LAPTM4B polymorphism is associated with non‑small cell lung cancer susceptibility and prognosis

Tang,Han; Tian,Hui; Yue,Weiming; Li,Lin; Li,Shuhai; Gao,Cun; Si,Libo; Qi,Lei; Lu,Ming; Hu,Wensi

doi:10.3892/or.2014.3116

LAPTM4B polymorphism is associated with non‑small cell lung cancer susceptibility and prognosis

Authors:
- Han Tang
- Hui Tian
- Weiming Yue
- Lin Li
- Shuhai Li
- Cun Gao
- Libo Si
- Lei Qi
- Ming Lu
- Wensi Hu
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Affiliations: Department of Thoracic Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: March 27, 2014 https://doi.org/10.3892/or.2014.3116
Pages: 2454-2460

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Abstract

Lysosome-associated protein transmembrane-4β (LAPTM4B) is a novel cancer-related gene that is upregulated in many tumors, and which plays important roles in carcinogenesis. It has two alleles, LAPTM4B*1 and LAPTM4B*2. LAPTM4B*1 contains only one copy of a 19-bp sequence in the first exon, whereas LAPTM4B*2 contains two tight tandem segments. Previous studies have shown that LAPTM4B*2 is a risk factor for susceptibility and prognosis of many tumors. The present study investigated the relationship between LAPTM4B polymorphism and non-small cell lung cancer (NSCLC) susceptibility and prognosis. We identified LAPTM4B genotypes with polymerase chain reaction (PCR) in peripheral blood samples. In the adjusted multivariate logistic regression analysis, we found that LAPTM4B*1/2, LAPTM4B*2/2 exhibited 1.48-fold [95% confidence interval (CI), 1.076-2.037] and 2.855-fold (95%CI, 1.722-4.734) increases in the risk of developing NSCLC compared with non-LAPTM4B*2 carriers. Furthermore, our results showed that overall survival time and disease-free survival time of patients with LAPTM4B*2 were significantly shorter than in patients carrying LAPTM4B*1 (P=0.001 and P=0.001, respectively). In addition, multivariate Cox regression analysis revealed that LAPTM4B*2 was also an independent prognostic factor for NSCLC. These results suggest that LAPTM4B polymorphisms may be a prospective marker for evaluating the risk and prognosis of NSCLC.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
2	Brognard J, Clark AS, Ni Y and Dennis PA: Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res. 61:3986–3997. 2001.PubMed/NCBI
3	Couraud S, Zalcman G, Milleron B, Morin F and Souquet PJ: Lung cancer in never smokers - a review. Eur J Cancer. 48:1299–1311. 2012. View Article : Google Scholar : PubMed/NCBI
4	Sun S, Schiller JH and Gazdar AF: Lung cancer in never smokers - a different disease. Nat Rev Cancer. 7:778–790. 2007. View Article : Google Scholar : PubMed/NCBI
5	Toh CK, Gao F, Lim WT, et al: Never-smokers with lung cancer: epidemiologic evidence of a distinct disease entity. J Clin Oncol. 24:2245–2251. 2006. View Article : Google Scholar : PubMed/NCBI
6	Liu X, Zhou R, Zhang Q, et al: Identification and characterization of LAPTM4B encoded by a human hepatocellular carcinoma-associated novel gene. Beijing Da Xue Xue Bao. 35:340–347. 2003.(In Chinese).
7	Shao GZ, Zhou RL, Zhang QY, et al: Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma. Oncogene. 22:5060–5069. 2003.PubMed/NCBI
8	Zhang G, Liang Y, Huang Y, Chen Y and Zhou R: Elevated lysosome-associated protein transmembrane-4β-35 is an independent prognostic marker in pancreatic carcinoma. J Int Med Res. 40:1275–1283. 2012.PubMed/NCBI
9	Zhou L, He XD, Chen J, et al: Overexpression of LAPTM4B-35 closely correlated with clinicopathological features and post-resectional survival of gallbladder carcinoma. Eur J Cancer. 43:809–815. 2007. View Article : Google Scholar : PubMed/NCBI
10	Yang Y, Yang H, McNutt MA, et al: LAPTM4B overexpression is an independent prognostic marker in ovarian carcinoma. Oncol Rep. 20:1077–1083. 2008.PubMed/NCBI
11	Meng F, Luo C, Hu Y, et al: Overexpression of LAPTM4B-35 in cervical carcinoma: a clinicopathologic study. Int J Gynecol Pathol. 29:587–593. 2011. View Article : Google Scholar : PubMed/NCBI
