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第46卷第5期     杨浚沫,曾奕淙,周 何. 循环肿瘤DNA联合系统性炎症指标预测结直肠癌术后复发的研究进展[J].
                  2026年5月                     南京医科大学学报(自然科学版),2026,46(5):762-770                         ·765 ·


                6,IL⁃6)],通过持续活化核因子κB(nuclear factor of            这些炎症介质能增强肿瘤细胞的膜通透性,进一步
                kappa B,NF⁃κB)与Janus激酶/信号转导及转录激活                  促进 ctDNA 进入血液循环。在ctDNA清除方面,全
                因子 3(Janus kinase/signal transducer and activator of  身性炎症状态可能导致肝、脾等网状内皮系统功能
                transcription 3,JAK/STAT3)等关键通路,直接赋予              紊乱,延缓血中 ctDNA 的清除,延长其在循环中的
                肿瘤细胞侵袭、抗凋亡和异常增殖的能力                   [37] 。更重     半衰期,从而提高检测阳性率。部分基础研究提
                要的是,肿瘤能够募集与极化周围的免疫细胞与基                            示,炎症微环境可能通过影响核酸酶活性或中性粒
                质细胞,将正常的组织修复程序重塑为持续性的病                            细胞胞外诱捕网的形成,参与调控循环DNA的代谢
                理过程。通过利用修复过程中产生的生长因子、促                            与片段化模式。然而,上述机制是否会在CRC患者
                血管生成信号和基质重构,肿瘤成功为自己营造了                            中导致ctDNA 降解加速,进而造成临床检测的假阴
                一个支持其恶性演进和局部扩张的微环境。值得                             性,目前尚缺乏直接证据,值得进一步探究                   [38-39] 。因
                注意的是,炎症微环境不仅促进肿瘤进展,还可能                            此,当患者同时呈现ctDNA 阳性和系统性炎性指标
                直接影响ctDNA 的生物学行为,从而在二者之间形                         升高,这两者可能产生协同作用,从而导致更高的
                成协同作用机制。从机制上来说,炎症微环境可通                            复发风险。
                过以下途径同时促进肿瘤进展并影响 ctDNA:炎症                         3.2  联合应用的临床意义
                因子如 TNF⁃α 和 IL⁃6 可诱导肿瘤细胞发生凋亡、坏                        ctDNA 与系统性炎症指标的联合应用,其核心
                死或 NETosis,从而增加肿瘤 DNA 的释放。同时,                     临床意义在于构建多维度、动态的风险分层体系,

                                                  表1   CRC术后复发预测标志物比较
                          Table 1 Comparative characteristics of biomarkers for predicting postoperative recurrence in CRC
                    Biomarker          ctDNA        Systemic inflammatory indicators  ctDNA+Systemic inflammatory indicators
                Biological essence  Reflects the genomic char⁃ Reflects the systemic immune ⁃ Simultaneously assesses genomic characteristics
                               acteristics of tumors  inflammatory status of the body  and systemic immune⁃inflammatory status,pro⁃
                                                                             viding a more complete pathophysiological view
                Primary detection  NGS,PCR technology  Calculation from peripheral blood Combined application of the above methods
                method                              routine test
                Core advantages  High sensitivity and speci⁃ Low cost,convenient detection,Multi⁃dimensional assessment with complemen⁃
                               ficity;can reveal specific repeatable at high frequency  tary advantages;may achieve higher predictive
                               gene mutations                                value(research is still insufficient)
                Prediction time  May indicate recurrence Dynamic monitoring available,Dynamic combined monitoring may establish the
                window         several months earlier than reflecting real ⁃ time inflammato⁃ optimal warning window for earlier intervention
                               imaging examination  ry load,but the warning time
                                                    window is understudied
                Potential  implica⁃ Guides intensified adju⁃ Identifies inflammatory status,Enables more refined risk stratification,guiding
                tions for treatment vant therapy for MRD⁃posi⁃ suggesting patients who may individualized strategies such as ‘intensified
                decisions      tive patients;guides target⁃ benefit from anti ⁃ inflammatory therapy’,‘de⁃escalation therapy’or‘anti⁃in⁃
                               ed therapy           or immunomodulatory therapy  flammatory combined therapy’
                Primary associated Highly correlated with re⁃ Correlated with both recurrence⁃ May predict recurrence⁃free survival more accu⁃
                prognostic measures currence⁃free survival  free survival and overall survival rately
                Main limitations  High  cost; insufficient Susceptible to non⁃tumor factors High complexity of integrated analysis
                               standardization of detec⁃ such as infection and autoim⁃
                               tion process;affected by mune  diseases; quantification
                               tumor heterogeneity  standards need to be unified
                   The 34 original studies cited in this study were briefly graded using the GRADE evidence quality grading standard. Among them,5 randomized con⁃
                trolled trials were high⁃quality evidence,and 29 cohort studies(including prospective and retrospective cohort studies)were medium⁃quality evidence.
                There was no low⁃quality or very low⁃quality evidence.The overall evidence quality is reliable and can provide effective reference for clinical practice of
                postoperative recurrence prediction of colorectal cancer.
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