| Abstract: | 肺癌 (lung cancer)是致死率極高的惡性腫瘤。依世界衛生組織(World Health Orgnization, WHO)於2015的紀錄，該年肺癌造成了八百八十萬人次的死亡。而非小細胞肺癌(non-small cell lung cancer, NSCLC) 佔據了約80%的肺癌發生率。Connexin43 (Cx43)基因，一般被視為一種腫瘤抑制基因；但其目前在人類肺癌進程中的角色仍然不明。本研究主要目的在探討Cx43基因在肺癌的臨床研究上扮演之角色。
本研究共收集165位非小細胞肺癌病患之腫瘤檢體，利用免疫組織染色以及DNA定序之方法分析病患腫瘤組織中Cx43蛋白的表現量及基因變異。並且將未變異與變異的Cx43基因植入CL-3人類肺癌細胞，來檢視Cx43基因變異對人類肺癌細胞所造成的影響。
本研究結果顯示，在165位非小細胞肺癌患者腫瘤組織中，有14位其腫瘤組織呈現Cx43基因突變；而這些變異伴隨著在腫瘤細胞質與細胞核的Cx43表現蛋白位置異常。將變異Cx43基因轉染至CL-3人類肺癌細胞，可促進此肺癌細胞增生。因此，本研究結果推測原生型Cx43基因可視為非小細胞肺癌之腫瘤抑制基因。而這也是目前已知，第一個將Cx43基因變異與肺癌細胞連結的研究。
依據上述結果推測非小細胞肺癌患者之腫瘤組織中，若出現Cx43基因變異，可以用以預測其病程發展情形。總結本研究之結果將有助於研究者與臨床醫師更了解Cx43基因的表現在非小細胞肺癌病程演進中所扮演的角色，及未來用於發展治療及病況評估的可能性。
Connexin43 (Cx43) gene is a suspected tumor suppressor gene since the re-expressed wild type Cx43 genes reduce the malignancy potential of tumor cells, respectively. However, the role of Cx43 gene expression in human lung tumorigenesis is still unclear. Tumor tissues from 165 primary lung cancer patients were collected to study Cx43 protein expression and gene mutation by immunohistochemistry and direct DNA sequencing. In addition, Cx43 gene with or without mutation were transfected to CL-3 human lung cancer cells to confirm the function of these mutant form Cx43 gene. Our data indicated that aberrant localization of Cx43 protein in the nucleus and cytoplasm of tumor cells was detected in 14 of 165 NSCLC patients. Mutations in the Cx43 gene were also found in patients with aberrant Cx43 localization. After the transfection of these mutant form Cx43 genes into lung cancer cells, the proliferation of these cells was enhanced. Base on our knowledge, this is the first study to show Cx43 gene mutations in human lung neoplasm which substantially supports the hypothesis that the Cx43 gene may act as a tumor suppressor gene, at least in some lung cancer patients. |
