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. 2017 Jan 1;14(1):37-44.
doi: 10.7150/ijms.17024. eCollection 2017.

Plasma levels of the tissue inhibitor matrix metalloproteinase-3 as a potential biomarker in oral cancer progression

Chun-Wen Su  1 , Bo-Feng Su  2 , Whei-Ling Chiang  3 , Shun-Fa Yang  4 , Mu-Kuan Chen  5 , Chiao-Wen Lin  6
Affiliations

Plasma levels of the tissue inhibitor matrix metalloproteinase-3 as a potential biomarker in oral cancer progression

Chun-Wen Su et al. Int J Med Sci. .

Abstract

Oral cancer is the most common malignancy with poor prognosis and is the fourth most common cancer in men in Taiwan. The tissue inhibitor of metalloproteinase-3 (TIMP3) acts as a tumor suppressor gene by inhibiting the growth, angiogenesis, migration, and invasion of cancer cells. However, few studies have examined the association of plasma TIMP3 levels with oral squamous cell carcinoma (OSCC), and the role of plasma TIMP3 levels in OSCC progression is still unclear. We measured the plasma TIMP3 levels of 450 OSCC patients and 64 healthy controls by using a commercial enzyme-linked immunosorbent assay. We also analyzed TIMP3 mRNA levels of 328 OSCC patients and 32 normal tissues from The Cancer Genome Atlas (TCGA) dataset. Our results revealed that plasma TIMP3 levels were significantly lower in patients with OSCC than in healthy controls (p < 0.001). Moreover, plasma TIMP3 levels in patients with OSCC were significantly associated with the tumor stage and tumor status but not with the lymph node status, metastasis, and cell differentiation. To verify our findings, we also examined TCGA bioinformatics database and discovered similar results for the association with the pathological stage of OSCC. In conclusion, our results suggest that plasma TIMP3 is a potential biomarker for predicting the tumor stage and T status in patients with OSCC.

Keywords: TIMP3; biomarker.; oral squamous cell carcinoma.

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Conflict of interest statement

There are no conflicts of interest to declare.

Figures

Figure 1
Figure 1
ELISA-determined plasma TIMP3 level of OSCC patients. (A) TIMP3 levels were compared according to normal control and OSCC patients. (B) TIMP3 levels were compared according to stage. (C) TIMP3 levels were compared according to tumor T status. (D) TIMP3 levels were compared according to N status. (E) ROC curve of plasma TIMP3 in discriminating between controls and patients with OSCC. AUC: area under curve.
Figure 2
Figure 2
TIMP3 mRNA level of OSCC patients from TCGA database. (A) TIMP3 mRNA level of different type of cancer from The Broad Institute TCGA GDAC Firehose. (B) TIMP3 levels were compared according to normal people and OSCC patients. (C) TIMP3 levels were compared according to stage. (D) TIMP3 levels were compared according to tumor T status. (E) TIMP3 levels were compared according to N status. THCA: thyroid carcinoma. STES: stomach and esophageal carcinoma. PRAD: prostate adenocarcinoma. PAAD: pancreatic adenocarcinoma. LUSC: lung squamous cell carcinoma. LUAD: lung adenocarcinoma. LIHC: liver hepatocellular carcinoma. HNSC: head and neck squamous cell carcinoma. ESCA: esophageal carcinoma. CESC: cervical and endocervical cancers. BRCA: breast invasive carcinoma.
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