Abstract
摘要:根據行政院衛生署統計,癌症為國內十大死因之首,而在全世界中,胃癌的死亡率居各種癌症死亡率的第二位,其病人五年內的存活率低於百分之十。雖然目前已經有許多的研究結果偵測出胃癌相關的標記分子,但是並沒有證據顯示這些標記分子被充分地應用於臨床診斷上。在本研究中希望藉由直接研究臨床腫瘤標本的蛋白質體來鑑定出癌症專一的蛋白質標記分子,如此就能提供癌症早期診斷早期治療的新方法,並進一步了解癌症形成的機制。
在我們初步的蛋白質體研究成果中,我們鑑定出了一些在胃癌病人的正常組織和腫瘤組織中表現差異的蛋白質,並藉由生物資訊的方法分析後,發現annexin A2和annexin A4的表現在腫瘤組織中分別比正常組織中增加了3.3倍和1.9倍。而為了確定此一蛋白質體的研究成果,我們直接針對臨床上20位病人的組織進行研究,並利用西方墨點法直接測量annexin A4的蛋白質表現量。在這些病人中,其中9位曾被幽門桿菌感染,而另外11個病人則沒有被感染過。經由研究結果可以發現,在幽門桿菌感染過的組織中,其annexin A4的表現量確實有明顯增加的趨勢。
幽門桿菌發現於1984年,並在1994年被世界衛生組織認定為第一群致癌物。許多的研究指出幽門桿菌與胃的non-Hodgkin淋巴瘤及MALToma的胃黏膜有關,當人體受到幽門桿菌的感染後會造成胃與十二指腸的病變,其包括慢性胃炎、消化性潰瘍及胃腺癌等。所以幽門桿菌與胃癌的關係就受到較廣泛的注意,甚至有些結果顯示進行幽門桿菌篩檢為陽性者較易罹患胃癌。
在初步結果中發現的annexin A2和annexin A4皆為annexin的家族成員,其中annexin A2的大量表現與腦癌、乳癌、肺癌、肝癌、胰臟癌、血癌、結腸癌及胃癌有關已是眾所皆知,並且Annexin A2也已被證實與癌細胞的增生/分化、細胞附著及發病有關。然而,annexin A4的功能及與癌症發生的關係仍所知不多。根據我們初步的研究成果及文獻搜尋的結果,我們提出了一個annexin A
Abstract: Gastric cancer is a leading cause of death worldwide, and patients have an overall 5-year survival rate of less than 10%. Several tumor markers of gastric cancer have been identified; however, no evidence has been obtained indicating that the detection of these markers precedes clinical diagnosis of gastric cancer. Proteomics studies of clinical tumor samples have led to the identification of cancer-specific proteins markers, which provides a basis for developing new methods for early diagnosis and early detection of cancers as well as clues to understanding the molecular mechanism of cancer progression.
In our preliminary results using proteomics approach, we identified many proteins with different expression between normal tissue and tumor tissue of gastric cancer patients. After bioinformatics analysis, we founded the expression of annexin A2 and annexin A4 are 3.3 and 1.9-fold more in the tumor tissue compared with the normal tissue, respectively. To confirm and investigate our proteomics results, we used twenty patients' tissues. Nine patients have been infected Helicobacter pylori (H. pylori) and eleven patients have not been infected H. pylori. We analyzed the proteins extracted from these tissues by western blotting with human-specific anti-annexin A4 antibodies and employed β-actin as an internal control to normalize the relative expression levels of the proteins. The expression of annexin A4 in tumor tissue with H. pylori infection is significantly more than without H. pylori infection.
H. pylori was discovered in 1984 and regarded as a class 1 carcinogen by the World Health Organization (WHO) in 1994. H. pylori was also found to have relationship with gastric non-Hodgkin’s lymphoma and gastric mucosa associated with lymphoid tissue lymphoma (MALToma) which can be cured by eradication treatment. H. pylori infection can cause several gastroduodenal pathologies embracing chronic active gastritis, peptic ulcer disease and gastric adenocarcinoma of the antrum. Much attention has been directed to the importance of H. pylori with gastric cancer and then showing positive in serologic tests will lead to high risk of the development of gastric cancer.
Both annexin A2 and A4 (placental anticoagulant protein II) are the members of annexins family. It is well known that overexpression of annexin A2 has been reported in brain, breast, lung, liver, pancreatic, hematologic, colorectal, and gastric carcinoma. Annexin A2 was shown to participate in cell proliferation/differentiation, cell-cell adhesion and the pathogenesis of carcinoma. However, the detailed function of annexin A4 and its relation with the development of cancer are not clear. According to our preliminary data and the literature studies, we proposed possible hypothetical pathways of anne
Keyword(s)
胃癌
蛋白質體
annexin A4
訊息路徑
Gastric cancer
Proteomics
annexin A4
siganl pathway