squamous cell carcinoma correlates with lymph node metastasis. Cancer. 2001;92:556–68. |
es_ES |
dc.description.references |
Saintigny P, Kambouchner M, Ly M, et al. Vascular endothelial growth factor-C and its receptor VEGFR-3 in non-small-cell lung cancer: concurrent expression in cancer cells from primary tumour and metastatic lymph node. Lung Cancer. 2007;58:205–13. |
es_ES |
dc.description.references |
Bo C, Xiaopeng D, Chuanliang P, Xiaogang Z. Expression of vascular endothelial growth factors C and D correlates with lymphangiogenesis and lymph node metastasis in lung adenocarcinoma. Thorac Cardiovasc Surg. 2009;57:291–4. |
es_ES |
dc.description.references |
Nakamura Y, Yasuoka H, Tsujimoto M, et al. Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long-term follow-up. Clin Cancer Res. 2003;9:716–21. |
es_ES |
dc.description.references |
White JD, Hewett PW, Kosuge D, et al. Vascular endothelial growth factor-D expression is an independent prognostic marker for survival in colorectal carcinoma. Cancer Res. 2002;62:1669–75. |
es_ES |
dc.description.references |
Donnem T, Al Shibli K, Andersen S, Al Saad S, Busund LT, Bremnes RM. Combination of low vascular endothelial growth factor A (VEGF-A)/VEGF receptor 2 expression and high lymphocyte infiltration is a strong and independent favorable prognostic factor in patients with nonsmall cell lung cancer. Cancer. 2010;116:4318–25. |
es_ES |
dc.description.references |
Sands M, Howell K, Costello CM, McLoughlin P. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung. Respir Res. 2011;12:17. |
es_ES |
dc.description.references |
Moffat BA, Chen M, Kariaapper MS, et al. Inhibition of vascular endothelial growth factor (VEGF)-A causes a paradoxical increase in tumor blood flow and up-regulation of VEGF-D. Clin Cancer Res. 2006;12:1525–32. |
es_ES |