Increased expression of metadherin protein predicts worse disease‐free and overall survival in laryngeal squamous cell carcinoma

Abstract

Metadherin (MTDH) is involved in tumourigenesis and cancer progression in multiple human malignancies. However, the MTDH protein has rarely been reported in laryngeal squamous cell carcinoma (LSCC). The expression pattern of the MTDH protein in 176 primary archival LSCC and 27 corresponding adjacent noncarcinoma specimens was detected by immunohistochemistry and further correlated with clinicopathological parameters. The results demonstrated that 161 (91.48%) primary LSCC samples stained positive for MTDH; however, staining was barely detectable in all adjacent noncarcinoma samples. Moreover, the expression of the MTDH protein was significantly associated with the primary tumour site (p 5 0.021), T classification (p 5 0.002), clinical stage (I 1 II/III 1 IV; p < 0.001), lymph node metastasis (p < 0.001) and postoperational recurrence (p < 0.001). Kaplan-Meier analysis revealed that MTDH expression was significantly associated with worse disease-free survival (DFS) and overall survival (OS) rates in patients with LSCC (both p < 0.001). When lymph node metastasis and MTDH expression were considered together, patients with lymph node metastasis and high MTDH expression had both poorer DFS and OS rates than others (both p < 0.001). Finally, multivariate analysis demonstrated that MTDH expression was an independent prognostic factor for both DFS and OS rates in patients with LSCC. Strong MTDH expression was negatively correlated with a canonical epithelial-mesenchymal transition molecule E-cadherin (p < 0.001) and positively associated with proangiogenic protein vascular endothelial growth factor (p < 0.001). MTDH overexpression was tightly associated with more aggressive tumour behaviour and a poor prognosis, indicating that MTDH is a valuable molecular biomarker for LSCC progression.

Metadherin in prostate, bladder, and kidney cancer: A systematic review

“…A study revealed that MTDH promotes invasion and metastasis through the activation of nuclear factor-κB (NF-κB), interleukin-8 and matrix metalloproteinase-9 in breast cancer (12), which is consistent with studies in non-small cell lung cancer and glioma (13,14). MTDH has been shown to be associated with a poor prognosis in malignancies, including non-small cell lung cancer, invasive breast cancer, laryngeal squamous cell carcinoma, gallbladder adenocarcinoma, tongue carcinoma and bladder cancer (15)(16)(17)(18)(19). MTDH is also associated with the prognosis of carcinoma, possibly due to chemoresistance and radiosensitivity in cancer therapy (20,21).…”

“…MTDH has been cloned for nearly ten years (4-6) and is considered to be an important oncogene in carcinogenesis, tumor progression and metastasis, via a series of signaling pathways (7-9). However, as the exact functions of MTDH in cancer remain unclear, particularly in malignant tumors, future investigations are required (10).Recent studies have shown that high expressions of MTDH are present in various tumors, involving the nervous, urogenital, respiratory and digestive systems (9,(11)(12)(13)(14)(15)(16)(17)(18)(19). Evidence indicates that MTDH knockdown significantly inhibited the growth of gastric cancer cells (9).…”

Metadherin is required for the proliferation, migration, and invasion of esophageal squamous cell carcinoma and its meta-analysis

“…Additionally, multiple studies have suggested that MTDH was associated with tumor invasion and migration. [19][20][21][22][23] We confirmed that MTDH inhibited ESCC cell migration and invasion in vitro, indicating that upregulation of MTDH was significantly associated with metastasis and poorer prognosis of patients with ESCC, which was further verified with meta-analysis carried out on the studies regarding MTDH in SCC. [19][20][21][22][23][24][25][26][27][28] In our meta-analysis, we found that there were significant relationships between MTDH expression in SCC and NAT; SCC tissues with and without lymph node metastasis; clinical stage I and II vs clinical stage III and IV; and T1-T2 vs T3-T4 tissues, [19][20][21][22][23][24][25][26][27][28] which may imply the possibility of using the MTDH expression level as a clinical biomarker of SCC.…”

“…Consequently, we had meta-analyzed the expression of MTDH in SCC through retrieving the relevant literature. Eventually, the 10 eligible studies 6,11,[19][20][21][22][23][24][25][26] were identified and selected (Table III). MTDH positivity and overexpression were significantly different between SCC and its paired normal 0.53]) (Fig 6, C and D).…”

Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis

“…Finally, it should be noted that the metastasis-promoting function of MTDH is likely to exist in other cancer types, beyond breast and prostate cancers. Several recent studies indeed showed abnormal MTDH expression was associated with lymph node metastasis and a worse prognosis in additional cancer types including laryngeal squamous cell carcinoma (31), squamous cell carcinoma of the head and neck (32), and hepatocellular carcinoma (33), and overexpression of MTDH increases experimental metastasis of hepatocellular carcinoma cells (34). …”