SPINK1在前列腺癌中的基础及临床转化研究进展

Role of SPINK1 in prostate cancer:advances in experimental and translational research

在肿瘤发生和演进中发挥驱动作用的基因改变常可作为特异性诊断标志物、分子分型的依据和治疗新靶点。丝氨酸蛋白酶抑制因子Kazal1型(SPINK1)又被称为胰腺分泌性胰酶抑制因子(PSTI)或肿瘤相关性胰酶抑制因子(TATI),是一种由56个氨基酸残基组成的分泌性多肽,主要作用是抑制胰蛋白酶原等多种丝氨酸蛋白酶原活性。最近的研究提示,SPINK1可能通过发挥类生长因子作用,促进前列腺癌的生长和侵袭。SPINK1和前列腺癌患者的预后密切相关,可能是某些恶性程度高的前列腺癌的潜在治疗靶点。本课题组研究初步证实SPINK1的过表达与前列腺癌患者的临床不良预后呈正相关。本文通过对现阶段前列腺癌中SPINK1的基础及临床转化研究作简要综述,旨在强调其在前列腺癌的预后评价和治疗靶点选择上的重要意义。

Altered genes that play a driving role in cancer development can often serve as specific diagnostic markers,criteria of molecular classification and therefore potential therapeutic targets.Serine protease inhibitor Kazal type 1（SPINK1）,also known as the pancreatic secretory trypsin inhibitor（PSTI） or the tumor-associated trypsin inhibitor（TATI）,encodes a 56 amino acid secreted peptide,and its normal function is thought to be the inhibition of serine proteases such as trypsin.Recent studies have indicated SPINK1 may act as an autocrine growth factor and promote prostate cancer growth and invasion.The association between SPINK1 expression and adverse prognosis in prostate cancer has been reported.Notably,SPINK1 might be a novel extracellular therapeutic target in a subset of high-grade prostate cancers.Our preliminary data also suggested that overexpression of SPINK1 was significantly correlated with poor prognosis of prostate cancer patients in China.In this review,our group will summarize the current understanding of SPINK1 in experimental and translational research of prostate cancer.Its potential applications in prognostic validation and therapeutic target selection for prostate cancer will be highlighted.