title: Overexpression of HOXA10 promotes gastric cancer cells proliferation and HOXA10(+)/CD44(+) is potential prognostic biomarker for gastric cancer.
abstract: Gastric cancer (GC) is a malignant cancer with poor prognosis. This study aims to investigate the roles of homeobox A10 (HOXA10) in GC and the correlations between HOXA10/CD44 expression and GC prognosis. Based on qRT-PCR and Western Blot analyses in 50 pairs of fresh GC samples and adjacent normal samples, it is identified that HOXA10 was significantly up-regulated in GC tissues at mRNA and protein levels. Cell proliferation, migration, and invasion were enhanced in GC cells with overexpressed HOXA10, while inhibited in cells with silenced HOXA10. Through IPA software, HOXA10 was predicted to interact with CD44 via MSN, which was preliminarily confirmed by using Western Blot. Through immunohistochemistry and tissue microarray (N=264), it is found that HOXA10 expression was significantly correlated with tumor size (P=0.011) and CD44 expression (P<0.001), while CD44 expression was significantly correlated with tumor size (P<0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.001), UICC stage (P<0.001), histological differentiation (P<0.001), and HOXA10 expression (P<0.001). Additionally, the over-all survival and disease-free survival of HOXA10(+)/CD44(+) patients were dramatically decreased in comparison with that of HOXA10(+)/CD44(-), HOXA10(-)/CD44(+), or HOXA10(-)/CD44(-) patients (P<0.001), suggesting that the combinatory expression of HOXA10 and CD44 was correlated with poor GC prognosis. In conclusion, HOXA10 and CD44 might play roles in GC tumorigenesis, metastasis, and invasion. HOXA10(+)/CD44(+) expression might serve as a prognostic biomarker for GC, which needs more studies to validate.
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Pathology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China.
authors.forename: Su
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China.
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Wen
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China.
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China.
authors.forename: Xing-Wu
authors.initials: XW
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Qiu
authors.affiliation: Department of Pathology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China.
authors.forename: Hua-Mei
authors.initials: HM
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China.
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Peng
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20080, China. Electronic address: cz-zhou@163.com.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; C069634:HOXA10 protein, human
keywords: Biomarker; CD44; Gastric cancer; HOXA10; Prognosis