The Prognostic Significance of hTERT, Sp1, p53, and PKCα in Human Gastric Carcinoma: A Clinicopathological Correlation

人類胃癌組織中hTERT，Sp1，p53 與PKCα之預後意義：臨床病理學之相關性研究

雖然目前已有一些胃癌預後指標，然而同屬於某一病理階段的不同病人，其術後情形亦可能不同，因此，必須尋找其他可作為胃癌預後指標之分子以提高準確預測疾病復發率與治癒率之機率。本研究之目的即為探討hTERT，Sp1，p53 與蛋白激酶Cα(PKCα)與胃癌之臨床病理因子間之相關性，並評估做為胃癌預後指標之可行性。利用即時定量聚合酶鏈鎖反應，我們分析了42 對胃腫瘤與非腫瘤組織中hTERT，Sp1，p53 與PKCαmRNA 之表現。同一病人腫瘤與非腫瘤組織中mRNA 表現之差異使用成對t-檢定進行分析。mRNA 表現與臨床病理因子間相關性則使用雙尾卡方檢定進行分析。存活曲線則使用Kaplan-Meier 統計法獲得，並以對數等級檢定法分析mRNA 表現與存活之關係。胃癌組織中hTERT，Sp1 與PKCα mRNA 增加(p < 0.05)而p53 mRNA表現則減少(p < 0.01)。hTERT mRNA 表現與Lauren 分類及分化程度有顯著相關(p < 0.01)，而PKCα mRNA表現則與轉移有顯著相關(p < 0.01)。胃癌組織中Sp1 與PKCα mRNA 表現較多之病人明顯預後較差(p <0.05)。研究結果顯示hTERT，Sp1，p53 與PKCα mRNA 之表現與胃癌有臨床病理學的相關性，且Sp1 與PKCαmRNA 之表現可做為胃癌之預後指標。

The variability of prognosis drives an extensive search for novel prognostic markers for gastric carcinoma. The aims of this study were to clarify the correlations of hTERT, Sp1, p53, and protein kinase Cα (PKCα) with clinicopathological parameters, and to evaluate the prognostic values of these molecules for gastric carcinoma. We investigated 42 tumour/non-tumour pairs of gastric tissues. hTERT, Sp1, p53, and PKCα mRNA levels were analyzed with quantitative real-time polymerase chain reaction. Proteins were analyzed by immunohistochemistry. A paired t test was used to analyze the differences in mRNA expression levels of these molecules between tumour and non-tumour tissues in the same patient. A two-tailed χ2 test was performed to determine the significance of the differences between hTERT, Sp1, p53, and PKCα mRNA levels and clinicopathological parameters, and between hTERT mRNA and Sp1, p53, and PKCα mRNA levels. A survival curve was obtained using the Kaplan-Meier method. A log-rank test was used to assess the statistical differences in survival. hTERT, Sp1, and PKCα were upregulated (p < 0.05) and p53 was downregulated (p < 0.01) in gastric carcinoma. hTERT mRNA expression was associated with Lauren classification and degree of differentiation (p < 0.01). PKCα mRNA expression was associated with metastasis (p < 0.01). Patients with more Sp1 or PKCα mRNA had shorter survival (p < 0.05). Our results suggest that expressions of hTERT, Sp1, p53, and PKCα have clinicopathological correlations with gastric carcinoma and those of Sp1 and PKCα may be used as prognostic markers for gastric carcinoma.