Evidence-Based Medicine
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World J Gastroenterol. Sep 14, 2014; 20(34): 12202-12211
Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12202
Cell-type specificity of β-actin expression and its clinicopathological correlation in gastric adenocarcinoma
Shafqat A Khan, Monica Tyagi, Ajit K Sharma, Savio G Barreto, Bhawna Sirohi, Mukta Ramadwar, Shailesh V Shrikhande, Sanjay Gupta
Shafqat A Khan, Monica Tyagi, Ajit K Sharma, Sanjay Gupta, Epigenetics and Chromatin Biology Group, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, MH 410210, India
Savio G Barreto, Shailesh V Shrikhande, Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, MH 400012, India
Bhawna Sirohi, Medical Oncology-GI and Breast Unit, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, MH 400012, India
Mukta Ramadwar, Department of Pathology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, MH 400012, India
Savio G Barreto, Medanta Institute of Hepatobiliary and Digestive Sciences, Medanta, The Medicity, Gurgaon, Haryana 122001, India
Author contributions: Gupta S and Khan SA conceived and designed the experiments; Khan SA, Tyagi M and Sharma AK performed the experiments; Barreto SG, Sirohi B and Shrikhande SV provided tissue samples and related clinical data; Khan SA, Ramadwar M and Gupta S analyzed the data; Khan SA, Barreto SG and Gupta S contributed in figure and analysis tools; Khan SA, Barreto SG and Gupta S wrote the paper.
Supported by TMH-IRG for project funding (account number-466), Advanced Center for Treatment Research and Education in Cancer, India for funding to Gupta lab
Correspondence to: Sanjay Gupta, PhD, Principal Investigator, Scientific Officer “F”, Epigenetics and Chromatin Biology Group, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, MH 410210, India. sgupta@actrec.gov.in
Telephone: +91-22-27405086 Fax: +91-22-27405085
Received: December 14, 2013
Revised: March 13, 2014
Accepted: May 23, 2014
Published online: September 14, 2014
Processing time: 278 Days and 17 Hours
Abstract

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.

Keywords: Gastric cancer; β-actin; Immunohistochemistry; Epithelial cells; Inflammatory cells; Tumor infiltrating immune cells; Adjacent mucosa; Resection margin

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.