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Erschienen in: Tumor Biology 10/2015

01.10.2015 | Research Article

Lysosome-associated protein transmembrane-4β-35 is a novel independent prognostic factor in small cell lung cancer

verfasst von: Man Qiao, Guohua Hu

Erschienen in: Tumor Biology | Ausgabe 10/2015

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Abstract

The lysosome-associated protein transmembrane-4β-35 (LAPTM4B-35) protein has been indicated to be involved in solid tumors, while its role in small cell lung cancer (SCLC) remains unknown. The aim of this study is to investigate the LAPTM4B-35 protein expression and its clinical and prognostic role in SCLC patients. A total of 88 SCLC patients who underwent radical surgery between 2002 and 2010 were enrolled in the study. The level of messenger RNA (mRNA) and protein was detected from the fresh paired tumor specimens and adjacent normal tissues. The clinicopathological and survival data were collected. And the relationship between LAPTM4B-35 and clinicopathological features was analyzed. The prognostic value of LAPTM4B-35 for SCLC was investigated by univariate and multivariate analyses. The LAPTM4B-35 was overexpressed significantly in SCLC cancer tissues. The elevated protein expression was correlated strongly with clinical stage (p = 0.012) and tumor recurrence (p = 0.023). The 5-year overall survival and disease-free survival (DFS) were significantly worse in the patients with high LAPTM4B-35 level. Multivariate Cox analysis indicated that high LAPTM4B-35 expression was an independent prognostic factor for overall survival (OS) and DFS (p = 0.017 vs p = 0.011). LAPTM4B-35 overexpression was an independent factor in SCLC prognosis, which may be considered a potential useful marker in defining the SCLC prognosis.
Literatur
1.
2.
Zurück zum Zitat Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24:4539–44.CrossRefPubMed Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24:4539–44.CrossRefPubMed
3.
Zurück zum Zitat Tartarone A, Lerose R, Ardito R, Troiani L, Tedesco B, Bozza G, et al. Long-term survival in small cell lung cancer: a case report and review of the literature. Future Oncol. 2014;10:523–8.CrossRefPubMed Tartarone A, Lerose R, Ardito R, Troiani L, Tedesco B, Bozza G, et al. Long-term survival in small cell lung cancer: a case report and review of the literature. Future Oncol. 2014;10:523–8.CrossRefPubMed
4.
Zurück zum Zitat Kalemkerian GP. Advances in pharmacotherapy of small cell lung cancer. Expert Opin Pharmacother. 2014;15:2385–96.CrossRefPubMed Kalemkerian GP. Advances in pharmacotherapy of small cell lung cancer. Expert Opin Pharmacother. 2014;15:2385–96.CrossRefPubMed
5.
Zurück zum Zitat Pillai RN, Owonikoko TK. Small cell lung cancer: therapies and targets. Semin Oncol. 2014;41:133–42.CrossRefPubMed Pillai RN, Owonikoko TK. Small cell lung cancer: therapies and targets. Semin Oncol. 2014;41:133–42.CrossRefPubMed
6.
Zurück zum Zitat Osterlind K, Andersen PK. Prognostic factors in small cell lung cancer: multivariate model based on 778 patients treated with chemotherapy with or without irradiation. Cancer Res. 1986;46:4189–94.PubMed Osterlind K, Andersen PK. Prognostic factors in small cell lung cancer: multivariate model based on 778 patients treated with chemotherapy with or without irradiation. Cancer Res. 1986;46:4189–94.PubMed
7.
Zurück zum Zitat Paesmans M, Sculier JP, Lecomte J, Thiriaux J, Libert P, Sergysels R, et al. Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years. Cancer. 2000;89:523–33.CrossRefPubMed Paesmans M, Sculier JP, Lecomte J, Thiriaux J, Libert P, Sergysels R, et al. Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years. Cancer. 2000;89:523–33.CrossRefPubMed
8.
