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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Cancer Stem Cell Gene Variants in CD44 Predict Outcome in Stage II and Stage III Colon Cancer Patients
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Cancer Stem Cell Gene Variants in CD44 Predict Outcome in Stage II and Stage III Colon Cancer Patients

机译：CD44中CD44中的癌症干细胞基因变体预测II期和III阶段结肠癌患者的结果

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Background/Aim: Growing evidence suggests that human cancers are stem cell diseases and recent data support the existence of cancer stem cells (CSCs) in a variety of malignancies, including colon cancer. These CSCs were shown to be capable of initiating tumor development and progression. Several studies have suggested CD133, CD26 and CD44 as markers of tumor-initiating cells of colon cancer. The purpose of the present study was to assess the impact of single-nucleotide polymorphisms (SNPs) in stem cell-related genes on clinical outcome in a large cohort of colon cancer patients with clinical stage II and III. Patients and Methods: Data from 599 consecutive patients with colon cancer stage II and III, treated between 1995 and 2011 at a single centre, were retrospectively evaluated. Genomic DNA was extracted from paraffin-embedded normal tissue distant from the tumor to obtain germline DNA. Allelic distribution of polymorphisms was tested for deviation from Hardy-Weinberg equilibrium using x(2)-test. The association of polymorphisms with time to recurrence (TTR) and overall survival (OS) was analyzed using Kaplan-Meier curves and compared by the log-rank test. Case-wise deletion for missing polymorphisms was used in univariable and multivariable analyses. Results: CD44 rs187115 showed a statistically significant association with TTR; patients carrying at least one G allele had a significant reduced risk of recurrence compared to patients with the homozygous A/A variant (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.48-0.94, p=0.019). CD44 rs13347 showed a statistically significant association with OS. Patients carrying at least one T allele in rs13347 had a significantly reduced risk of death compared to patients with the homozygous C/C variant (HR=0.61, 95% CI=0.41-0.92, p=0.019). None of the other investigated polymorphisms (CD44 rs187116, CD44 rs7116432, CD44 rs353639, DPP4 rs2268889, DPP4 rs3788979, DPP4 rs7608798 and CD133 rs2240688) were associated with either TTR or OS. Conclusion: Germline variants rs13347 and rs187115 in the stem cell gene CD44 are prognostically relevant in stage II and III colon cancer patients.
机译：背景/目的：日益增长的证据表明，人类癌症是干细胞疾病，最近的数据支持在包括结肠癌中的各种恶性肿瘤中存在癌症干细胞（CSC）的存在。这些CSC被证明能够启动肿瘤发育和进展。几项研究表明CD133，CD26和CD44作为结肠癌肿瘤引发细胞的标记。本研究的目的是评估单核苷酸多态性（SNP）在干细胞相关基因中对临床癌症患者临床结果的临床结果的影响II和III。患者及方法：回顾性评估了1995年至2011年间患有结肠癌阶段II和III患者的599名患者的数据。从肿瘤远处的石蜡包埋的正常组织中萃取基因组DNA，得到种系DNA。测试多态性的等位基因分布，用于使用X（2） - 最终从Hardy-Weinberg平衡偏差。使用Kaplan-Meier曲线分析多态性与复发时间（TTR）和总存活（OS）的关联进行分析，并通过日志秩检验进行比较。对于缺失多态性的案例明智删除用于单变量和多变量的分析。结果：CD44 RS187115显示与TTR有统计学意义的关联;与纯合A / A变体（HR）= 0.67,95％置信区间（CI）= 0.48-0.94，P = 0.019）相比，携带至少一个G等位基因的患者的复发风险具有显着降低的复发风险。 CD44 RS13347显示了与OS有统计学意义的关联。携带至少一个T级的患者在RS13347中的患者与纯合C / C变体（HR = 0.61,95％CI = 0.41-0.92，P = 0.019）相比，死亡风险显着降低了死亡风险。没有其他调查的多态性（CD44 RS187116，CD44 RS7116432，CD44 RS353639，DPP4 RS226889，DPP4 RS378899，DPP4 RS760898和CD133 RS2240688）与TTR或OS相关。结论：干细胞基因CD44中的种系变体RS13347和RS187115在II期和III阶段癌症患者中预先相关。

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