背景:MCP-1/CCR2轴是在肿瘤微环境中起关键作用的主要趋化因子信号通路之一,并参与触发各种肿瘤进展机制,如增加免疫抑制细胞募集,促进肿瘤细胞增殖和侵袭。
目的:本研究调查了MCP1(rs1024611)和CCR2(rs1799864)基因变异与结直肠癌(CRC)和结直肠癌肝转移(CRLM)的风险和预后的关系。
方法:一项回顾性队列研究涉及408例患者(284例CRC和124例CRLM),进行了284例健康对照。通过PCR-RFLP测定进行所选多态性的基因分型,并通过微芯片和毛细管电泳进行确认。
结果:结果强调了MCP1rs1024611(非AA)和CCR2rs1799864(GA)基因型与CRC和CRLM风险增加之间的正相关。SNP与临床病理特征之间的相关性显示,MCP1rs1024611和CCR2rs1799864(显性模型)与CRC不良预后特征之间存在正相关。Kaplan-Meier生存分析显示,MCP1rs1024611非AA携带者与降低的生存率之间存在显着关联。新辅助治疗显示MCP1和CCR2野生型基因型携带者的CRC和CRLM存活率提高。对于携带MCP1和CCR2多态性突变基因型的患者,FOLFIRI化疗显示降低的生存率。
结论:考虑到我们的结果,我们认为,MCP1和CCR2多态性可能构成CRC和CRLM发生的独立因素,并可能成为有效治疗方法的有用靶点.
The MCP-1/CCR2 axis is one of the major chemokine signaling pathways that play a crucial role in the tumor microenvironment and has been involved in triggering various tumor progression mechanisms, such as increasing the immunosuppressive cells recruitment and promoting tumor cell proliferation and invasiveness.
The current study investigated the association of MCP1 (rs1024611) and CCR2 (rs1799864) genes variants with the risk as well as prognosis of colorectal cancer (CRC) and colorectal liver metastases (CRLM).
A retrospective cohort study involved 408 patients (284 CRC and 124 CRLM), and 284 healthy control was conducted. Genotyping of selected polymorphisms was performed by PCR-RFLP assays and confirmed by microchip and capillary electrophoresis.
The results highlighted a positive association between MCP1 rs1024611 (non-AA) and CCR2 rs1799864 (GA) genotypes with increased CRC and CRLM risk. Correlation between SNPs and clinicopathological characteristics revealed a positive association between MCP1 rs1024611 and CCR2 rs1799864 (dominant model) and CRC poor prognosis features. Kaplan-Meier survival analysis revealed a significant association between MCP1 rs1024611 non-AA carriers and decreased survival rate. Neoadjuvant treatment showed an improvement in CRC and CRLM survival rates among carriers of MCP1 and CCR2 wild-type genotype. FOLFIRI chemotherapy exhibits reduced survival rates for patients who carried mutated genotypes of MCP1 and CCR2 polymorphisms.
Considering our results, we suggest That both MCP1 and CCR2 polymorphisms may constitute independent factors for CRC and CRLM occurrence and can be helpful targets for an efficient therapeutic approach.