Zurück zum Zitat Li J, Dai CH, Chen P, Wu JN, Bao QL, Qiu H, et al. Survival and prognostic factors in small cell lung cancer. Med Oncol. 2010;27:73–81.CrossRefPubMed Li J, Dai CH, Chen P, Wu JN, Bao QL, Qiu H, et al. Survival and prognostic factors in small cell lung cancer. Med Oncol. 2010;27:73–81.CrossRefPubMed
9.
Zurück zum Zitat Bremnes RM, Sundstrom S, Aasebo U, Kaasa S, Hatlevoll R, Aamdal S. The value of prognostic factors in small cell lung cancer: results from a randomised multicenter study with minimum 5 year follow-up. Lung Cancer. 2003;39:303–13.CrossRefPubMed Bremnes RM, Sundstrom S, Aasebo U, Kaasa S, Hatlevoll R, Aamdal S. The value of prognostic factors in small cell lung cancer: results from a randomised multicenter study with minimum 5 year follow-up. Lung Cancer. 2003;39:303–13.CrossRefPubMed
10.
Zurück zum Zitat Ustuner Z, Saip P, Yasasever V, Vural B, Yazar A, Bal C, et al. Prognostic and predictive value of vascular endothelial growth factor and its soluble receptors, VEGFR-1 and VEGFR-2 levels in the sera of small cell lung cancer patients. Med Oncol. 2008;25:394–9.CrossRefPubMed Ustuner Z, Saip P, Yasasever V, Vural B, Yazar A, Bal C, et al. Prognostic and predictive value of vascular endothelial growth factor and its soluble receptors, VEGFR-1 and VEGFR-2 levels in the sera of small cell lung cancer patients. Med Oncol. 2008;25:394–9.CrossRefPubMed
11.
Zurück zum Zitat Wang X, Jiang R, Li K. Prognostic significance of pretreatment laboratory parameters in combined small-cell lung cancer. Cell Biochem Biophys. 2014;69:633–40.CrossRefPubMed Wang X, Jiang R, Li K. Prognostic significance of pretreatment laboratory parameters in combined small-cell lung cancer. Cell Biochem Biophys. 2014;69:633–40.CrossRefPubMed
12.
Zurück zum Zitat Wu C, Li F, Jiao SC. Prognostic factors for survival of patients with extensive stage small cell lung cancer—a retrospective single institution analysis. Asian Pac J Cancer Prev. 2012;13:4959–62.CrossRefPubMed Wu C, Li F, Jiao SC. Prognostic factors for survival of patients with extensive stage small cell lung cancer—a retrospective single institution analysis. Asian Pac J Cancer Prev. 2012;13:4959–62.CrossRefPubMed
13.
Zurück zum Zitat Liu XR, Zhou RL, Zhang QY, Zhang Y, Jin YY, Lin M, et al. Structure analysis and expressions of a novel tetratransmembrane protein, lysosoma-associated protein transmembrane 4 beta associated with hepatocellular carcinoma. World J Gastroenterol. 2004;10:1555–9.CrossRefPubMedPubMedCentral Liu XR, Zhou RL, Zhang QY, Zhang Y, Jin YY, Lin M, et al. Structure analysis and expressions of a novel tetratransmembrane protein, lysosoma-associated protein transmembrane 4 beta associated with hepatocellular carcinoma. World J Gastroenterol. 2004;10:1555–9.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Shao GZ, Zhou RL, Zhang QY, Zhang Y, Liu JJ, Rui JA, et al. Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma. Oncogene. 2003;22:5060–9.CrossRefPubMed Shao GZ, Zhou RL, Zhang QY, Zhang Y, Liu JJ, Rui JA, et al. Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma. Oncogene. 2003;22:5060–9.CrossRefPubMed
15.
Zurück zum Zitat Liu L, Xu X, Jing L, Zhou G, Cao Z, Han Y, et al. Lysosomal-associated protein transmembrane 4 beta-35 overexpression is a novel independent prognostic marker for gastric carcinoma. PLoS One. 2015;10:e0118026.CrossRefPubMedPubMedCentral Liu L, Xu X, Jing L, Zhou G, Cao Z, Han Y, et al. Lysosomal-associated protein transmembrane 4 beta-35 overexpression is a novel independent prognostic marker for gastric carcinoma. PLoS One. 2015;10:e0118026.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Zhang H, Wei Q, Liu R, Qi S, Liang P, Qi C, et al. Overexpression of LAPTM4B-35: a novel marker of poor prognosis of prostate cancer. PLoS One. 2014;9:e91069.CrossRefPubMedPubMedCentral Zhang H, Wei Q, Liu R, Qi S, Liang P, Qi C, et al. Overexpression of LAPTM4B-35: a novel marker of poor prognosis of prostate cancer. PLoS One. 2014;9:e91069.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Zhang G, Liang Y, Huang Y, Chen Y, Zhou R. Elevated lysosome-associated protein transmembrane-4beta-35 is an independent prognostic marker in pancreatic carcinoma. J Int Med Res. 2012;40:1275–83.CrossRefPubMed Zhang G, Liang Y, Huang Y, Chen Y, Zhou R. Elevated lysosome-associated protein transmembrane-4beta-35 is an independent prognostic marker in pancreatic carcinoma. J Int Med Res. 2012;40:1275–83.CrossRefPubMed
