Brief Article
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World J Gastroenterol. May 21, 2013; 19(19): 2941-2949
Published online May 21, 2013. doi: 10.3748/wjg.v19.i19.2941
Predominant mucosal IL-8 mRNA expression in non-cagA Thais is risk for gastric cancer
Sirikan Yamada, Shunji Kato, Takeshi Matsuhisa, Luksana Makonkawkeyoon, Masaru Yoshida, Thiraphat Chakrabandhu, Nirush Lertprasertsuk, Pawit Suttharat, Bandhuphat Chakrabandhu, Shin Nishiumi, Wilaiwan Chongraksut, Takeshi Azuma
Sirikan Yamada, Thiraphat Chakrabandhu, Pawit Suttharat, Bandhuphat Chakrabandhu, Wilaiwan Chongraksut, Division of Gastrointestinal Surgery and Endoscopy, Department of Surgery, Chiang Mai University, Chiang Mai 50200, Thailand
Shunji Kato, Department of Surgery, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
Takeshi Matsuhisa, Department of Gastroenterology and Endoscopy, Tama-Nagayama Hospital, Nippon Medical School, Nagayama, Tama-shi, Tokyo 206-8512, Japan
Luksana Makonkawkeyoon, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
Masaru Yoshida, Shin Nishiumi, Takeshi Azuma, Department of Gastroenterology, International Center for Medical Research and treatment, Kobe University School of Medicine, Kobe, Hyogo 650-0017, Japan
Nirush Lertprasertsuk, Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
Author contributions: Yamada S designed the research methodology, performed the majority of endoscopic examinations, experiments, analysis, and manuscript writing; Kato S, Yoshida M, Nishiumi S and Makonkawkeyoon L provided experimental supervision, cell culture, and guidance for molecular genetic methods; Chakrabandhu T, Chakrabandhu B and Suttharat P assisted for gastric surgery; Matsuhisa T provided the serum pepsinogen level test; Lertprasertsuk N provided pathologic examination and Helicobacter pylori infection detection; Chongraksut W provided assistance for statistical analytical tools; Azuma T and Kato S were involved in editing the manuscript.
Supported by JSPS Ronpaku (Dissertation PhD) program (No. NRCT 10726) award by Japan Society for the Promotion of Scince and in collaboration with Kobe University School of Medicine, Kobe, Japan; JSPS Asian CORE Program 2012, Nippon Medical School, and the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand (in part)
Correspondence to: Sirikan Yamada, MD, Division of Gastrointestinal Surgery and Endoscopy, Department of Surgery, Chiang Mai University, 239 Huay Kaew Road, Tambon Suthep, Muang District, Chiang Mai 50200, Thailand.
Telephone: +66-81-6716737 Fax: +66-53-946139
Received: December 28, 2012
Revised: April 1, 2013
Accepted: April 9, 2013
Published online: May 21, 2013

AIM: To study gastric mucosal interleukine-8 (IL-8) mRNA expression, the cytotoxin-associated gene A (cagA) mutation, and serum pepsinogen (PG) I/II ratio related risk in Thai gastric cancer.

METHODS: There were consent 134 Thai non-cancer volunteers who underwent endoscopic narrow band imaging examination, and 86 Thais advance gastric cancer patients who underwent endoscopic mucosal biopsies and gastric surgery. Tissue samples were taken by endoscopy with 3 points biopsies. The serum PG I, II, and Helicobacter pylori (H. pylori) immunoglobulin G (IgG) antibody for H. pylori were tested by enzyme-linked immunosorbent assay technique. The histopathology description of gastric cancer and non-cancer with H. pylori detection was defined with modified Sydney Score System. Gastric mucosal tissue H. pylori DNA was extracted and genotyped for cagA mutation. Tissue IL-8 and cyclooxygenase-2 (COX-2) mRNA expression were conducted by real time relative quantitation polymerase chain reaction. From 17 Japanese advance gastric cancer and 12 benign gastric tissue samples, all were tested for genetic expression with same methods as well as Thai gastric mucosal tissue samples. The multivariate analysis was used for the risk study. Correlation and standardized t-test were done for quantitative data, P value < 0.05 was considered as a statistically significant.

RESULTS: There is a high non cagA gene of 86.8 per cent in Thai gastric cancer although there are high yields of the East Asian type in the positive cagA. The H. pylori infection prevalence in this study is reported by combined histopathology and H. pylori IgG antibody test with 77.1% and 97.4% of sensitivity and specificity, respectively. The serum PG I/II ratio in gastric cancer is significantly lower than in the non-cancer group, P = 0.045. The serum PG I/II ratio of less than 3.0 and IL-8 mRNA expression ≥ 100 or log10≥ 2 are significant cut off risk differences between Thai cancer and non-cancer, P = 0.03 and P < 0.001, respectively. There is a significantly lower PGI/II ratio in Japanese than that in Thai gastric cancer, P = 0.026. Serum PG I/II ratio at cut off less than 3.0 and IL-8 mRNA expression Raw RQ > 100 or log10 > 2 are significantly difference between Thai cancer group when compared to non-cancer group, P = 0.013 and P < 0.001, respectively. In the correlation study, low PG I/II ratio does not associate with chronic atrophic gastritis severity score in Thais non-cancer cases. However, there is a trend, but not significant convert correlation between IL-8 mRNA expression level and low PG I/II ratio in Thai positive H. pylori infection. The high expression of IL-8 gene demonstrates a poorer prognosis by stage and histology.

CONCLUSION: Predominant gastric mucosal IL-8 mRNA expression level, H. pylori infection, and low PG I/II ratio are relative risks for Thai gastric cancer without correlation with cagA mutation.

Keywords: Gastric cancer, CagA mutation, Interleukine-8 mRNA expression, Helicobacter pylori, Pepsinogen I/II ratio

Core tip: A high level of interleukine-8 (IL-8) mRNA expression was detected in more than eighty percent of Thai gastric cancer patients and nearly two fold in the normal Thai population. The majority of northern Thai gastric cancer patients who had negative cagA gene Helicobacter pylori infection even with or without its mutation, still have a high IL-8 mRNA expression level. The pathogenesis of Thai gastric cancer may primarily involve another gate-way besides the bacterial factor. The results show that there is a predominantly cancer inflammation state regulated by IL-8 mRNA expression level that can be detected in Thai gastric cancer patients.