Article Abstract

LAPTM4B-35 expression was correlated with favorable postoperation survival in pancreatic cancer patients

Authors: Can Cui, Jianhui Wu, Xiaojing Cheng, Liang Yan, Xiaoya Guan, Bin Dong, Min Zhao, Xiuyun Tian, Chunyi Hao


Background: Pancreatic cancer (PC) is malignant and lethal with its invasiveness and metastasis. Till now, it’s still very difficult to diagnose PC at its early stage due to lack of obvious symptoms. Therefore, there is an urgent need to find an efficient biomarker to help diagnose PC as early as possible. Lysosome-associated protein transmembrane 4 beta-35 (LAPTM4B-35) is a kind of transmembrane oncoprotein which has been proved to be overexpressed in a variety of solid tumors. Few studies have focused on the expression of LAPTM4B-35 and its function in PC patients. This study aimed to assess LAPTM4B-35 expression in PC and to investigate the relationship between LAPTM4B-35 expression with clinicopathological features and post-operation survival of PC patients.
Methods: We collected tumor tissues and paired non-cancerous tissues from 93 PC patients and evaluated LAPTM4B-35 expression through immunohistochemistry assay. And we also explored LAPTM4B-35 expression of mRNA and protein by means of reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR and Western blotting in PC cell lines and frozen tumor tissues. We used chi-squared test and Fisher’s exact test to evaluate the relationship between LAPTM4B-35 expression and clinicopathological factors. Kaplan-Meier survival analysis and Cox regression were used for survival analysis. A two-sided P value less than 0.05 was considered to be statistically significant.
Results: LAPTM4B-35 was found to be expressed in 60 of 93 (64.5%) tumor tissues and 7 of 93 (7.5%) paired non-cancerous tissues (P<0.001). LAPTM4B-35 expression was correlated with tumor differentiation (P=0.039), and LAPTM4B-35 expression was higher in tumor tissue of PC patients with moderate and well differentiation than those with poor differentiation. In addition, we also found a tendency that overexpression of LAPTM4B-35 was associated with more favorable clinicopathological features, including moderate and well differentiation, no lymph node metastasis, and early TNM stage and so on. In survival analysis, we found that patients with positive LAPTM4B-35 expression had a better post-operation survival than patients with negative LAPTM4B-35 expression (P=0.039). And in multivariate survival analysis, we also found that LAPTM4B-35 (positive vs. negative, P=0.029, OR =0.474, 95% CI: 0.242–0.927) and TNM stage (IV vs. I + II, P=0.001, OR =5.437, 95% CI: 1.940–15.237) were independent factors for post-operation survival of PC patients.
Conclusions: LAPTM4B-35 expression was correlated with favorable post-operation survival in PC patients. LAPTM4B-35 might act as a candidate biomarker for PC at its early stage.