Plasma neuron-specific enolase level as a prognostic marker in patients with non-small cell lung cancer receiving gefitinib

Inomata,Minehiko; Hayashi,Ryuji; Yamamoto,Azusa; Tokui,Kotaro; Taka,Chihiro; Okazawa,Seisuke; Kambara,Kenta; Suzuki,Kensuke; Ichikawa,Tomomi; Yamada,Toru; Miwa,Toshiro; Kashii,Tatsuhiko; Matsui,Shoko; Tobe,Kazuyuki; Imura,Johji

doi:10.3892/mco.2015.568

Plasma neuron-specific enolase level as a prognostic marker in patients with non-small cell lung cancer receiving gefitinib

Authors:
- Minehiko Inomata
- Ryuji Hayashi
- Azusa Yamamoto
- Kotaro Tokui
- Chihiro Taka
- Seisuke Okazawa
- Kenta Kambara
- Kensuke Suzuki
- Tomomi Ichikawa
- Toru Yamada
- Toshiro Miwa
- Tatsuhiko Kashii
- Shoko Matsui
- Kazuyuki Tobe
- Johji Imura
View Affiliations

Affiliations: First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Toyama 930‑0194, Japan, Department of Respiratory Medicine, Toyama Prefectural Central Hospital, Toyama, Toyama 930‑8550, Japan, Department of Medical Oncology, Toyama University Hospital, Toyama, Toyama 930‑0194, Japan, Health Administration Center, University of Toyama, Toyama, Toyama 930‑0194, Japan, Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Toyama 930‑0194, Japan
Published online on: May 14, 2015 https://doi.org/10.3892/mco.2015.568
Pages: 802-806

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Determination of the presence of epidermal growth factor receptor (EGFR) gene mutation is useful for predicting the efficacy of gefitinib. However, the survival rate following the initiation of treatment with gefitinib varies among individuals. A retrospective study was conducted to investigate the associations of the pretreatment serum pro‑gastrin‑releasing peptide (pro‑GRP) and plasma neuron‑specific enolase (NSE) levels to the patient survival rate following initiation of treatment with gefitinib in non‑small cell lung cancer (NSCLC) patients receiving gefitinib treatment. Patients with NSCLC harboring EGFR gene mutations who received gefitinib therapy between 2004 and 2012 were included in the study. Data from a total of 41 patients were analyzed. The serum pro‑GRP level was measured in 31 patients and the plasma NSE in 22 patients. The progression‑free survival (PFS) (P=0.013) and overall survival (OS) (P=0.014, log‑rank test) rates decreased as the plasma NSE level increased. Statistical analysis using a Cox proportional hazards regression model adjusted for age, gender, performance status (PS) and disease stage showed that higher NSE levels were associated with shorter PFS (P=0.021) and OS (P=0.0024). By contrast, no association was detected between the serum level of pro‑GRP and survival rate. The results suggest that pretreatment NSE measurement could be clinically useful in patients with NSCLC scheduled to receive gefitinib treatment.

