Correlations of MUC15 overexpression with clinicopathological features and prognosis of glioma

Abstract

The abnormal expression of MUC15, a novel cell membrane-associated mucin, has been reported to predict poor survival in several cancers. The aim of the present study was to examine the expression of MUC15 in glioma and its correlation with clinicopathological features, including the survival of patients with glioma. The mRNA expression level of MUC15 was determined by RT-PCR, quantitative RT-PCR (RT-qPCR) and Western blotting in seven normal brain tissues and seven glioma tissues, respectively. The protein expression level of MUC15 was immunohistochemically detected in paraffin-embedded samples of 317 glioma tissues and 115 noncancerous brain tissues. The association of MUC15 expression levels with the clinicopathologic features and the prognosis was analyzed. The results showed that both mRNA and protein levels of MUC15 were significantly increased in glioma as compared with those in noncancerous brain tissue. Moreover, MUC15 overexpression was positively correlated with the advanced clinical stages of glioam patients (P<0.01). Furthermore, MUC15 expression levels were significantly correlated with the progression of glioma (P<0.001). Survival analysis indicated that glioma patients with higher MUC15 expression had a significantly shorter overall and 5-year survival time than those with low MUC15 expression. Multivariate analysis suggested that MUC15 overexpression was an independent factor for prognosis (hazard risk: 3.216; P=0.009). It was concluded that MUC15 is overexpressed in glioma tissues. Its overexpression correlates with tumor progression and it is a potentially unfavorable prognostic factor for patients with glioma.

Keywords

MUC15 / mucins / glioma / prognosis

References

[1] OmuroA, DeAngelisLM. Glioblastoma and other malignant gliomas: a clinical review. JAMA, 2013, 310(17): 1842-1850

[2] WenPY, KesariS. Malignant gliomas in adults. N Engl J Med, 2008, 359(5): 492-507

[3] GururanganS, FangusaroJ, PoussaintTY, et al.. Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas—a Pediatric Brain Tumor Consortium study. Neuro Oncol, 2014, 16(2): 310-317

[4] NygaardR, KivivuoriSM. Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and systemic metronomic combination therapy. Anticancer Drugs, 2012, 23(3): 342-346

[5] YuX, ZhangWD, NingQ, et al.. MicroRNA-34a inhibits human brain glioma cell growth by down-regulation of notch1. J Huazhong Univ Sci Technol [Med Sci], 2012, 32(3): 370-374

[6] MukasaA, TakayanagiS, SaitoK, et al.. Significance of IDH mutations varies with tumor histology, grade, and genetics in Japanese glioma patients. Cancer Sci, 2012, 103(3): 587-592

[7] GuoD, ReinitzF, YoussefM, et al.. An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. Cancer Discov, 2011, 1(5): 442-456

[8] AldertonGK. Tumorigenesis: the origins of glioma. Nat Rev Cancer, 2011, 11(9): 627

[9] ShyuMK, LinMC, ShihJC, et al.. Mucin 15 is expressed in human placenta and suppresses invasion of trophoblast-like cells in vitro. Hum Reprod, 2007, 22(10): 2723-2732

[10] ByrdJC, BresalierRS. Mucins and mucin binding proteins in colorectal cancer. Cancer metastasis Rev, 2004, 23(1–2): 77-99

[11] NamKH, NohTW, ChungSH, et al.. Expression of the membrane mucins MUC4 and MUC15, potential markers of malignancy and prognosis, in papillary thyroid carcinoma. Thyroid, 2011, 21(7): 745-750

[12] RikerAI, EnkemannSA, FodstadO, et al.. The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Medical Genomics, 2008, 1: 13

[13] KerschnerJE. Mucin gene expression in human middle ear epithelium. Laryngoscope, 2007, 117(9): 1666-1676

[14] HoorensPR, RinaldiM, LiRW, et al.. Genome wide analysis of the bovine mucin genes and their gastrointestinal transcription profile. BMC Genomics, 2011, 12: 140

[15] PonnusamyMP, SeshacharyuluP, LakshmananI, et al.. Emerging role of mucins for epithelial to mesenchymal transition. Curr Cancer Drug Targets, 2013, 13(9): 945-56

[16] AnandkumarA, DevarajH. Tumour immunomodulation: mucins in resistance to initiation and maturation of immune response against tumours. Scand J Immunol, 2013, 78(1): 1-7

[17] TsuboiS. Tumor defense systems using O-glycans. Biol Pharm Bull, 2012, 35(10): 1633-1636

[18] HuangJ, CheMI, HuangYT, et al.. Overexpression of MUC15 activates extracellular signal-regulated kinase 1/2 and promotes the oncogenic potential of human colon cancer cells. Carcinogenesis, 2009, 30(8): 1452-1458

[19] SchuhmacherC, NovotnyA, FeithM, et al.. The new TNM classification of tumors of the esophagogastric junction. Surgical consequences. Chirurg (German), 2012, 83(1): 23-30

[20] WangRY, ChenL, ChenHY, et al.. MUC15 inhibits dimerization of EGFR and PI3K-AKT signaling and is associated with aggressive hepatocellular carcinomas in patients. Gastroenterology, 2013, 145(6): 1436-1448

[21] ValastyanS, WeinbergRA. Tumor metastasis: molecular insights and evolving paradigms. Cell, 2011, 147(2): 275-292