Skip to main content
Erschienen in: Clinical and Translational Oncology 5/2013

01.05.2013 | Research Article

Prognostic significance of NSE mRNA in advanced NSCLC treated with gefitinib

verfasst von: Y. Wang, D. Tang, A. Sui, W. Jiao, Y. Luo, M. Wang, R. Yang, Z. Wang, Y. Shen

Erschienen in: Clinical and Translational Oncology | Ausgabe 5/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Current knowledge of the prognostic biomarkers of advanced non-small cell lung cancer (NSCLC) treated with gefitinib is poor. NSE mRNA as a potential prognostic biomarker of the effectiveness of gefitinib treatment in NSCLC, especially in the Chinese population, needs to be further validated.

Patients and Methods

We retrospectively reviewed 168 advanced NSCLC patients treated with gefitinib between May 2006 and July 2010. NSE mRNA was measured using quantitative RT-PCR analysis for correlation with the clinical outcomes.

Results

We found that NSE mRNA expression was inversely correlated with sensitivity to gefitinib in NSCLC patients. Patients without elevated NSE mRNA had a more RR (CR + RR) 45.1 % than elevated 18.9 % (P = 0.0005). Moreover, the time to progression was 6.0 versus 4.2 months, respectively. Log-rank test was marginally significant (χ2 = 12.11, P = 0.0007) and Cox multivariate analysis revealed that NSE mRNA (HR = 3.076; 95 % CI 1.943–4.870; P < 0.0001) was an independent prognostic factor of NSCLC patients in the Chinese population.

