Clinical significance of LAMB3 and COL7A1 mRNA in esophageal squamous cell carcinoma

https://doi.org/10.1016/j.ejso.2008.01.025Get rights and content

Abstract

Aims

LAMB3 and COL7A1 genes code for the laminin-5β3 chain and type VII collagen, respectively. They constitute the major components of the basement membrane zone. The aim of the current study was to clarify the clinical significance of LAMB3 and COL7A1 mRNA expression in esophageal squamous cell carcinoma (ESC).

Methods

We quantitated the expression of LAMB3 mRNA and COL7A1 mRNA in malignant esophageal tissues (T) and corresponding normal tissues (N) by real-time quantitative reverse transcription-polymerase chain reaction assays. The clinicopathologic significance of LAMB3 and COL7A1 expression was also determined. Paired T and N tissues were obtained from 66 patients who underwent curative esophagectomy.

Results

The expression levels of LAMB3 and COL7A1 mRNAs were higher in malignant tissues than in the corresponding normal tissues. The level of LAMB3 expression was significantly correlated with the depth of invasion and venous invasion (p = 0.007 and 0.001, respectively). COL7A1 expression was significantly correlated with depth of tumor invasion and lymphatic invasion (p = 0.046, 0.013, respectively). The five-year survival rate was better in the 22 patients with relatively low expression of both LAMB3 and COL7A1 in comparison with the other 44 cases (p < 0.05).

Conclusion

The evaluation of LAMB3 and COL7A1 mRNA expression is useful for predicting the malignant properties of ESC and may prove valuable in predicting the future course of the disease.

Introduction

Esophageal squamous cell carcinoma (ESC) is one of the most aggressive carcinomas in the gastrointestinal tract. We previously performed an oligomicroarray analysis of primary esophageal cancer to identify genes which were overexpressed in malignant tissue compared to corresponding normal tissue.1 Consequently, several interesting genes were identified, two of which, LAMB3 and COL7A1, had not been evaluated previously in ESC.

LAMB3 codes for one of the trimeric proteins constituting Laminin-5. The α3, β3, and γ2 chains of laminin-5 are encoded by three distinct genes, LAMA3, LAMB3, and LAMC2, respectively.2 Laminin-5 is an extracellular matrix protein secreted by cultured human keratinocytes,3 and is one of the major factors stimulating the invasive and metastatic abilities of several types of tumor cells4, 5 in the colon,6 pancreas,7 lung,8 stomach,9 prostate10 and esophagus.11, 12

On the other hand, type VII collagen, which is encoded by the COL7A1 gene, is the major component of anchoring fibres in the basement membrane.13 Dystrophic epidermolysis bullusa, an incurable, potentially fatal skin disease, and a family of inherited mechano-bullous disorders, are caused by mutation of COL7A1.

We previously reported that the staining pattern of basement membrane components in esophageal squamous cell carcinoma did not correlate with the survival rate, but did correlate with the histologic differentiation of epithelial organization.14 A recent study by Felix et al. showed that loss of laminin and collagen IV was associated with carcinogenesis or progression in human G–I tract cancer.15 Therefore, we have focused on cancer-specific genes which are associated with proteins constituting the basement membrane These proteins are required in many important biological process, including tissue remodeling and tumor invasion.16 The aim of this study was to quantitate the expression of LAMB3 mRNA and COL7A1 mRNA in malignant and normal esophageal tissues and to determine whether the expression status was associated with any clinicopathologic parameters of ESC and the prognosis of ESC patients.

Section snippets

Patients

This study assessed 66 patients with ESC (62 men and 4 women) who underwent esophagectomy with lymph node dissection between 1998 and 2005 at Kagoshima University Hospital and the Medical Institute of Bioregulation Hospital, Kyushu University, Japan. The median age of the patients was 65 years (range 47–87 years). Specimens of cancer tissues and non-cancerous adjacent tissues were collected from patients after informed consent had been obtained in accordance with the institutional guidelines of

Expression of LAMB3 mRNA in clinical tissues from ESC patients

Most patients (58 of 66, (87.9%)) showed higher expression levels of LAMB3 mRNA in cancerous tissues than in non-cancerous tissues by real-time quantitative reverse transcription-PCR. The mean expression level of LAMB3 mRNA in tumor tissues was 2.103 ± 3.061 (mean ± SD), which was significantly higher than the value obtained from the corresponding normal tissues (0.362 ± 0.617, p < 0.0001).

The clinicopathologic significance of LAMB3 mRNA expression in ESC

The median expression levels of LAMB3 mRNA in tumor tissues and normal tissues were somewhat lower than the mean

Discussion

In the current study, we asked whether the expression of LAMB3 mRNA and accumulation of laminin-5β3 protein were clinically significant in ESC. In previous studies, expression of a similar protein (laminin-5γ2) in the invasive front of ESC was significantly correlated with depth of invasion, lymph node metastasis, distant metastasis, pTNM stage and recurrence.12 Therefore, laminin 5 plays an important role in the progression of esophageal cancer. Based on the immunohistochemical data in the

Conclusions

In the current study, we examined the expression of two molecules localized mainly in the basement membrane zone and associated with invasion and metastasis. Our findings suggest that the combined the expression of LAMB3 and COL7A1 mRNAs may represent a new prognostic biomarker for ESC.

Conflict of interest

We hereby declare that there is no potential or actual personal, financial or political interest related to this article.

Acknowledgment

This work was supported by the following grant sponsors: CREST, Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant numbers 17109013, 17591411, 17591413, 18390367, 18590333, 18659384 and 18790964; The Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for Scientific Research on Priority Areas, grant number 18015039; Third Term Comprehensive Ten-year Strategy for Cancer Control,

References (24)

  • N. Koshikawa et al.

    Overexpression of laminin gamma2 chain monomer in invading gastric carcinoma cells

    Cancer Res

    (1999)
  • Y. Fukai et al.

    Correlation between laminin-5 gamma2 chain and epidermal growth factor receptor expression in esophageal squamous cell carcinomas

    Oncology

    (2005)
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