Dataset Information

Decreased Cytoplasmic Expression of ADAMTS14 Is Correlated with Reduced Survival Rates in Oral Squamous Cell Carcinoma Patients.

ABSTRACT: A disintegrin and metalloproteinase with thrombospondin motif 14 (ADAMTS14) is a member of the zinc-dependent protease family that is implicated in the occurrence and progression of tumors. Oral cancer (OC) is a common cancer worldwide, but it is particularly prevalent in Taiwan. However, whether the expression of ADAMTS14 is correlated with the carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has not yet been investigated. In this study, we used immunohistochemistry (IHC) to examine 250 OSCC specimens in order to identify correlations between the cytoplasmic expression of ADAMTS14 and (1) clinicopathological features of OSCC as well as (2) clinical outcomes of OSCC. Our results indicate that cytoplasmic expression of ADAMTS14 was lower in OSCC tissues than in normal tissues. In analyzing correlations between ADAMTS14 expression and clinicopathological features, we found that negative cytoplasmic expression of ADAMTS14 was significantly associated with higher frequencies of lymph node metastasis and more advanced AJCC stages (III/IV). Kaplan-Meier survival analysis revealed that negative cytoplasmic expression of ADAMTS14 was also associated with significantly worse OSCC survival. Univariate and multivariate analyses confirmed that cytoplasmic expression of ADAMTS14 was associated with lymph node metastasis, tumor stage, and tumor grade and also indicated that cytoplasmic ADAMTS14 expression may be an independent prognostic factor for OSCC. This is the first study to report that the cytoplasmic expression level of ADAMTS14 is associated with OSCC prognosis and tumor progression. Our data indicate that ADAMTS14 can serve as a prognostic marker and a potential therapeutic target for OSCC.

SUBMITTER: Lin YM

PROVIDER: S-EPMC7168220 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Decreased Cytoplasmic Expression of ADAMTS14 Is Correlated with Reduced Survival Rates in Oral Squamous Cell Carcinoma Patients.

Lin Yueh-Min YM Lin Chiao-Wen CW Lu Jeng-Wei JW Yeh Kun-Tu KT Lin Shu-Hui SH Yang Shun-Fa SF

Diagnostics (Basel, Switzerland) 20200223 2

A disintegrin and metalloproteinase with thrombospondin motif 14 (ADAMTS14) is a member of the zinc-dependent protease family that is implicated in the occurrence and progression of tumors. Oral cancer (OC) is a common cancer worldwide, but it is particularly prevalent in Taiwan. However, whether the expression of ADAMTS14 is correlated with the carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has not yet been investigated. In this study, we used immunohistochemistry (IHC) t ...[more]

PMID: 32102222

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Project description:To identify differently expressed circular RNA (circRNA) in oral squamous cell carcinoma (OSCC) and adjacent normal tissue, construct a hsa_circ_0112879-related microRNAs (miRNAs) prognostic model, and discuss the circRNA as a biomarker for early diagnosis of OSCC. The expression of hsa_circ_0112879 in OSCC cell lines and tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was plotted to estimate its clinical significance. The potential miRNA and messenger RNA (mRNA) binding to hsa_circ_009755 were predicted by R software edgeR package. Based on the median value of the risk score in the all-sample cohort, all the included patients with OSCC were divided into either high- or low-risk groups, and Kaplan-Meier analysis was performed. The ROC curve was used to verify the accuracy of the risk signature in predicting the prognosis of OSCC. By univariable Cox, least absolute shrinkage and selection operator (LASSO), and multivariable Cox analyses, we constructed a hsa_circ_0112879-related miRNAs risk model to forecast the prognosis of OSCC. The expression of hsa_circ_0112879 was significantly downregulated in the OSCC tissues and cell lines. The expression level was statistically correlated with the pathological differentiation of OSCC tumors (P=0.0285). Furthermore, 141 differentially expressed hsa_circ_0112879-related miRNAs were obtained [|log2FC| >1, false discovery rate (FDR) <0.05], of which 70 miRNAs were up-regulated in OSCC tissues, whereas 71 miRNAs were down-regulated in OSCC tissues. The area under the ROC curve (AUC) at 1-, 3-, and 5-year in the all-sample cohort was 0.591, 0.689, and 0.618, respectively. The toll-like receptor signaling pathway, Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway, and T-cell receptor (TCR) signaling pathway were mainly enriched in the high-risk group. The model and nomogram constructed herein has the ability to discriminate the prognosis of OSCC patients. Hsa_circ_0112879 may serve as a novel biomarker in the diagnosis and prognosis of OSCC.

Project description:p33(ING1b), a newly discovered candidate tumor suppressor gene and a nuclear protein, belongs to the inhibitor of growth gene family. Previous studies have shown that p33(ING1b) is involved in the restriction of cell growth and proliferation, apoptosis, tumor anchorage-independent growth, cellular senescence, maintenance of genomic stability and modulation of cell cycle checkpoints. Loss of nuclear p33(ING1b) has been observed in melanoma, seminoma, papillary thyroid carcinoma, oral squamous cell carcinoma, breast ductal cancer and acute lymphoblastic leukemia. Inactivation and/or decreased expression of p33(ING1b) have been reported in various types of cancer, including head and neck squamous cell, breast, lung, stomach, blood and brain malignancies. Since little is known about the clinicopathological significance of p33(ING1b) in esophageal squamous cell carcinoma (ESCC), this study aimed to investigate the association of p33(ING1b) expression with clinicopathological variables and particularly interesting new cysteine-histidine rich protein (PINCH) in patients with ESCC. p33(ING1b) expression was examined by immunohistochemistry in 20 normal esophageal mucosa and in 64 ESCC specimens. The results revealed that the positive expression of p33(ING1b) protein in normal squamous cells was localized in the nucleus alone and the positive rate was 95%, while in ESCCs, the positive expression was mainly in the cytoplasm, together with nuclear expression, and the positive rate was 36% (P<0.0001). Furthermore, the cases with lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P=0.001). The cytoplasmic expression of p33(ING1b) was positively related to PINCH expression (P<0.0001) in ESCC, and the cases positive for both proteins had a high lymph node metastasis rate (P=0.001). In conclusion, p33(ING1b) cellular compartmental shift from the nucleus to the cytoplasm may cause loss of normal cellular function and play a central role in the tumorigenesis and metastasis of ESCC.

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Dataset Information

Decreased Cytoplasmic Expression of ADAMTS14 Is Correlated with Reduced Survival Rates in Oral Squamous Cell Carcinoma Patients.

Publications

Decreased Cytoplasmic Expression of ADAMTS14 Is Correlated with Reduced Survival Rates in Oral Squamous Cell Carcinoma Patients.

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