12	Wang S, Zhang QY and Zhou RL: Relationship between LAPTM4B gene polymorphism and susceptibility of primary liver cancer. Ann Oncol. 23:1864–1869. 2012.
13	Liu Y, Zhang QY, Qian N and Zhou RL: Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer. Ann Oncol. 18:311–316. 2007.
14	Cheng XJ, Xu W, Zhang QY and Zhou RL: Relationship between LAPTM4B gene polymorphism and susceptibility of colorectal and esophageal cancers. Ann Oncol. 19:527–532. 2008.
15	Yang H, Zhai G, Ji X, Xiong F, Su J and McNutt MA: Correlation of LAPTM4B polymorphisms with gallbladder carcinoma susceptibility in Chinese patients. Med Oncol. 29:2809–2813. 2012. View Article : Google Scholar : PubMed/NCBI
16	Xu Y, Liu Y, Zhou R, et al: LAPTM4B polymorphisms is associated with ovarian cancer susceptibility and its prognosis. Jpn J Clin Oncol. 42:413–419. 2012. View Article : Google Scholar
17	Li X, Kong X, Chen X, et al: LAPTM4B allele *2 is associated with breast cancer susceptibility and prognosis. PLoS One. 7:e449162012.
18	Deng LJ, Zhang QY, Liu B and Zhou RL: Relationship between LAPTM4B gene polymorphism and susceptibility of lung cancer. Beijing Da Xue Xue Bao. 37:302–305. 2005.(In Chinese).
19	Li C, Zhou Q, Wang Y, Chen X, Yang X and Zhu D: Relationship between LAPTM4B gene polymorphism and susceptibility of lung cancer. Zhongguo Fei Ai Za Zhi. 9:109–112. 2006.(In Chinese).
20	Zhai G, Yan K, Ji X, et al: LAPTM4B allele *2 is a marker of poor prognosis for gallbladder carcinoma. PLoS One. 7:e452902012.
21	Yang H, Zhai G, Ji X, Xiong F, Su J and McNutt MA: LAPTM4B allele *2 is a marker of poor prognosis following hepatic tumor resection for hepatocellular carcinoma. PLoS One. 7:e349842012.
22	Meng F, Li H, Zhou R, Luo C, Hu Y and Lou G: LAPTM4B gene polymorphism and endometrial carcinoma risk and prognosis. Biomarkers. 18:136–143. 2013. View Article : Google Scholar
23	Sobin LGM and Wittekind C: TNM Classification of Malignant Tumours. 7th edition. Wiley-Blackwell; New York: 2010
24	Kasper G, Vogel A, Klaman I, et al: The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression. Cancer Lett. 224:93–103. 2005. View Article : Google Scholar : PubMed/NCBI
25	Xiao M, Jia S, Wang H, Wang J, Huang Y and Li Z: Overexpression of LAPTM4B: an independent prognostic marker in breast cancer. J Cancer Res Clin Oncol. 139:661–667. 2013.
26	Kang Y, Yin M, Jiang W, et al: Overexpression of LAPTM4B-35 is associated with poor prognosis in colorectal carcinoma. Am J Surg. 204:677–683. 2012. View Article : Google Scholar : PubMed/NCBI
27	Yin M, Lou C, Zhang W, et al: LAPTM4B overexpression is a novel independent prognostic marker for metastatic ovarian tumors. Int J Gynecol Cancer. 22:54–62. 2012. View Article : Google Scholar : PubMed/NCBI
28	Liu X, Xiong F, Wei X, Yang H and Zhou R: LAPTM4B-35, a novel tetratransmembrane protein and its PPRP motif play critical roles in proliferation and metastatic potential of hepatocellular carcinoma cells. Cancer Sci. 100:2335–2340. 2009. View Article : Google Scholar : PubMed/NCBI
29	Yang H, Xiong F, Wei X, Yang Y, McNutt MA and Zhou R: Overexpression of LAPTM4B-35 promotes growth and metastasis of hepatocellular carcinoma in vitro and in vivo. Cancer Lett. 294:236–244. 2010. View Article : Google Scholar : PubMed/NCBI
30	Zhou L, He XD, Yu JC, Zhou RL, Shan Y and Rui JA: Overexpression of LAPTM4B-35 attenuates epirubucin-induced apoptosis of gallbladder carcinoma GBC-SD cells. Surgery. 150:25–31. 2011. View Article : Google Scholar : PubMed/NCBI
31	Li L, Wei XH, Pan YP, et al: LAPTM4B: a novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling. Oncogene. 29:5785–5795. 2010. View Article : Google Scholar : PubMed/NCBI
32	Zhang M, Xu JJ, Zhou RL and Zhang QY: cAMP responsive element binding protein-1 is a transcription factor of lysosomal-associated protein transmembrane-4 beta in human breast cancer cells. PLoS One. 8:e575202013. View Article : Google Scholar