The Association between Telomere Length and Cancer Prognosis: Evidence from a Meta-Analysis.
The Association between Telomere Length and Cancer Prognosis: Evidence from a Meta-Analysis.
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端粒长度与癌症预后之间的关联：来自荟萃分析的证据。
DOI：
10.1371/journal.pone.0133174
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hou S
中科院分区：
文献类型：
--
作者：
Zhang C;Chen X;Li L;Zhou Y;Wang C;Hou S
端粒对染色体的完整性和稳定性至关重要。端粒长度（TL）缩短与癌症和衰老相关疾病的风险有关。一些研究探讨了TL和癌症预后之间的关系，但结果相互矛盾。通过检索PubMed（截至2015年5月25日），确定了关于TL与癌症生存期之间关系的前瞻性研究。对癌症类型或DNA来源没有限制。纳入研究的质量采用Newcastle-Ottawa量表进行评估。采用荟萃分析方法确定合并相对风险和95%置信区间。我们的荟萃分析最终纳入了33篇文章，包含45项独立研究，其中27项是关于癌症总体生存率的，18项是关于癌症进展的。短TL与癌症死亡风险增加（RR = 1.30，95%CI：1.06-1.59）和癌症进展不良（RR = 1.44，95%CI：1.10-1.88）相关，两者均具有高度异质性（总生存期I2 = 83.5%，P = 0.012;进展期I2 = 75.4%，P = 0.008）。TL是慢性淋巴细胞白血病患者总体癌症生存和进展的独立预测因子。此外，短端粒还与结直肠癌死亡率增加和食管癌总生存率降低相关，但在其他癌症中不相关。在亚洲和美国人群中，癌症进展与TL相关，在老年人群中，短TL预测癌症生存率低。与肿瘤组织细胞相比，血淋巴细胞中TL的预测效果更好。此外，当仅限于年龄调整的研究，更大的样本量，使用Southern印迹法测量TL或通过风险比估计风险效应时，相关性仍然显着。短TL与癌症生存率低有显著相关性，提示TL具有潜在的预后意义。需要更多的大型设计良好的研究来证实我们的发现。
Telomeres are essential for chromosomal integrity and stability. Shortened telomere length (TL) has been associated with risk of cancers and aging-related diseases. Several studies have explored associations between TL and cancer prognosis, but the results are conflicting. Prospective studies on the relationship between TL and cancer survival were identified by a search of PubMed up to May 25, 2015. There were no restrictions on the cancer type or DNA source. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis approaches were conducted to determine pooled relative risks and 95% confidence intervals. Thirty-three articles containing forty-five independent studies were ultimately involved in our meta-analysis, of which twenty-seven were about overall cancer survival and eighteen were about cancer progression. Short TL was associated with increased cancer mortality risk (RR = 1.30, 95%CI: 1.06–1.59) and poor cancer progression (RR = 1.44, 95%CI: 1.10–1.88), both with high levels of heterogeneity (I2 = 83.5%, P = 0.012for overall survival and I2 = 75.4%, P = 0.008 for progression). TL was an independent predictor of overall cancer survival and progression in chronic lymphocytic leukemia. Besides, short telomeres were also associated with increased colorectal cancer mortality and decreased overall survival of esophageal cancer, but not in other cancers. Cancer progression was associated with TL in Asian and America populations and short TL predicted poor cancer survival in older populations. Compared with tumor tissue cells, TL in blood lymphocyte cells was better for prediction. In addition, the associations remained significant when restricted to studies with adjustments for age, with larger sample sizes, measuring TL using southern blotting or estimating risk effects by hazard ratios. Short TL demonstrated a significant association with poor cancer survival, suggesting the potential prognostic significance of TL. Additional large well-designed studies are needed to confirm our findings.