Du Jin-Lin, Li Ge-Nan, He Rong-Wei, Zhang Shi-Zhuo, Zhang Xing, Huang Zhi-Gang
Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, 523808, People's Republic of China.
Department of Hospital Nutrition, First Affiliated Hospital of PLA General Hospital, Beijing, 100048, People's Republic of China.
Onco Targets Ther. 2019 Jun 13;12:4631-4641. doi: 10.2147/OTT.S192362. eCollection 2019.
The chemokine family plays an important role in the growth, invasion, and metastasis of tumors. However, most studies have only focused on a few genes or a few gene loci, and thus could not reveal the associations between functional polymorphisms of chemokine family members and tumor progression. This study aimed to determine the associations between single nucleotide polymorphisms (SNPs) of chemokine family members and the prognosis of esophageal cancer (EC). The Cox risk proportional model and log-rank test were used to analyze the associations of 16 potentially functional SNPs in 13 genes from the chemokine family with the survival of 729 Chinese patients with EC. Prognostic analysis on the 16 SNPs showed that different genotypes of 5 SNPs were associated with patients' survival and the risk of death. Multivariate Cox regression analysis showed that the risk of death was higher in CCL26rs2302009 genotype A/C carriers than in A/A carriers and it was also higher in CX3CL1rs2239352 genotype T/T carriers than in C/C carriers. Stepwise Cox regression analysis showed that CCL26rs2302009 genotype A/C was an independent prognostic factor of EC, and its association with increased risk of death was stronger in patients who were ≤60 years old, female, with tumors located in the middle part of esophagus, with undifferentiated or poorly differentiated tumors, with early-stage pathologic type disease, with the longest diameter of tumor ≤5cm than in their counterparts. These findings suggest that CCL26rs2302009 may be a candidate biomarker for EC and its effect on death risk are associated with the histological grade, pathologic type, and the longest diameter of tumor.
趋化因子家族在肿瘤的生长、侵袭和转移中起着重要作用。然而，大多数研究仅关注少数几个基因或几个基因位点，因此无法揭示趋化因子家族成员的功能多态性与肿瘤进展之间的关联。本研究旨在确定趋化因子家族成员的单核苷酸多态性（SNP）与食管癌（EC）预后之间的关联。采用Cox风险比例模型和对数秩检验分析趋化因子家族13个基因中16个潜在功能性SNP与729例中国EC患者生存情况的相关性。对这16个SNP的预后分析表明，5个SNP的不同基因型与患者的生存及死亡风险相关。多因素Cox回归分析显示，CCL26rs2302009基因型A/C携带者的死亡风险高于A/A携带者，CX3CL1rs2239352基因型T/T携带者的死亡风险高于C/C携带者。逐步Cox回归分析显示，CCL26rs2302009基因型A/C是EC的独立预后因素，与≤60岁、女性、肿瘤位于食管中部、未分化或低分化肿瘤、早期病理类型疾病、肿瘤最长直径≤5cm的患者相比，其与死亡风险增加的关联在这些患者中更强。这些发现表明，CCL26rs2302009可能是EC的候选生物标志物，其对死亡风险的影响与组织学分级、病理类型和肿瘤最长直径有关。
