Decreased Muc5AC expression is associated with poor prognosis in gastric cancer

• Published in: International journal of cancer 2014-01, Vol.134 (1), p.114-124
• Main Authors: Kim, Sung Mi, Kwon, Chae Hwa, Shin, Nari, Park, Do Youn, Moon, Hyun Jung, Kim, Gwang Ha, Jeon, Tae Yong
• Format: Article
• Language: English
• Subjects: adenocarcinoma; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Biological and medical sciences; Biomarkers; Biomarkers, Tumor - analysis; Blotting, Western; Cancer; Cell adhesion & migration; Cell Movement - physiology; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Female; Gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Gene Knockdown Techniques; Humans; Immunohistochemistry; Infections; Kinases; Male; Medical research; Medical sciences; Middle Aged; Muc5AC; Mucin 5AC - biosynthesis; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Invasiveness - pathology; Oligonucleotide Array Sequence Analysis; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; stomach; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transcriptome; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.28345

Mucins reportedly play numerous key roles in carcinogenesis, including in tumor invasion, regulation of differentiation and tumor cell proliferation. We investigated the effect of Muc5AC, a secreted mucin, on the invasiveness/migratory capability of gastric cancer cells and the prognostic significance of Muc5AC in gastric cancer patients. The clinicopathological and prognostic significance of Muc5AC expression was validated using immunohistochemical analysis in 412 gastric cancer patients. Differential gene expression was investigated using complementary DNA microarray analysis of 48 fresh tumor tissue samples. Silencing of Muc5AC by using a small hairpin RNA‐containing lentivirus increased the invasion and migration of SNU216 and AGS cells as well as Akt phosphorylation and the expression of vascular endothelial growth factor and matrix metalloproteinase‐7, which were blocked by inhibitors of the phosphatidylinositol 3‐kinase/Akt pathway. Loss of Muc5AC expression was significantly associated with tumor progression (advanced T stage; p = 0.004), lymph node metastases (p = 0.001), lymphovascular invasion (p < 0.0001), and increased tumor size (p = 0.027). Lower MUC5AC expression was identified as an independent poor prognostic factor in diffuse‐type gastric cancer by using the Cox regression proportional hazard model (hazard ratio, 2.39; p = 0.043). Complementary DNA microarray analysis revealed 86 differentially expressed genes, including genes related to metastasis and invasion, in gastric cancer tissues with high (≥25%) and low (