Conclusion

For NSCLC patients treated with gefitinib, patients without elevated NSE mRNA had a better prognosis than those with elevated NSE mRNA. Pretreatment NSE mRNA holds great potential as a prognostic biomarker in advanced NSCLC. Therefore, it is proposed that NSE mRNA should be routinely detected to screen patients who are more likely to benefit from gefitinib-based treatment.
Literatur
1.
Zurück zum Zitat Christian WJ, Huang B, Rinehart J, Hopenhayn C (2011) Exploring geographic variation in lung cancer incidence in Kentucky using a spatial scan statistic: elevated risk in the Appalachian coal-mining region. Public Health Rep 126:789–796PubMed Christian WJ, Huang B, Rinehart J, Hopenhayn C (2011) Exploring geographic variation in lung cancer incidence in Kentucky using a spatial scan statistic: elevated risk in the Appalachian coal-mining region. Public Health Rep 126:789–796PubMed
2.
Zurück zum Zitat Armour AA, Watkins CL (2010) The challenge of targeting EGFR: experience with gefitinib in nonsmall cell lung cancer. Eur Respir Rev 19:186–196PubMedCrossRef Armour AA, Watkins CL (2010) The challenge of targeting EGFR: experience with gefitinib in nonsmall cell lung cancer. Eur Respir Rev 19:186–196PubMedCrossRef
3.
Zurück zum Zitat Maemondo M, Inoue A, Kobayashi K et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388PubMedCrossRef Maemondo M, Inoue A, Kobayashi K et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388PubMedCrossRef
4.
Zurück zum Zitat Favoni RE, Pattarozzi A, Lo Casto M et al (2010) Gefitinib targets EGFR dimerization and ERK1/2 phosphorylation to inhibit pleural mesothelioma cell proliferation. Curr Cancer Drug Targets 10:176–191PubMedCrossRef Favoni RE, Pattarozzi A, Lo Casto M et al (2010) Gefitinib targets EGFR dimerization and ERK1/2 phosphorylation to inhibit pleural mesothelioma cell proliferation. Curr Cancer Drug Targets 10:176–191PubMedCrossRef
5.
Zurück zum Zitat Ebert W, Muley T, Trainer C, Dienemann H, Drings P (2002) Comparison of changes in the NSE levels with clinical assessment in the therapy monitoring of patients with SCLC. Anticancer Res 22:1083–1089PubMed Ebert W, Muley T, Trainer C, Dienemann H, Drings P (2002) Comparison of changes in the NSE levels with clinical assessment in the therapy monitoring of patients with SCLC. Anticancer Res 22:1083–1089PubMed
6.
Zurück zum Zitat Satoh H, Ishikawa H, Kurishima K, Yamashita YT, Ohtsuka M, Sekizawa K (2002) Cut-off levels of NSE to differentiate SCLC from NSCLC. Oncol Rep 9:581–583 PubMed:11956631PubMed Satoh H, Ishikawa H, Kurishima K, Yamashita YT, Ohtsuka M, Sekizawa K (2002) Cut-off levels of NSE to differentiate SCLC from NSCLC. Oncol Rep 9:581–583 PubMed:11956631PubMed
7.
Zurück zum Zitat Gaafar RM, Surmont VF, Scagliotti GV et al (2011) A double-blind, randomised, placebo-controlled phase III intergroup study of gefitinib in patients with advanced NSCLC, non-progressing after first line platinum-based chemotherapy (EORTC 08021/ILCP 01/03). Eur J Cancer 47:2331–2340 PubMed:21802939PubMedCrossRef Gaafar RM, Surmont VF, Scagliotti GV et al (2011) A double-blind, randomised, placebo-controlled phase III intergroup study of gefitinib in patients with advanced NSCLC, non-progressing after first line platinum-based chemotherapy (EORTC 08021/ILCP 01/03). Eur J Cancer 47:2331–2340 PubMed:21802939PubMedCrossRef
8.
Zurück zum Zitat Kester MI, van der Flier WM, Visser A, Blankenstein MA, Scheltens P, Oudejans CB (2011) Decreased mRNA expression of CCL5 [RANTES] in Alzheimer’s disease blood samples. Clin Chem Lab Med. (PubMed:21942811) Kester MI, van der Flier WM, Visser A, Blankenstein MA, Scheltens P, Oudejans CB (2011) Decreased mRNA expression of CCL5 [RANTES] in Alzheimer’s disease blood samples. Clin Chem Lab Med. (PubMed:21942811)
9.
Zurück zum Zitat Reis PP, Waldron L, Goswami RS et al (2011) mRNA transcript quantification in archival samples using multiplexed, color-coded probes. BMC Biotechnol 11:46 PubMed:21549012PubMedCrossRef Reis PP, Waldron L, Goswami RS et al (2011) mRNA transcript quantification in archival samples using multiplexed, color-coded probes. BMC Biotechnol 11:46 PubMed:21549012PubMedCrossRef
10.
Zurück zum Zitat Fendri A, Kontos CK, Khabir A, Mokdad-Gargouri R, Scorilas A (2011) BCL2L12 is a novel biomarker for the prediction of short-term relapse in nasopharyngeal carcinoma. Mol Med 17:163–171 PubMed:21152697PubMedCrossRef Fendri A, Kontos CK, Khabir A, Mokdad-Gargouri R, Scorilas A (2011) BCL2L12 is a novel biomarker for the prediction of short-term relapse in nasopharyngeal carcinoma. Mol Med 17:163–171 PubMed:21152697PubMedCrossRef
