Pancreatic Cancer: Clinical Significance of Biomarkers
Pancreatic Cancer: Clinical Significance of Biomarkers
复制标题
胰腺癌：生物标志物的临床意义
DOI：
10.1159/000354996
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Hashizume M,Tanaka M
中科院分区：
文献类型：
--
作者：
Mori M;Chiba T;Nakamizo A;Kumashiro R;Murata M;Akahoshi T;Tomikawa M;Ohuchida K;Ohtsuka T,Mizumoto K;Hashizume M,Tanaka M
背景：胰腺癌患者预后的改善，需要新的有效的筛查诊断策略和治疗方法。胰腺癌发生机制和肿瘤微环境的最新研究进展使我们能够识别用于筛查、诊断和预测癌症治疗的生物标志物，包括针对特定癌症或基质细胞亚群的新疗法。胰腺癌的个性化治疗也很有前景，据报道，S1、卡培他滨和吉西他滨等几种药物具有显著的治疗效果。因此，需要预测标记物来选择最有可能从基于吉西他滨或其他药物的治疗中获益的患者。摘要：我们综述了基于胰腺癌遗传和表观遗传改变以及microRNA异常的有前途的筛查、诊断、预测和预后生物标志物的临床意义。我们还综述了基于胰腺癌微环境中基质细胞（如胰腺星状细胞）的新型生物标志物。最近我们对胰腺癌发生和肿瘤微环境的理解取得了进展，这使得能够识别出可用于筛选、诊断和预测治疗反应的生物标志物，包括针对特定癌细胞亚群的新型药物的反应。虽然基因突变（发现inK-ras，p53和p16ink4a）以及高水平的端粒酶活性经常与胰腺癌相关，但它们作为临床应用的生物标志物的适用性尚未确定。微阵列研究已经确定了几种与胰腺癌相关的蛋白质。其中一些分子，如S100P、MUC1和MUC5AC，可以在血浆和其他体液中被量化，这表明它们作为潜在生物标志物的效用。对吉西他滨耐药的研究已经发现了几个候选标记，包括与吉西他滨代谢和转运相关的基因，这可能为识别那些不能从吉西他滨治疗中获益的患者提供一种手段。MicroRNA （miRNA）分析揭示了一系列差异表达的miRNA：例如，miR-142-5p和miR-204可能是胰腺癌切除术患者对吉西他滨治疗反应的预测因子。由胰腺星状细胞分泌的分子，如CD10和CD271，可能为胰腺癌的细胞特异性治疗提供新的靶点。十二指肠液的使用为胰腺癌筛查提供了一种很有前途的新方法。
Background:Improvement in the prognosis of patients with pancreatic cancer, novel effective screening and diagnostic strategies and treatments are needed. Recent advances in the understanding of pancreatic carcinogenesis and tumor microenvironment have allowed identification of biomarkers for screening, diagnosis and prediction of cancer treatments, including novel therapies targeting specific cancer or stromal cell subpopulations. Personalized therapy in pancreatic cancer is also promising as several drugs such as S1, capecitabine and gemcitabine reportedly have significant therapeutic effects. Predictive markers are thus needed to select patients most likely to benefit from therapies based on gemcitabine or other drugs.Summary:We review the clinical significance of promising screening, diagnostic, predictive and prognostic biomarkers based on genetic and epigenetic alterations and microRNA abnormalities in pancreatic cancer. We also review new types of biomarkers based on stromal cells, such as pancreatic stellate cells, in the microenvironment of pancreatic cancer.Key MessageRecent advances in our understanding of pancreatic carcinogenesis and the tumor microenvironment have enabled the identification of biomarkers that can be used for screening, diagnosis and prediction of therapeutic response, including the response to novel agents targeting specific cancer cell subpopulations.Practical ImplicationsAlthough genetic mutations (found inK-ras,p53andp16INK4A) as well as high levels of telomerase activity are frequently associated with pancreatic cancer, their applicability as biomarkers for clinical use has not yet been established. Microarray studies have identified several proteins related to pancreatic cancer. Several of these molecules, such as S100P, MUC1 and MUC5AC, can be quantified in plasma and other body fluids, indicating their utility as potential biomarkers. Research on gemcitabine resistance has uncovered several candidate markers, including genes related to the metabolism and transport of gemcitabine, which may provide a means for identifying those patients who will not benefit from gemcitabine therapy. MicroRNA (miRNA) profiling has revealed an array of miRNAs that are differentially expressed: for example, miR-142-5p and miR-204 may be predictors of response to gemcitabine-based therapy in patients with resected pancreatic cancer. Molecules secreted by pancreatic stellate cells, such as CD10 and CD271, could provide novel targets for the cell-specific management of pancreatic cancer. The use of duodenal juice provides a promising new approach in pancreatic cancer screening.