Ghaneh Paula, Kawesha Anthony, Evans James D, Neoptolemos John P
Department of Surgery, University of Liverpool, 5th Floor UCD Building, Daulby Street, Liverpool, L69 3GA, United Kingdom.
J Hepatobiliary Pancreat Surg. 2002;9(1):1-11. doi: 10.1007/s005340200000.
Pancreatic cancer has a very poor prognosis and is a common cause of cancer death in the Western world. Certain genetic alterations may be important in the prognosis of pancreatic cancer. Activation mutations in the K- ras oncogene occur in around 90% of pancreatic cancers, and the overexpression of growth factors epidermal growth factor (EGF), transforming growth factor (TGF)alpha, TGFbetas 1-3, acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and growth factor receptors c-erbB-2 and -3 and TGFRbetas 1-3 is common. High mutation levels of cell cycle control genes such as p53, p16, p21, SMAD4, and cyclin D1 are found, and there is abnormal expression of apoptotic genes, such as bcl-2, bcl-XL, and bax. The expression of several of these growth factors and their receptors has been found to be associated with poorly differentiated tumors of an advanced stage and decreased survival. However, the inactivation and loss of expression of p16, p53, and p21, and the expression of several apoptotic genes, such as bax and bcl-2, have not been found to be of any prognostic significance. The expression of wild type p53, however, may predict responsiveness to chemotherapy. TGFbeta1 expression has been shown to be associated with longer survival in patients with pancreatic cancer. Two studies (including our own) have found bcl-XL expression to be significantly associated with poor survival. These and newer molecular markers may prove to be important in the choice of future therapies for pancreatic cancer.
胰腺癌的预后非常差，是西方世界癌症死亡的常见原因。某些基因改变可能在胰腺癌的预后中起重要作用。K-ras癌基因的激活突变发生在约90%的胰腺癌中，生长因子表皮生长因子（EGF）、转化生长因子（TGF）α、TGFβ1-3、酸性成纤维细胞生长因子（aFGF）、碱性成纤维细胞生长因子（bFGF）以及生长因子受体c-erbB-2和-3和TGFRβ1-3的过表达很常见。发现细胞周期调控基因如p53、p16、p21、SMAD4和细胞周期蛋白D1的高突变水平，并且凋亡基因如bcl-2、bcl-XL和bax存在异常表达。已发现这些生长因子及其受体中的几种表达与晚期低分化肿瘤和生存率降低有关。然而，尚未发现p16、p53和p21的失活和表达缺失以及几种凋亡基因如bax和bcl-2的表达具有任何预后意义。然而，野生型p53的表达可能预测对化疗的反应性。已表明TGFβ1表达与胰腺癌患者的较长生存期相关。两项研究（包括我们自己的研究）发现bcl-XL表达与不良生存显著相关。这些以及更新的分子标志物可能在未来胰腺癌治疗方法的选择中被证明是重要的。