11.
Zurück zum Zitat Schraml P, von Teichman A, Mihic-Probst D et al (2012) Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07. Oncol Rep 28:654–658 PubMed:22614944PubMed Schraml P, von Teichman A, Mihic-Probst D et al (2012) Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07. Oncol Rep 28:654–658 PubMed:22614944PubMed
12.
Zurück zum Zitat Yamaguchi S, Nishimura R, Yaegashi N et al (2012) Phase II study of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin followed by radical hysterectomy for bulky stage Ib2 to IIb, cervical squamous cell carcinoma: Japanese Gynecologic Oncology Group study (JGOG 1065). Oncol Rep 28:487–493 PubMed:22614251PubMed Yamaguchi S, Nishimura R, Yaegashi N et al (2012) Phase II study of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin followed by radical hysterectomy for bulky stage Ib2 to IIb, cervical squamous cell carcinoma: Japanese Gynecologic Oncology Group study (JGOG 1065). Oncol Rep 28:487–493 PubMed:22614251PubMed
13.
Zurück zum Zitat He JJ, Zhi K, Liu GF (2011) Predictive value of serum bone sialoprotein in patients with bone metastasis of non-small cell lung cancer. Onkologie 34:584–588 PubMed:22104154PubMedCrossRef He JJ, Zhi K, Liu GF (2011) Predictive value of serum bone sialoprotein in patients with bone metastasis of non-small cell lung cancer. Onkologie 34:584–588 PubMed:22104154PubMedCrossRef
14.
Zurück zum Zitat Shen X, Nair CK, Holmberg MJ et al (2011) Impact of left atrial volume in prediction of outcome after cardiac resynchronization therapy. Int J Cardiol 152:13–17 PubMed:20621370PubMedCrossRef Shen X, Nair CK, Holmberg MJ et al (2011) Impact of left atrial volume in prediction of outcome after cardiac resynchronization therapy. Int J Cardiol 152:13–17 PubMed:20621370PubMedCrossRef
15.
Zurück zum Zitat Xu N, Zhang X, Wang X et al (2012) FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells. Acta Pharmacol Sin 33:675–681 PubMed:22447226PubMedCrossRef Xu N, Zhang X, Wang X et al (2012) FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells. Acta Pharmacol Sin 33:675–681 PubMed:22447226PubMedCrossRef
16.
Zurück zum Zitat Chen YJ, Huang WC, Wei YL et al (2011) Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. PLoS ONE 6:e21428 PubMed:21731744PubMedCrossRef Chen YJ, Huang WC, Wei YL et al (2011) Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. PLoS ONE 6:e21428 PubMed:21731744PubMedCrossRef
17.
Zurück zum Zitat Rosell R, Perez-Roca L, Sanchez JJ et al (2009) Customized treatment in non-small-cell lung cancer based on EGFR mutations and BRCA1 mRNA expression. PLoS ONE 4:e5133 PubMed:19415121PubMedCrossRef Rosell R, Perez-Roca L, Sanchez JJ et al (2009) Customized treatment in non-small-cell lung cancer based on EGFR mutations and BRCA1 mRNA expression. PLoS ONE 4:e5133 PubMed:19415121PubMedCrossRef
18.
Zurück zum Zitat Judde JG, Rebucci M, Vogt N et al (2007) Gefitinib and chemotherapy combination studies in five novel human non small cell lung cancer xenografts. Evidence linking EGFR signaling to gefitinib antitumor response. Int J Cancer 120:1579–1590 PubMed:17205515PubMedCrossRef Judde JG, Rebucci M, Vogt N et al (2007) Gefitinib and chemotherapy combination studies in five novel human non small cell lung cancer xenografts. Evidence linking EGFR signaling to gefitinib antitumor response. Int J Cancer 120:1579–1590 PubMed:17205515PubMedCrossRef
19.
Zurück zum Zitat Reinmuth N, Thomas M, Meister M, Schnabel PA, Kreuter M (2010) Current data on predictive markers for anti-angiogenic therapy in thoracic tumours. Eur Respir J 36:915–924 PubMed:20889462PubMedCrossRef Reinmuth N, Thomas M, Meister M, Schnabel PA, Kreuter M (2010) Current data on predictive markers for anti-angiogenic therapy in thoracic tumours. Eur Respir J 36:915–924 PubMed:20889462PubMedCrossRef
20.
Zurück zum Zitat Toomey D, Smyth G, Condron C et al (2001) Immune function, telomerase, and angiogenesis in patients with primary, operable nonsmall cell lung carcinoma: tumor size and lymph node status remain the most important prognostic features. Cancer 92:2648–2657 PubMed:11745200PubMedCrossRef Toomey D, Smyth G, Condron C et al (2001) Immune function, telomerase, and angiogenesis in patients with primary, operable nonsmall cell lung carcinoma: tumor size and lymph node status remain the most important prognostic features. Cancer 92:2648–2657 PubMed:11745200PubMedCrossRef
21.
