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.

Prognostic Significance of Cytoplasmic SPNS2 Expression in Patients with Oral Squamous Cell Carcinoma

“…For TMAs, typical OSCC tissues and adjacent epithelial tissues were harvested, included 264 primary OSCC samples. The samples were fixed using paraffin to perforate tissue cylinders (2 mm in diameter) to construct OSCC and adjacent TMAs by a homemade, semi-automated tissue array in the Department of Pathology at Changhua Christian Hospital [ 39 ].…”

“…Immunohistochemical staining was performed as previously described [ 39 , 40 ]. After deparaffinization and hydration using ethanol at various concentrations, the TMAs were subjected to antigen retrieval using 0.01 M citrate buffer (pH 6.0) in a microwave, and incubated sequentially in 3% H 2 O 2 to inhibit endogenous peroxidase activity and then in 10% normal goat serum at 37 °C for 1 h. The TMAs were then mixed with solution containing polyclonal rabbit anti-human SPNS2 antibodies (Dilution 1:100×; Catalog number: NBP1-54345; Novus Biologicals, Littleton, CO, USA) at 4 °C overnight.…”

“…Samples were classified as positive or negative based on the following scores describing SPNS2 protein expression: 0 (No staining), 1+ (Weak positive expression), 2+ (Moderately positive expression), and 3+ (Strongly positive expression). Finally, we were further classified into two groups: (1) negative group includes 0 (No staining); 1+ (Weak positive expression); (2) positive group includes 2+ (Moderately positive expression); and 3+ (Strongly positive expression) [ 39 , 40 ].…”

Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours

“…It is unclear, however, what role ADAMTS processing may play in the activity and regulation of LOX and LOXL1 in solid cancers and more work is needed in this area. Overexpression of ADAMTS2 and 14 in gastric cancer [ 93 ] and breast carcinoma [ 94 ], respectively, was associated with poorer prognosis in patients, however, in oral squamous cell carcinoma, decreased expression of ADAMTS14 was associated with more advanced stage of disease and worse survival [ 95 ]. Although these studies did not directly examine changes to the LOX family, it is possible that dysregulation of ADAMTS2 and14 could be altering the regulation of LOX and LOXL1 and contributing to cancer progression reported and is an interesting area for further investigation.…”

Investigation of the underlying hub genes and molecular pathogenesis in gastric cancer by integrated bioinformatic analyses

“…[151] and ITGBL1 [152] were involved in development of GC. Enriched up regulated genes such as COL4A2 [153], ITGA11 [154], LAMA5 [155], COL5A2 [156], ADAMTS4 [157], ADAMTS14 [158], ANXA13 [159], HTRA3 [160] and ADAMTS12 [161] were responsible for invasion of various types of cancer cells, but these genes may be associated with invasion of GC cells. Enriched up regulated genes such as COMP (cartilage oligomeric matrix protein) [162], TNC (tenascin C) [163], ITGB8 [164], FSTL3 [165] and PLXNA1 [166] were important for proliferation of many cancer cells types, but these genes may be liable for proliferation of GC cells.…”