|摘要: ||背景：口腔癌為全球第六大常見惡性腫瘤，在台灣更是男性的第四大癌症，但目前缺乏有效的診斷及治療之生物標誌。舌癌在台灣是口腔癌中主要的形式之一且代表了28.10%的口腔癌。舌癌已知為極具侵犯性的腫瘤，伴隨轉移、較差的局部區域性控制及高度復發率傾向。腫瘤表面蛋白可以做為理想的癌症診斷標誌及治療標靶，其中表面蛋白受體表達增強蛋白6 (Receptor expression-enhancing protein 6, REEP6) 在許多癌症上都有高度表達的現象，但在口腔癌上的相關性卻未報導過。我們透過癌症基因體圖譜 (The Cancer Genome Atlas, TCGA) 分析發現REEP6 mRNA高表現與口腔癌的不良預後相關，但是，REEP6蛋白質表現與口腔癌病人病理特徵和存活相關性並不清楚，尤其是舌癌是口腔癌的第一大癌。因此，本研究的目的是觀察REEP6蛋白質表現對舌部鱗狀細胞癌患者的腫瘤發展和預後的影響。材料與方法：利用免疫組織化學染色法 (Immunohistochemistry, IHC) 檢測舌癌組織微陣列 (Tissue microarray,TMA) 切片中REEP6蛋白質表現量後，進行統計分析。組織微陣列中共有250個病患經由手術切除的舌部鱗狀細胞癌組織核芯 (每個病患有兩個核芯)，201個病患腫瘤鄰近的正常組織核芯 (每個病患有1個核芯) 與另外35個呼吸中止病患的正常懸雍垂組織核芯 (每個病患有1個核芯)。結果：免疫組織化學染色結果發現腫瘤組織和腫瘤鄰近正常組織的REEP6蛋白質表現量顯著高於懸雍垂正常組織 (p =0.05)，然而，REEP6蛋白質表現量與臨床病理特徵及病人存活無顯著相關。但經分層分析發現，在腫瘤較小 (T1/T2) 的病患中，高表達的REEP6蛋白質在「疾病特定存活」 (Disease-specific survival, DSS) 的風險顯著較高(調整風險比,，AHR=1.90，p=0.012) ；而年齡≦50歲 (AHR=1.87，p=0.038) 或腫瘤較小 (T1/T2) (AHR=1.64，p=0.043) 的病患中，高表達的REEP6蛋白質在「無疾病復發存活」 (Disease-free survival，DFS) 的風險也是顯著較高。結論：舌部鱗狀細胞癌患者REEP6蛋白質的表達與腫瘤癌化可能有相關性，而在特定的病患中REEP6蛋白質表達量與疾病特定存活(Disease-specific survival, DSS) 及無疾病復發存活 (Disease-free survival，DFS) 呈現負相關性。|
Backgrounds: Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers and ranks 6th most common malignancy worldwide. In Taiwan, oral cancer was the 4th most common cancer in males. Oral tongue squamous cell carcinoma (OTSCC) is the top 2 common form of oral cancer and represents 28.10% of oral cancer. OTSCC is known as an aggressive tumor with a propensity to metastasis, poorer locoregional control and a high recurrence rate. To date, there is no biomarker for diagnosis and treatment for OTSCC. Tumor surface protein is an ideal diagnostic biomarker and target for immunotherapy. The Receptor expression-enhancing protein 6 (REEP6) is a surfaced protein and highly expressed in many cancers. However, the expression level of REEP6 in OSCC has never been reported. We found that high REEP6 mRNA expression level is associated with poor prognosis in oral cancer through big data analysis with The Cancer Genome Atlas (TCGA) database analysis. Nevertheless, the association of REEP6 protein level with clinicopathological parameters and survival remains unknown. Therefore, the aim of this study was to investigate the effect of REEP6 protein expressjion on tumor progression and prognosis in patients with OTSCC.Materials and Methods: The expression of REEP6 protein in tissue microarray (TMA) was dstermined by immunohistochemistry staining (IHC) . In the tissue microarray, there were 250 surgically resected tongue squamous cell carcinoma core ( two cores in each patient) , 201 tumor adjacent normal tissue cores (one core per patient ) with another 35 ventilated patients with normal uvula tissue cores (1 core per patient) .Results: The results of immunohistochemical staining showed that the expression of REEP6 protein in tumor tissue and tumor adjacent tissues was significantly higher than that in uvula normal tissue (p = 0.05) . However, the expression of REEP6 was not significantly association with clinicopathological parameters and survival. Further, stratification analysis showed that high expression level of REEP6 in patients with small tumor (T1 / T2) had significantly poor disease-specific survival (DSS) (AHR = 1.90, p = 0.012). In patients with age ≦ 50 years (AHR = 1.87, p = 0.038) or tumors with small (T1 / T2) (AHR = 1.64, p = 0.043), high-expression level of REEP6 also had significantly worse disease-free survival (DFS).Conclusion: The expression of REEP6 in OTSCC may be associated with tumorigenesis, and the high protein level of REEP6 was not associated with shorter disease-specific survival (DSS) and disease-free recurrence (Disease-free survival, DFS) except in those patients with tumor size and age <50 years.