Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype.
OBJECTIVE
To identify molecular biologic differences between two gastric adenocarcinoma subgroups presenting different prognoses through the analysis of microRNA and protein expression.


METHODS
Array technologies were used to generate 1146 microRNAs and 124 proteins expression profiles of samples from 60 patients with gastric cancer. For the integrative analysis, we used established mRNA expression data published in our previous study. Whole mRNA expression levels were acquired from microarray data for 60 identical gastric cancer patients. Two gastric adenocarcinoma subgroups with distinct mRNA expression profiles presented distinctly different prognoses. MicroRNA and protein expression patterns were compared between gastric cancer tissue and normal gastric tissue and between two different prognostic groups. Aberrantly expressed microRNA, associated mRNA, and protein in patients with poor-prognosis gastric cancer were validated by quantitative reverse transcription polymerase chain reaction and immunochemistry in independent patients.


RESULTS
We obtained the expression data of 1146 microRNAs and 124 cancer-related proteins. Four microRNAs were aberrantly expressed in the two prognostic groups and in cancer vs non-cancer tissues (P < 0.05). In the poor-prognosis group, miR-196b, miR-135b, and miR-93 were up-regulated and miR-29c* was down-regulated. miR-196b expression positively correlated with Homeobox A10 (HOXA10) expression (r = 0.726, P < 0.001), which was significantly increased in poor-prognosis patients (P < 0.001). Comparing gastric cancer with non-cancer tissues, 46/124 proteins showed differential expression (P < 0.05); COX2 (P < 0.001) and cyclin B1 (P = 0.017) were clearly over-expressed in the poor-prognosis group.


CONCLUSIONS
Co-activation of miR-196b and HOXA10 characterized a poor-prognosis subgroup of patients with gastric cancer. Elucidation of the biologic function of miR-196b and HOXA10 is warranted.
Jae Yun Lim, So-Young Seol, Jae Yong Cho, Department of Medical Oncology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul 135-720, South Korea.
Jae Yun
JY
Lim
Sun Och
SO
Yoon
So-Young
SY
Seol
Soon Won
SW
Hong
Jong Won
JW
Kim
Seung Ho
SH
Choi
Ju-Seog
JS
Lee
Jae Yong
JY
Cho
D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D016009:Chi-Square Distribution; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D046888:Tissue Array Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C069634:HOXA10 protein, human
Gastric cancer; Gene expression; Homeobox A10; MicroRNA; Microarray; miR-196b