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. 2016 Jul 19;7(29):46253-46262.
doi: 10.18632/oncotarget.10086.

Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC)

Zhiyuan Tang  1 , Qin Shen  1 , Hao Xie  2 , Xiaoyu Zhou  1 , Jun Li  1 , Jian Feng  1 , Hua Liu  1 , Wei Wang  3 , Shu Zhang  3 , Songshi Ni  1
Affiliations

Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC)

Zhiyuan Tang et al. Oncotarget. .

Abstract

Fatty acid binding proteins (FABPs) are intracellular lipid-binding proteins that are involved in a variety of biological cellular processes, including tumorigenesis. In this study, we explored the expression pattern of FABP3 and FABP4 in non-small cell lung cancer (NSCLC) as well as their roles in prognosis. We determined mRNA expression of FABP3 and FABP4 in matched pairs of cancerous and non-cancerous fresh frozen tissues from 30 NSCLC patients. Tissue microarray immunohistochemical analysis (TMA-IHC) was applied to determine the protein expression of FABP3 and FABP4 in 281 cancerous and 121 matched adjacent non-cancerous tissue samples. Our results showed that both mRNA and protein expression of FABP3 and FABP4 were significantly higher in cancerous tissues when compared to non-cancerous tissues. Furthermore, high expression of FABP3 or FABP4 in NSCLC was significantly associated with advanced tumor node metastasis (TNM) stage and had a negative impact on the overall survival of NSCLC patients. Concurrent high expression of FABP3 and FABP4 was significantly related to TNM stage. In conclusion, our research demonstrated that high FABP3 or FABP4 expression had strong prognostic value for overall survival in NSCLC. Detection of FABP3 and FABP4 cooperatively was helpful to predict the prognosis of NSCLC.

Keywords: fatty acid binding protein-3(FABP3); fatty acid binding protein-4(FABP4); immunohistochemistry; non-small cell lung cancer; prognosis.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. FABP3 and FABP4 mRNA level was significantly higher in NSCLC cancerous tissues than in matched adjacent non-cancerous tissues
FABP3 and FABP4 mRNA was determined by qRT-PCR and relative quantification analysis by normalizing to GAPDH mRNA.
Figure 2
Figure 2. FABP3 and FABP4 protein detection in NSCLC tissues
FABP3 and FABP4 protein was determined by TMA-IHC, A1-A2. adenocarcinoma tissues, strong positive for FABP3 and FABP4 protein expression; B1-B2. squamous cell carcinoma tissues, positive for FABP3 and FABP4 protein expression; C1-C2. matched adjacent non-cancerous tissue samples, negative for FABP3 and FABP4 protein expression. A1, B1, and C1 were ×40 magnification (bar=500 μm), A2, B2, and C2 were ×400 magnification (bar=50 μm). Red arrows indicate positive FABP3 or FABP4 protein expression on cancerous cell cytoplasm, and green arrows indicate negative FABP3 or FABP4 protein expression on adjacent non-cancerous cells.
Figure 3
Figure 3. Survival curves of NSCLC patients by the Kaplan–Meier method and the log-rank test
A. FABP3+ NSCLC patients (green line) had significantly worse overall survival than FABP3- patients (blue line); B. FABP4+ NSCLC patients (green line) had significantly worse overall survival than FABP4- patients (blue line); C. FABP3+/FABP4+ NSCLC patients (green line) had significantly worse overall survival than FABP3+ or FABP4+ patients (blue line) and FABP3-/FABP4- NSCLC patients (yellow line); D. NSCLC patients with advanced TNM stage (green line for stage III and yellow line for stage II) had significantly worse overall survival than patients with TNM stage I (blue line).
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