Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12202
Revised: March 13, 2014
Accepted: May 23, 2014
Published online: September 14, 2014
Processing time: 278 Days and 17 Hours
AIM: To investigate cell type specific distribution of β-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters.
METHODS: β-actin is a housekeeping gene, frequently used as loading control, but, differentially expresses in cancer. In gastric cancer, an overall increased expression of β-actin has been reported using tissue disruptive techniques. At present, no histological data is available to indicate its cell type-specific expression and distribution pattern. In the present study, we analyzed β-actin expression and distribution in paired normal and tumor tissue samples of gastric adenocarcinoma patients using immunohistochemistry (IHC), a tissue non-disruptive technique as well as tissue disruptive techniques like reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Correlation of β-actin level with clinicopathological parameters was done using univariate analysis.
RESULTS: The results of this study showed significant overexpression, at both mRNA and protein level in tumor tissues as confirmed by RT-PCR (1.47 ± 0.13 vs 2.36 ± 0.16; P < 0.001) and western blotting (1.92 ± 0.26 vs 2.88 ± 0.32; P < 0.01). IHC revealed that β-actin expression is majorly distributed between epithelial and inflammatory cells of the tissues. Inflammatory cells showed a significantly higher expression compared to epithelial cells in normal (2.46 ± 0.13 vs 5.92 ± 0.23, P < 0.001), as well as, in tumor tissues (2.79 ± 0.24 vs 6.71 ± 0.14, P < 0.001). Further, comparison of immunostaining between normal and tumor tissues revealed that both epithelial and inflammatory cells overexpress β-actin in tumor tissues, however, significant difference was observed only in inflammatory cells (5.92 ± 0.23 vs 6.71 ± 0.14, P < 0.01). Moreover, combined expression in epithelial and inflammatory cells also showed significant increase (4.19 ± 0.15 vs 4.75 ± 0.14, P < 0.05) in tumor tissues. In addition, univariate analysis showed a positive correlation of β-actin level of inflammatory cells with tumor grade (P < 0.05) while epithelial cells exhibited negative correlation (P > 0.05).
CONCLUSION: In gastric cancer, β-actin showed an overall higher expression predominantly contributed by inflammatory or tumor infiltrating immune cells of the tissue microenvironment and correlates with tumor grade.
Core tip: Clinical implications of β-actin have been ignored despite the reports of its differential expression in cancer. The present study provides first histological evidence of an overall increase in β-actin expression in gastric cancer compared to histologically normal adjacent mucosa. Inflammatory and epithelial cells of tumor tissues showed differential pattern of β-actin expression and correlated with tumor grade. Further, overexpression of β-actin was predominantly contributed by inflammatory cells, suggesting further extensive studies to use β-actin as a diagnostic and prognostic biomarker and target of direct or indirect chemotherapeutic intervention.