18.
Zurück zum Zitat Kang Y, Yin M, Jiang W, Zhang H, Xia B, Xue Y, et al. Overexpression of LAPTM4B-35 is associated with poor prognosis in colorectal carcinoma. Am J Surg. 2012;204:677–83.CrossRefPubMed Kang Y, Yin M, Jiang W, Zhang H, Xia B, Xue Y, et al. Overexpression of LAPTM4B-35 is associated with poor prognosis in colorectal carcinoma. Am J Surg. 2012;204:677–83.CrossRefPubMed
19.
Zurück zum Zitat Tang H, Tian H, Yue W, Li L, Li S, Gao C, et al. Overexpression of LAPTM4B is correlated with tumor angiogenesis and poor prognosis in non-small cell lung cancer. Med Oncol. 2014;31:974.CrossRefPubMed Tang H, Tian H, Yue W, Li L, Li S, Gao C, et al. Overexpression of LAPTM4B is correlated with tumor angiogenesis and poor prognosis in non-small cell lung cancer. Med Oncol. 2014;31:974.CrossRefPubMed
20.
Zurück zum Zitat van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet. 2011;378:1741–55.CrossRefPubMed van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet. 2011;378:1741–55.CrossRefPubMed
21.
Zurück zum Zitat Adelstein DJ, Tomashefski Jr JF, Snow NJ, Horrigan TP, Hines JD. Mixed small cell and non-small cell lung cancer. Chest. 1986;89:699–704.CrossRefPubMed Adelstein DJ, Tomashefski Jr JF, Snow NJ, Horrigan TP, Hines JD. Mixed small cell and non-small cell lung cancer. Chest. 1986;89:699–704.CrossRefPubMed
22.
Zurück zum Zitat Babakoohi S, Fu P, Yang M, Linden PA, Dowlati A. Combined SCLC clinical and pathologic characteristics. Clin Lung Cancer. 2013;14:113–9.CrossRefPubMed Babakoohi S, Fu P, Yang M, Linden PA, Dowlati A. Combined SCLC clinical and pathologic characteristics. Clin Lung Cancer. 2013;14:113–9.CrossRefPubMed
23.
Zurück zum Zitat Mangum MD, Greco FA, Hainsworth JD, Hande KR, Johnson DH. Combined small-cell and non-small-cell lung cancer. J Clin Oncol. 1989;7:607–12.CrossRefPubMed Mangum MD, Greco FA, Hainsworth JD, Hande KR, Johnson DH. Combined small-cell and non-small-cell lung cancer. J Clin Oncol. 1989;7:607–12.CrossRefPubMed
24.
Zurück zum Zitat Nicholson SA, Beasley MB, Brambilla E, Hasleton PS, Colby TV, Sheppard MN, et al. Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens. Am J Surg Pathol. 2002;26:1184–97.CrossRefPubMed Nicholson SA, Beasley MB, Brambilla E, Hasleton PS, Colby TV, Sheppard MN, et al. Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens. Am J Surg Pathol. 2002;26:1184–97.CrossRefPubMed
25.
Zurück zum Zitat Xiao M, Jia S, Wang H, Wang J, Huang Y, Li Z. Overexpression of LAPTM4B: an independent prognostic marker in breast cancer. J Cancer Res Clin Oncol. 2013;139:661–7.CrossRefPubMed Xiao M, Jia S, Wang H, Wang J, Huang Y, Li Z. Overexpression of LAPTM4B: an independent prognostic marker in breast cancer. J Cancer Res Clin Oncol. 2013;139:661–7.CrossRefPubMed
26.
Zurück zum Zitat Yin M, Li C, Li X, Lou G, Miao B, Liu X, et al. Over-expression of LAPTM4B is associated with poor prognosis and chemotherapy resistance in stages III and IV epithelial ovarian cancer. J Surg Oncol. 2011;104:29–36.CrossRefPubMed Yin M, Li C, Li X, Lou G, Miao B, Liu X, et al. Over-expression of LAPTM4B is associated with poor prognosis and chemotherapy resistance in stages III and IV epithelial ovarian cancer. J Surg Oncol. 2011;104:29–36.CrossRefPubMed
27.