Zurück zum Zitat Zych J, Sakowicz A, Radzikowska E, Zaleska J, Rowinska-Zakrzewska E (1997) Neuron-specific enolase (NSE) serum level in non small cell lung cancer—can it be an indicator of tumour chemosensitivity? Rocz Akad Med Bialymst 42(Suppl 1):173–178 PubMed:9337535PubMed Zych J, Sakowicz A, Radzikowska E, Zaleska J, Rowinska-Zakrzewska E (1997) Neuron-specific enolase (NSE) serum level in non small cell lung cancer—can it be an indicator of tumour chemosensitivity? Rocz Akad Med Bialymst 42(Suppl 1):173–178 PubMed:9337535PubMed
22.
Zurück zum Zitat Smith B, Selby P, Southgate J, Pittman K, Bradley C, Blair GE (1991) Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction. Lancet 338:1227–1229 PubMed:1719320PubMedCrossRef Smith B, Selby P, Southgate J, Pittman K, Bradley C, Blair GE (1991) Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction. Lancet 338:1227–1229 PubMed:1719320PubMedCrossRef
23.
Zurück zum Zitat Belderbos J, Uitterhoeve L, van Zandwijk N et al (2007) Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972–22973). Eur J Cancer 43:114–121 PubMed:17084621PubMedCrossRef Belderbos J, Uitterhoeve L, van Zandwijk N et al (2007) Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972–22973). Eur J Cancer 43:114–121 PubMed:17084621PubMedCrossRef
24.
Zurück zum Zitat Chu XY, Hou XB, Song WA, Xue ZQ, Wang B, Zhang LB (2011) Diagnostic values of SCC, CEA, Cyfra21-1 and NSE for lung cancer in patients with suspicious pulmonary masses: a single center analysis. Cancer Biol Ther 11:995–1000 PubMed:21483235PubMedCrossRef Chu XY, Hou XB, Song WA, Xue ZQ, Wang B, Zhang LB (2011) Diagnostic values of SCC, CEA, Cyfra21-1 and NSE for lung cancer in patients with suspicious pulmonary masses: a single center analysis. Cancer Biol Ther 11:995–1000 PubMed:21483235PubMedCrossRef
25.
Zurück zum Zitat Tiseo M, Ardizzoni A, Cafferata MA et al (2008) Predictive and prognostic significance of neuron-specific enolase (NSE) in non-small cell lung cancer. Anticancer Res 28:507–513 PubMed:18383893PubMed Tiseo M, Ardizzoni A, Cafferata MA et al (2008) Predictive and prognostic significance of neuron-specific enolase (NSE) in non-small cell lung cancer. Anticancer Res 28:507–513 PubMed:18383893PubMed
26.
Zurück zum Zitat Dediu M (2011) Controversies in the management of advanced non-small cell lung cancer: maintenance therapy. J BUON 16:431–433 PubMed:22006744PubMed Dediu M (2011) Controversies in the management of advanced non-small cell lung cancer: maintenance therapy. J BUON 16:431–433 PubMed:22006744PubMed
27.
Zurück zum Zitat Rikova K, Guo A, Zeng Q et al (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131:1190–1203 PubMed:18083107PubMedCrossRef Rikova K, Guo A, Zeng Q et al (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131:1190–1203 PubMed:18083107PubMedCrossRef
28.
Zurück zum Zitat Heibeck TH, Ding SJ, Opresko LK et al (2009) An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells. J Proteome Res 8:3852–3861 PubMed:19534553PubMedCrossRef Heibeck TH, Ding SJ, Opresko LK et al (2009) An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells. J Proteome Res 8:3852–3861 PubMed:19534553PubMedCrossRef
29.
Zurück zum Zitat Jang SM, Kim JW, Kim CH, Kim D, Rhee S, Choi KH (2010) p19(ras) Represses proliferation of non-small cell lung cancer possibly through interaction with neuron-specific enolase (NSE). Cancer Lett 289:91–98 PubMed:19713034PubMedCrossRef Jang SM, Kim JW, Kim CH, Kim D, Rhee S, Choi KH (2010) p19(ras) Represses proliferation of non-small cell lung cancer possibly through interaction with neuron-specific enolase (NSE). Cancer Lett 289:91–98 PubMed:19713034PubMedCrossRef
30.
Zurück zum Zitat Grimminger PP, Schneider PM, Metzger R, et al (2010) The prognostic role of Bcl-2 mRNA expression in curatively resected non-small cell lung cancer (NSCLC). Lung Cancer 70:82–87 PubMed:20064672 Grimminger PP, Schneider PM, Metzger R, et al (2010) The prognostic role of Bcl-2 mRNA expression in curatively resected non-small cell lung cancer (NSCLC). Lung Cancer 70:82–87 PubMed:20064672
Metadaten
Titel
Prognostic significance of NSE mRNA in advanced NSCLC treated with gefitinib
verfasst von
Y. Wang
D. Tang
A. Sui
W. Jiao
Y. Luo
M. Wang
R. Yang
Z. Wang
Y. Shen
Publikationsdatum
01.05.2013
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 5/2013
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-012-0939-3

Weitere Artikel der Ausgabe 5/2013

Clinical and Translational Oncology 5/2013 Zur Ausgabe

Update Onkologie

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