hERG1 Channels and Glut-1 as Independent Prognostic Indicators of Worse Outcome in Stage I and II Colorectal Cancer: A Pilot Study
hERG1 Channels and Glut-1 as Independent Prognostic Indicators of Worse Outcome in Stage I and II Colorectal Cancer: A Pilot Study
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DOI：
10.1593/tlo.11250
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发表时间：
2012-04-01
影响因子：
5
通讯作者：
Arcangeli, Annarosa
中科院分区：
文献类型：
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作者：
Lastraioli, Elena;Bencini, Lapo;Arcangeli, Annarosa
背景：有必要确定新的标志物来评估早期结直肠癌（CRC）患者的复发风险。我们探讨了醚-a-go-go相关基因1通道和一些缺氧标志物对非转移性（I期、II期和III期）CRC患者预后的影响。方法：采用免疫组化方法检测135例患者的hERG1、血管内皮生长因子A （VEGF-A）、葡萄糖转运蛋白1、碳酸酐酶IX （CA-IX）、表皮生长因子受体（EGF-R）、p53的表达。中位随访时间为35个月。评估临床病理参数和总生存期。结果：hERG1与Glut-1、VEGF-A、CA-IX、EGF-R的相关性有统计学意义；p53与VEGF-A、CA-IX；Glut-1与患者年龄有关；EGF-R与TNM和粘蛋白含量有关。在单因素分析中，TNM和CA-IX是预后因素；TNM、hERG1和Glut-1的多变量分析。从最终的多变量模型计算的风险评分允许将患者分为四个不同的风险组：A) I-II期，Glut-1阳性，任何hERG1；B) I-II期，Glut-1和hERG1阴性；C) I-II期，Glut-1阴性，hERG1阳性；D) III期，任何Glut-1和任何hERG1。结论：hERG1阳性与Glut-1阴性可识别I-II期CRC预后不良的患者组。这些患者可能受益于辅助治疗，独立于TNM分期的可能性进行了讨论。影响：淋巴结阴性患者需要更可靠的预后和预测指标，以补充标准的临床和病理分期。
BACKGROUND: There is a need to identify new markers to assess recurrence risk in early-stage colorectal cancer (CRC) patients. We explored the prognostic impact of ether-a-go-go-related gene 1 channels and some hypoxia markers, in patients with nonmetastatic (stage I, II, and III) CRC. METHODS: The expression of hERG1, vascular endothelial growth factor A (VEGF-A), glucose transporter 1, carbonic anhydrase IX (CA-IX), epidermal growth factor receptor (EGF-R), and p53 was tested by immunohistochemistry in 135 patients. The median follow-up was 35 months. Clinicopathologic parameters and overall survival were evaluated. RESULTS: hERG1 displayed a statistically significant association with Glut-1, VEGF-A, CA-IX, and EGF-R; p53 with VEGF-A and CA-IX; Glut-1 with the age of the patients; and EGF-R with TNM and mucin content. TNM and CA-IX were prognostic factors at the univariate analysis; TNM, hERG1, and Glut-1, at the multivariate analysis. Risk scores calculated from the final multivariate model allowed to stratify patients into four different risk groups: A) stage I-II, Glut-1 positivity, any hERG1; B) stage I-II, Glut-1 and hERG1 negativity; C) stage I-II, Glut-1 negativity, hERG1 positivity; D) stage III, any Glut-1 and any hERG1. CONCLUSIONS: hERG1 positivity with Glut-1 negativity identifies a patient group with poor prognosis within stage I-II CRC. The possibility that these patients might benefit from adjuvant therapy, independently from the TNM stage, is discussed. IMPACT: More robust prognostic and predictive markers, supplementing standard clinical and pathologic staging, are needed for node-negative patients.