CYP24A1 is an independent prognostic marker of survival in patients with lung adenocarcinoma.
CYP24A1 is an independent prognostic marker of survival in patients with lung adenocarcinoma.
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DOI：
10.1158/1078-0432.ccr-10-1789
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发表时间：
2011-02-15
期刊：
影响因子：
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通讯作者：
Ramnath N
中科院分区：
文献类型：
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作者：
Chen G;Kim SH;King AN;Zhao L;Simpson RU;Christensen PJ;Wang Z;Thomas DG;Giordano TJ;Lin L;Brenner DE;Beer DG;Ramnath N
维生素D的活性形式1 α，25-二羟维生素D3（1，25-D3）在癌症（包括肺腺癌（AC））中发挥抗增殖作用。CYP24A1在许多癌症中过表达并分解代谢1，25-D3。本研究的目的是评估CYP24A1作为预后标志物，并研究其与肺AC细胞中1，25-D3抗增殖活性的相关性。肿瘤和相应的正常标本86例肺AC（阶段I-III）。使用AffymetrixR阵列数据和随后通过定量真实的时间-PCR的确认来确定CYP24 A1 mRNA表达。随后使用101个肺AC的验证集来确认CYP24A1 mRNA表达及其与临床变量的相关性。使用CYP24A1 mRNA高表达和低表达的肺癌细胞系检测1，25-D3的抗增殖作用。CYP24A1 mRNA在肺AC中升高8 - 50倍（与正常非肿瘤性肺相比），在低分化癌中显著更高。5年随访时，生存概率为42%（高CYP 24A1，n = 29）vs 81%（低CYP 24A1，n = 57）（P = 0.007）。101例肿瘤的验证集显示，CYP24 A1是生存的独立预后因素（经年龄、性别和分期校正的多变量考克斯模型，P = 0.001）。与SKLU-1细胞（低CYP24A1）相比，A549细胞（高CYP24A1）对1，25-D3的抗增殖作用更具抗性。CYP24A1过表达与肺AC中较差的存活率相关。这可能与1，25-D3在高表达CYP24A1的肺AC中的抗增殖作用的消除有关。
The active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25-D3) exerts antiproliferative effects in cancers, including lung adenocarcinoma (AC). CYP24A1 is overexpressed in many cancers and catabolizes 1,25-D3. The purpose of our study was to assess CYP24A1 as a prognostic marker and to study its relevance to antiproliferative activity of 1,25-D3 in lung AC cells. Tumors and corresponding normal specimens from 86 patients with lung AC (stages I–III) were available. AffymetrixR array data and subsequent confirmation by quantitative real time-PCR were used to determine CYP24A1 mRNA expression. A subsequent validation set of 101 lung AC was used to confirm CYP24A1 mRNA expression and its associations with clinical variables. The antiproliferative effects of 1,25-D3 were examined using lung cancer cell lines with high as well as low expression of CYP24A1 mRNA. CYP24A1 mRNA was elevated 8–50 fold in lung AC (compared to normal nonneoplastic lung) and significantly higher in poorly-differentiated cancers. At 5 years of follow-up, the probability of survival was 42% (high CYP24A1, n = 29) versus 81% (low CYP24A1, n = 57) (P = 0.007). The validation set of 101 tumors showed that CYP24A1 was independently prognostic of survival (multivariate Cox model adjusted for age, gender and stage, P = 0.001). A549 cells (high CYP24A1) were more resistant to antiproliferative effects of 1,25-D3 compared with SKLU-1 cells (low CYP24A1). CYP24A1 overexpression is associated with poorer survival in lung AC. This may relate to abrogation of antiproliferative effects of 1,25-D3 in high CYP24A1 expressing lung AC.