Department of Pathology, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA.
Curr Pharm Des. 2010 Jun;16(16):1877-81. doi: 10.2174/138161210791208974.
The grim prognosis of lung cancer, that has an overall 10-15% survival at 5 years, remains in the US the leading cause of cancer mortality, provides a compelling rationale for studying the molecular basis of this malignancy. Surmising the common, general association with smoking, lung cancers differ at the microscopic, anatomical, epidemiological and clinical level and harbor complex genetic and epigenetic alterations. Currently, lung cancer is divided into small cell lung carcinoma (SCLC) and non small cell lung carcinoma (NSCLC) for the purpose of clinical management. (NSCLC) constitutes 80-85% of lung cancers and is further divided into histological subtypes such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, etc. The ultimate goal for lung cancer research is to develop a strategy to block the tumor progression and improve the prognosis of lung cancer. This goal can realistically be achieved only when the biological complexity of this disease is taken into account. To this end, identification and understanding of molecular markers that are mechanistically involved in tumor progression is needed. Our recent studies suggest histological subtype-dependent distinct correlations between the expression and/or subcellular localization of tumor suppressive maspin with the progression and prognosis of NSCLC. Maspin is an epithelial specific member of the serine protease inhibitor (serpin) superfamily but recently identified as an endogenous inhibitor of histone deacetylase 1 (HDAC1). This novel biochemical activity coincides with a consensus emerged recently from the evidence that nuclear maspin confers better differentiated epithelial phenotypes, decreased tumor angiogenesis, increased tumor sensitivity to drug-induced apoptosis, and a more favorable prognosis. In the current review, we discuss the evidence that maspin may be a marker that stratifies the progression and prognosis of different subtypes of NSCLC.
肺癌的预后严峻，其 5 年总生存率为 10-15%，仍然是美国癌症死亡的主要原因，这为研究这种恶性肿瘤的分子基础提供了强有力的理由。由于推测与吸烟有共同的一般关联，肺癌在显微镜下、解剖学上、流行病学和临床水平上存在差异，并具有复杂的遗传和表观遗传改变。目前，为了临床管理的目的，肺癌分为小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）。（NSCLC）占肺癌的 80-85%，进一步分为腺癌、鳞状细胞癌和大细胞癌等组织学亚型。肺癌研究的最终目标是开发一种阻止肿瘤进展和改善肺癌预后的策略。只有当考虑到这种疾病的生物学复杂性时，才能实现这一目标。为此，需要确定和了解在肿瘤进展中机械参与的分子标志物。我们最近的研究表明，组织学亚型依赖性的肿瘤抑制因子 maspin 的表达和/或亚细胞定位与 NSCLC 的进展和预后之间存在明显相关性。Maspin 是丝氨酸蛋白酶抑制剂（serpin）超家族中上皮特异性成员，但最近被鉴定为组蛋白去乙酰化酶 1（HDAC1）的内源性抑制剂。这种新的生化活性与最近出现的证据一致，即核 maspin 赋予更好分化的上皮表型、减少肿瘤血管生成、增加肿瘤对药物诱导凋亡的敏感性以及更好的预后。在当前的综述中，我们讨论了 maspin 可能是分层不同亚型 NSCLC 进展和预后的标志物的证据。
