HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome.
HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome.
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DOI：
10.1186/1746-1596-9-78
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发表时间：
2014-04-07
影响因子：
2.6
通讯作者：
Jirström K
中科院分区：
文献类型：
--
作者：
Bengtsson E;Nerjovaj P;Wangefjord S;Nodin B;Eberhard J;Uhlén M;Borgquist S;Jirström K
肿瘤特异性HMG-CoA还原酶（HMGCR）表达与良好预后之间的关联先前已在乳腺癌和卵巢癌中得到证实。本研究旨在探讨HMGCR在结直肠癌中的表达、临床病理学相关性及预后价值。在马尔默饮食和癌症研究中，对来自557例结肠直肠癌发病病例的原发性肿瘤组织微阵列中HMGCR的免疫组织化学表达进行了评估。应用Pearson卡方检验探讨HMGCR表达与临床病理因素和其他研究生物标志物之间的关系。根据HMGCR表达阴性与阳性，使用Kaplan Meier分析和考克斯比例风险模型来评估HMGCR表达与癌症特异性生存期（CSS）之间的关系。共有535例（96.0%）肿瘤适合分析，其中61例（11.4%）为HMGCR阴性。胞浆HMGCR阳性表达与诊断时无远处转移（p = 0.002）、无血管浸润（p = 0.043）、微卫星不稳定性（p = 0.033）、细胞周期蛋白D1（p = <0.001）和p21（p = <0.001）表达相关。在整个队列（HR = 1.79; 95% CI 1.20-2.66）和III-IV期疾病（HR = 1.71; 95% CI 1.09-2.68）的未校正考克斯回归分析中，HMGCR阳性表达与CSS延长显著相关，但在校正已确定的临床病理学参数后则不相关。这项前瞻性队列研究的结果表明，HMGCR在结直肠癌中差异表达，阳性表达与良好的肿瘤特征和未校正分析中的生存期延长相关。HMGCR作为结直肠癌新辅助或辅助他汀类药物治疗反应的预测因子的效用值得进一步研究。本文的虚拟幻灯片可以在这里找到：http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464。
An association between tumor-specific HMG-CoA reductase (HMGCR) expression and good prognosis has previously been demonstrated in breast and ovarian cancer. In this study, the expression, clinicopathological correlates and prognostic value of HMGCR expression in colorectal cancer was examined. Immunohistochemical expression of HMGCR was assessed in tissue microarrays with primary tumours from 557 incident cases of colorectal cancer in the Malmö Diet and Cancer Study. Pearson’s Chi Square test was applied to explore the associations between HMGCR expression and clinicopathological factors and other investigative biomarkers. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the relationship between HMGCR expression and cancer-specific survival (CSS) according to negative vs positive HMGCR expression. A total number of 535 (96.0%) tumours were suitable for analysis, of which 61 (11.4%) were HMGCR negative. Positive cytoplasmic HMGCR expression was associated with distant metastasis-free disease at diagnosis (p = 0.002), lack of vascular invasion (p = 0.043), microsatellite-instability (p = 0.033), expression of cyclin D1 (p = <0.001) and p21 (p = <0.001). Positive HMGCR expression was significantly associated with a prolonged CSS in unadjusted Cox regression analysis in the entire cohort (HR = 1.79; 95% CI 1.20-2.66) and in Stage III-IV disease (HR = 1.71; 95% CI 1.09-2.68), but not after adjustment for established clinicopathological parameters. Findings from this prospective cohort study demonstrate that HMGCR is differentially expressed in colorectal cancer and that positive expression is associated with favourable tumour characteristics and a prolonged survival in unadjusted analysis. The utility of HMGCR as a predictor of response to neoadjuvant or adjuvant statin treatment in colorectal cancer merits further study. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464.
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影响因子：
8.8
作者：
Larsson, A.;Johansson, M. E.;Wangefjord, S.;Gaber, A.;Nodin, B.;Kucharzewska, P.;Welinder, C.;Belting, M.;Eberhard, J.;Johnsson, A.;Uhlen, M.;Jirstrom, K.
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