Zurück zum Zitat Zhou L, He XD, Chen J, Cui QC, Qu Q, Rui JA, et al. Overexpression of LAPTM4B-35 closely correlated with clinicopathological features and post-resectional survival of gallbladder carcinoma. Eur J Cancer. 2007;43:809–15.CrossRefPubMed Zhou L, He XD, Chen J, Cui QC, Qu Q, Rui JA, et al. Overexpression of LAPTM4B-35 closely correlated with clinicopathological features and post-resectional survival of gallbladder carcinoma. Eur J Cancer. 2007;43:809–15.CrossRefPubMed
28.
Zurück zum Zitat Meng F, Luo C, Hu Y, Yin M, Lin M, Lou G, et al. Overexpression of LAPTM4B-35 in cervical carcinoma: a clinicopathologic study. Int J Gynecol Pathol. 2010;29:587–93.CrossRefPubMed Meng F, Luo C, Hu Y, Yin M, Lin M, Lou G, et al. Overexpression of LAPTM4B-35 in cervical carcinoma: a clinicopathologic study. Int J Gynecol Pathol. 2010;29:587–93.CrossRefPubMed
29.
Zurück zum Zitat Yang H, Xiong F, Wei X, Yang Y, McNutt MA, Zhou R. Overexpression of LAPTM4B-35 promotes growth and metastasis of hepatocellular carcinoma in vitro and in vivo. Cancer Lett. 2010;294:236–44.CrossRefPubMed Yang H, Xiong F, Wei X, Yang Y, McNutt MA, Zhou R. Overexpression of LAPTM4B-35 promotes growth and metastasis of hepatocellular carcinoma in vitro and in vivo. Cancer Lett. 2010;294:236–44.CrossRefPubMed
30.
Zurück zum Zitat Zhou L, He XD, Yu JC, Zhou RL, Yang H, Qu Q, et al. Overexpression of LAPTM4B promotes growth of gallbladder carcinoma cells in vitro. Am J Surg. 2010;199:515–21.CrossRefPubMed Zhou L, He XD, Yu JC, Zhou RL, Yang H, Qu Q, et al. Overexpression of LAPTM4B promotes growth of gallbladder carcinoma cells in vitro. Am J Surg. 2010;199:515–21.CrossRefPubMed
31.
Zurück zum Zitat Yang H, Zhai G, Ji X, Xiong F, Su J, McNutt MA. LAPTM4B allele *2 is a marker of poor prognosis following hepatic tumor resection for hepatocellular carcinoma. PLoS One. 2012;7:e34984.CrossRefPubMedPubMedCentral Yang H, Zhai G, Ji X, Xiong F, Su J, McNutt MA. LAPTM4B allele *2 is a marker of poor prognosis following hepatic tumor resection for hepatocellular carcinoma. PLoS One. 2012;7:e34984.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Li Y, Zhang Q, Tian R, Wang Q, Zhao JJ, Iglehart JD, et al. Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells. Cancer Res. 2011;71:7481–9.CrossRefPubMedPubMedCentral Li Y, Zhang Q, Tian R, Wang Q, Zhao JJ, Iglehart JD, et al. Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells. Cancer Res. 2011;71:7481–9.CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Li L, Wei XH, Pan YP, Li HC, Yang H, He QH, et al. LAPTM4B: a novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling. Oncogene. 2010;29:5785–95.CrossRefPubMed Li L, Wei XH, Pan YP, Li HC, Yang H, He QH, et al. LAPTM4B: a novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling. Oncogene. 2010;29:5785–95.CrossRefPubMed
34.
Zurück zum Zitat Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Desmedt C, et al. Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nat Med. 2010;16:214–8.CrossRefPubMedPubMedCentral Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Desmedt C, et al. Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nat Med. 2010;16:214–8.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Zhou L, He XD, Yu JC, Zhou RL, Shan Y, Rui JA. Overexpression of LAPTM4B-35 attenuates epirubucin-induced apoptosis of gallbladder carcinoma GBC-SD cells. Surgery. 2011;150:25–31.CrossRefPubMed Zhou L, He XD, Yu JC, Zhou RL, Shan Y, Rui JA. Overexpression of LAPTM4B-35 attenuates epirubucin-induced apoptosis of gallbladder carcinoma GBC-SD cells. Surgery. 2011;150:25–31.CrossRefPubMed
Metadaten
Titel
Lysosome-associated protein transmembrane-4β-35 is a novel independent prognostic factor in small cell lung cancer
verfasst von
Man Qiao
Guohua Hu
Publikationsdatum
01.10.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 10/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3467-2

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