口腔鱗狀上皮細胞癌是世界上常見的癌症之一，癌細胞轉移在癌症發展的過程中屬於最致命的一步，一般而言，此時腫瘤在原發部位相對地常是呈現極大尺寸，然而更令人正視的問題是腫瘤轉移可能源自於一個小尺寸的原發腫瘤，因此如何早期診斷出罹患這類高侵犯性癌症之病患成了治療上重要的一步，除了臨床醫師常用之臨床病理特徵外，可能得闡明有關癌細胞轉移的詳細機轉以得致更多之相關分子標記。在我們初步針對臨床樣本所做的研究中發現galectin-1為淋巴轉移相關的蛋白質之一，galectin-1屬於galectin家族中的原型，已經發現有多項與腫瘤生物學相關之重要的功能，包括細胞凋亡與細胞增生的調控、細胞移動相關之黏著力、血管新生和免疫的調節等等。從許多其他腫瘤研究中顯示在腫瘤侵犯前緣與其鄰近間質組織galectin-1表現與臨床上腫瘤侵襲性有明顯正相關，在本研究中使用8例正常口腔黏膜上皮、10例口腔上皮內腫瘤、64例原發口腔鱗狀上皮細胞癌及其中17例轉移至頸部淋巴之鱗狀上皮細胞癌等等，分別以免疫組織化學染色法及定量即時連鎖聚合脢反應進行其蛋白質與轉錄體分析，結果發現侵犯前緣之腫瘤細胞質中galectin-1蛋白之過度表現則在早期癌化及腫瘤轉移時期皆具有明顯正相關，而腫瘤鄰近間質組織中galectin-1蛋白之過度表現則只在早期癌化時期中有明顯正相關。但在定量即時連鎖聚合脢反應分析中卻看不到轉錄子明顯之正相關；但透過鐳射輔助顯微切割與定量即時連鎖聚合脢反應分析，分別來看腫瘤上皮與鄰近間質組織中galectin-1轉錄子表現可得致與蛋白質表現相似之結果。Kaplan-Meier存活分析及Cox’s proportional hazards model進行單一變項分析可知在早期T分期的36位病患中，若是同時表現galectin-1 蛋白及轉錄子會有明顯較差之預後情形。總而言之，我們以口腔鱗狀上皮細胞癌之臨床檢體為模型，發現在腫瘤細胞質及鄰近間質組織的galectin-1蛋白過度表現與早期癌化過程皆有顯著相關性，而在腫瘤轉移階段則以腫瘤細胞為主。本研究將有助於闡明在鄰近間質組織及位於侵犯前緣之腫瘤細胞的微環境中，galectin-1蛋白在口腔癌化過程中依不同時期和不同位置的過度表現將扮演不同之功能，這將在我們進一步探討中提供強而有力的支持證據。

Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms worldwide. Metastasis is a final and fatal step in the progression of OSCC and always accompanies with a large primary tumor. However, metastasis may occur in a small primary tumor and progresses rapidly. Therefore, early diagnosis is important for this subgroup. In addition to clinicopathological parameters, we have to study molecular mechanisms of cancer metastasis to find the applicable biomarkers. In our preliminary studies, galectin-1 has been proved to be one of significant up-regulated tumor-associated proteins via the proteomics analysis in OSCC tissues. Galectin-1, a prototype of the galectin family, has been shown to play important functions in several aspects of cancer biology, including modulation of cell apoptosis, proliferation, migration and adhesion, angiogenesis and immune modulation. Aggressive behavior correlated with the increased at the invasion front and the tumor-associated stroma has been demonstrated in many types of neoplasms. To determine the clinical significance of galectin-1, its expression at this specific microenvironment was analyzed in various stages of oral tumorigenesis. Immunohistochemical analysis of galectin-1 expression in 8 normal oral mucosa tissues (NOMTs), 10 oral intraepithelial neoplasms (OIEDs), 64 primary OSCCs and 17 metastatic carcinoma lesions was carries out and corroborated by RT-qPCR. Galectin-1 protein was significantly overexpressed at the tumor-associated stroma as well as the invasion front during early oral carcinogenesis (P<0.05). During the metastatic stage, the only one present significant immunoreactivity was the tumor invasion front (P<0.05). Although, there was no any significance galectin-1 mRNA upregulation in cancerous tissue in comparison to adjacent NOMT, the significant upregulated galectin-1 in stromal tissue during early-staged OSCC and in epithelial tissue at the metastatic stage, which were taken from the laser-assisted microdissected cancerous tissue. Kaplan-Meier survival analysis as well as univariated analysis using the Cox’s proportional hazards model showed that co-expression of galectin-1 protein and mRNA correlated with worse disease-specific survival in early T-staged OSCC (P=0.024 and P=0.047, respectively). Overall, the results suggest that galectin-1 upregulation at the invasion front and tumor-associated stroma plays important roles in oral carcinogenesis at two important stages: early carcinogenesis and regional lymph node metastasis. The pathogenetic roles of galectin-1 in oral tumorigenesis deserve further investigation.

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