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A High Level of TM4SF5 Is Associated with Human Esophageal Cancer Progression and Poor Patient Survival

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Abstract

Purpose

We investigated expression of TM4SF5 and its involvement in human esophageal cancer (HEC).

Methods

We analyzed TM4SF5 expression in normal esophageal epithelial cells (HEEC), in four HEC cell lines, and in 20 HEC clinical tissue samples and matched nontumor samples. The effect of TM4SF5 on HEC cell proliferation and metastasis and invasion was assessed, and the relationship between TM4SF5 and integrin β1 was determined. Finally, TM4SF5 and integrin β1 expression were further examined by use of immunohistochemistry (IHC) and tissue microarray analysis, and the prognostic use of TM4SF5 and integrin β1 in HEC was evaluated.

Results

TM4SF5 was more highly expressed in HEC cells and in HEC tissues than in HEEC and matched nontumor tissues. Down-regulation of TM4SF5 in KYSE150 cells reduced cell proliferation and metastasis and invasion whereas metastasis and invasion by KYSE510 increased after TM4SF5 cDNA transfection. In HEC cells, TM4SF5 formed a complex with integrin β1, and interference with integrin β1 in KYSE510-TM4SF5 cells markedly inhibited cell invasion on laminin 5. Our findings also showed that TM4SF5 and integrin β1 overexpression correlated with low differentiation and high stage (p < 0.05, respectively). Postoperative 5-year overall survival of patients with TM4SF5low and/or integrin β1low was higher than for patients with TM4SF5high and/or integrin β1high. Multivariate analysis demonstrated that TM4SF5 and integrin β1 co-overexpression was an independent prognostic marker for HEC.

Conclusion

TM4SF5 is positively associated with HEC invasiveness. The combination of TM4SF5 with integrin β1 could potentially serve as a novel marker for predicting HEC prognosis.

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Abbreviations

HEC:

Human esophageal cancer

ESCC:

Esophageal squamous cell carcinoma

HEEC:

Human normal esophageal epithelial cells

TM4SF5:

Four-transmembrane L6 family member 5

TMA:

Tissue microarray

IHC:

Immunohistochemistry

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

RT-PCR:

Reverse transcription-polymerase chain reaction

OS:

Overall survival

TEM:

Tetraspanin-enriched membrane microdomain

DMEM:

Dulbecco’s modified Eagle’s medium

HCC:

Hepatocellular carcinoma

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81260321, 309603381) and the National Natural Science Foundation of Hainan Province (No. 811206).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People’s Republic of China

    Yong-bing Wu, Dong-liang Yu, Xiao-qiang Zhang, Xiang Long, Shu-qiang Zhu, Jiang-liang Zhou & Jian-jun Xu

  2. Department of Pathology, Hainan Medical University, Haikou, 571101, Hainan, People’s Republic of China

    You-sheng Huang

  3. Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China

    Ya-ping Xu

  4. Department of Gynecology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China

    Yu-fang Sun

Authors
  1. Yong-bing Wu
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  2. You-sheng Huang
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  3. Ya-ping Xu
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  4. Yu-fang Sun
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  5. Dong-liang Yu
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  6. Xiao-qiang Zhang
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  7. Xiang Long
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  8. Shu-qiang Zhu
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  9. Jiang-liang Zhou
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  10. Jian-jun Xu
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Corresponding author

Correspondence to Jian-jun Xu.

Additional information

Yong-bing Wu, You-sheng Huang, Ya-ping Xu, and Yu-fang Sun contributed equally to the work.

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Wu, Yb., Huang, Ys., Xu, Yp. et al. A High Level of TM4SF5 Is Associated with Human Esophageal Cancer Progression and Poor Patient Survival. Dig Dis Sci 58, 2623–2633 (2013). https://doi.org/10.1007/s10620-013-2690-1

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  • DOI: https://doi.org/10.1007/s10620-013-2690-1

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