驗證插入素基因群作為口腔鱗狀細胞癌腫瘤標記

背景：口腔鱗狀細胞癌的早期診斷可以提高存活率並達到更好的預後。因此，口腔鱗狀細胞癌生物標誌(biomarkers)的找尋與驗證仍是現今研究的主流之一。材料與方法：本研究取配對的口腔鱗狀細胞癌組織和自體非腫瘤組織(n = 55)，以先前研究的全基因體寡核苷酸晶片結果，篩選出插入素基因群做為候選基因，並進行定量同步化real-time RT-PCR加以驗證和定量分析。並配合臨床致病因子進行統計分析。結果：從表現上升基因群中挑選的四個基因Integrin alpha 3(ITGA3)，Integrin alpha 5(ITGA5)、Integrin beta 1(ITGB1)和Integrin beta 6(ITGB6)，經驗證和定量分析後，符合晶片所得的結果。Receiver Operator Characteristic curve (ROC curve)分析的曲線下面積對於ITGA3、 ITGA5、 ITGB1和ITGB6分別為：0.715 (95%信賴區間[CI]，0.626~0.823，p =0.004)，0.698 (95% CI，0.597~0.800，p = 0.004)，0.640 (95% CI，0.536~0.734，p= 0.011)和0.657 (95% CI，0.554~0.760，p = 0.005)，這些數據顯示，四個基因皆為具潛力的口腔鱗狀細胞癌，利用ITGA3與 ITGA5基因表現檢測口腔鱗狀細胞癌具有顯著效果。另經統計交叉分析發現，鱗狀上皮細胞癌組織與自體非腫瘤組織之基因相對表現倍數在各AJCC口腔惡性腫瘤分期之間、性別、致癌不良習癖(菸、酒與檳榔)接觸史之間無顯著差異存在，若以ITGA3、 ITGA5、 ITGB1和ITGB6做為口腔鱗狀細胞癌的生物標誌時，將不會受到上述臨床變因的影響而有所受限。但在不同病灶發生部位，ITGA3則是具有統計上差異(p = 0.005)。結論：ITGA3、 ITGA5、是具有潛力的口腔鱗狀細胞癌生物標誌。

關鍵字

插入素；生物標誌；台灣；口腔鱗狀細胞癌

並列摘要

Background: Early detection of oral squamous cell carcinoma (OSCC) is helpful for better prognosis and survival rate . The identification and validation of OSCC biomarkers are still main stream of modern researches. Materials and methods: 55 Paired-OSCC/safe margin normal tissue samples were collected. Based on our previous microarray data, 4 integins candidates were selected. Subsequently, the real-time RT-PCR is applied to validate these candidates for the suitability of OSCC detection. All results were statistically analyzed with clinicopathological factors. Results: Integrin alpha 3(ITGA3)，Integrin alpha 5(ITGA5)、Integrin beta 1(ITGB1)和Integrin beta 6(ITGB6) were selected from up-regulated genes. The area under the Receiver Operator Characteristic curve (ROC curve) for ITGA3, ITGA5, ITGB1 and ITGB6 were 0.715 (95% confidence interval [CI] = 0.626~0.823, p = 0.004), 0.698 (95% CI = 0.597~0.800, p = 0.004), 0.640 (95% CI = 0.536~0.734, p = 0.011), and 0.657 (95% CI = 0.554~0.760, p = 0.005) for OSCC patients versus normal controls respectively. These results suggested that the ITGA3, and ITGA5 were significantly detected the OSCC under the control choice of normal tissue samples. No significant difference was found between each stage of AJCC oral cancer classification, gender, and between different years of contacting history of carcinogenic factors (alcohol, betel quid and cigarette) in relative gene expression of OSCC and their paired tissues. If we use ITGA3, ITGA5, ITGB1, and ITGB6 for detecting OSCC may be less limited to these clinicopathological features of OSCC. However, there was significant difference between different tumor location in ITGA3. Conclusion: ITGA3, ITGA5 are potential biomarkers for detection of OSCC.