View Figures

View References

1	Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, et al: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 361:947–957. 2009. View Article : Google Scholar : PubMed/NCBI
2	Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, et al: North-East Japan Study Group: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 362:2380–2388. 2010. View Article : Google Scholar : PubMed/NCBI
3	Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, et al: West Japan Oncology Group: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial. Lancet Oncol. 11:121–128. 2010. View Article : Google Scholar : PubMed/NCBI
4	Yano S, Wang W, Li Q, Matsumoto K, Sakurama H, Nakamura T, Ogino H, Kakiuchi S, Hanibuchi M, Nishioka Y, et al: Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res. 68:9479–9487. 2008. View Article : Google Scholar : PubMed/NCBI
5	Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, et al: Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 3:75ra262011. View Article : Google Scholar : PubMed/NCBI
6	Molina R, Auge JM, Filella X, Viñolas N, Alicarte J, Domingo JM and Ballesta AM: Pro-gastrin-releasing peptide (proGRP) in patients with benign and malignant diseases: Comparison with CEA, SCC, CYFRA 21-1 and NSE in patients with lung cancer. Anticancer Res. 25:1773–1778. 2005.PubMed/NCBI
7	van Zandwijk N, Jassem E, Bonfrer JM, Mooi WJ and van Tinteren H: Serum neuron-specific enolase and lactate dehydrogenase as predictors of response to chemotherapy and survival in non-small cell lung cancer. Semin Oncol. 19:(Suppl 2). 37–43. 1992.PubMed/NCBI
8	Diez M, Torres A, Ortega L, Maestro M, Hernando F, Gomez A, Picardo A, Granell J and Balibrea JL: Value of serum neuron-specific enolase in nonsmall cell lung cancer. Oncology. 50:127–131. 1993. View Article : Google Scholar : PubMed/NCBI
9	Pujol JL, Boher JM, Grenier J and Quantin X: Cyfra 21-1, neuron specific enolase and prognosis of non-small cell lung cancer: Prospective study in 621 patients. Lung Cancer. 31:221–231. 2001. View Article : Google Scholar : PubMed/NCBI
10	Ferrigno D, Buccheri G and Giordano C: Neuron-specific enolase is an effective tumour marker in non-small cell lung cancer (NSCLC). Lung Cancer. 41:311–320. 2003. View Article : Google Scholar : PubMed/NCBI
11	Viñolas N, Molina R, Galán MC, Casas F, Callejas MA, Filella X, Grau JJ, Ballesta AM and Estape J: Tumor markers in response monitoring and prognosis of non-small cell lung cancer: Preliminary report. Anticancer Res. 18:631–634. 1998.PubMed/NCBI
12	Rider CC and Taylor CB: Evidence for a new form of enolase in rat brain. Biochem Biophys Res Commun. 66:814–820. 1975. View Article : Google Scholar : PubMed/NCBI
13	Fiala O, Pesek M, Finek J, Benesova L, Minarik M, Bortlicek Z and Topolcan O: The role of neuron-specific enolase (NSE) and thymidine kinase (TK) levels in prediction of efficacy of EGFR-TKIs in patients with advanced-stage NSCLC. Anticancer Res. 34:5193–5198. 2014.PubMed/NCBI
14	Slodkowska J, Zych J, Szturmowicz M, Demkow U, Rowinska-Zakrzewska E and Roszkowski-Sliz K: Neuroendocrine phenotype of non-small cell lung carcinoma: Immunohistological evaluation and biochemical study. Int J Biol Markers. 20:217–226. 2005.PubMed/NCBI
15	Sørhaug S, Steinshamn S, Haaverstad R, Nordrum IS, Martinsen TC and Waldum HL: Expression of neuroendocrine markers in non-small cell lung cancer. APMIS. 115:152–163. 2007. View Article : Google Scholar : PubMed/NCBI
16	Broers JL, Rot MK, Oostendorp T, Huysmans A, Wagenaar SS, Wiersma-van Tilburg AJ, Vooijs GP and Ramaekers FC: Immunocytochemical detection of human lung cancer heterogeneity using antibodies to epithelial, neuronal, and neuroendocrine antigens. Cancer Res. 47:3225–3234. 1987.PubMed/NCBI
17	Pujol JL, Simony J, Laurent JC, Richer G, Mary H, Bousquet J, Godard P and Michel FB: Phenotypic heterogeneity studied by immunohistochemistry and aneuploidy in non-small cell lung cancers. Cancer Res. 49:2797–2802. 1989.PubMed/NCBI
18	Kibbelaar RE, Moolenaar KE, Michalides RJ, Van Bodegom PC, Vanderschueren RG, Wagenaar SS, Dingemans KP, Bitter-Suermann D, Dalesio O, Van Zandwijk N, et al: Neural cell adhesion molecule expression, neuroendocrine differentiation and prognosis in lung carcinoma. Eur J Cancer. 27:431–435. 1991. View Article : Google Scholar : PubMed/NCBI
19	Graziano SL, Mazid R, Newman N, Tatum A, Oler A, Mortimer JA, Gullo JJ, DiFino SM and Scalzo AJ: The use of neuroendocrine immunoperoxidase markers to predict chemotherapy response in patients with non-small-cell lung cancer. J Clin Oncol. 7:1398–1406. 1989.PubMed/NCBI
20	Pujol JL, Simony J, Demoly P, Charpentier R, Laurent JC, Daurès JP, Lehmann M, Guyot V, Godard P and Michel FB: Neural cell adhesion molecule and prognosis of surgically resected lung cancer. Am Rev Respir Dis. 148:1071–1075. 1993. View Article : Google Scholar : PubMed/NCBI
21	Hiroshima K, Iyoda A, Shibuya K, Toyozaki T, Haga Y, Fujisawa T and Ohwada H: Prognostic significance of neuroendocrine differentiation in adenocarcinoma of the lung. Ann Thorac Surg. 73:1732–1735. 2002. View Article : Google Scholar : PubMed/NCBI
22	Pelosi G, Pasini F, Sonzogni A, Maffini F, Maisonneuve P, Iannucci A, Terzi A, De Manzoni G, Bresaola E and Viale G: Prognostic implications of neuroendocrine differentiation and hormone production in patients with Stage I nonsmall cell lung carcinoma. Cancer. 97:2487–2497. 2003. View Article : Google Scholar : PubMed/NCBI
23	Howe MC, Chapman A, Kerr K, Dougal M, Anderson H and Hasleton PS: Neuroendocrine differentiation in non-small cell lung cancer and its relation to prognosis and therapy. Histopathology. 46:195–201. 2005. View Article : Google Scholar : PubMed/NCBI
24	Linnoila RI, Piantadosi S and Ruckdeschel JC: Impact of neuroendocrine differentiation in non-small cell lung cancer. The LCSG experience. Chest. 106:(Suppl 6). 367S–371S. 1994. View Article : Google Scholar : PubMed/NCBI
25	Hage R, Elbers HR, Brutel de la Rivière A and van den Bosch JM: Neural cell adhesion molecule expression: Prognosis in 889 patients with resected non-small cell lung cancer. Chest. 114:1316–1320. 1998. View Article : Google Scholar : PubMed/NCBI
26	Haimoto H, Takahashi Y, Koshikawa T, Nagura H and Kato K: Immunohistochemical localization of gamma-enolase in normal human tissues other than nervous and neuroendocrine tissues. Lab Invest. 52:257–263. 1985.PubMed/NCBI
27	Shibayama T, Ueoka H, Nishii K, Kiura K, Tabata M, Miyatake K, Kitajima T and Harada M: Complementary roles of pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) in diagnosis and prognosis of small-cell lung cancer (SCLC). Lung Cancer. 32:61–69. 2001. View Article : Google Scholar : PubMed/NCBI
28	Nisman B, Biran H, Ramu N, Heching N, Barak V and Peretz T: The diagnostic and prognostic value of ProGRP in lung cancer. Anticancer Res. 29:4827–4832. 2009.PubMed/NCBI