| 杨成梁,彭良群,罗辉,等.血浆标志物蛋白质组学筛选直肠癌新辅助放化疗疗效的预测指标[J].中华放射医学与防护杂志,2026,46(1):43-49.Yang Chengliang,Peng Liangqun,Luo Hui,et al.Proteomic screening of plasma biomarkers to identify predictive factors for predicting the efficacy of neoadjuvant chemoradiotherapy in rectal cancer[J].Chin J Radiol Med Prot,2026,46(1):43-49 |
| 血浆标志物蛋白质组学筛选直肠癌新辅助放化疗疗效的预测指标 |
| Proteomic screening of plasma biomarkers to identify predictive factors for predicting the efficacy of neoadjuvant chemoradiotherapy in rectal cancer |
| 投稿时间：2024-12-10 |
| DOI：10.3760/cma.j.cn112271-20241210-00471 |
| 中文关键词: 直肠癌 新辅助放化疗 蛋白质组学 疗效评估 生物标志物 |
| 英文关键词:Rectal cancer Neoadjuvant chemoradiotherapy Proteomics Treatment response Biomarker |
| 基金项目: |
| 作者 | 单位 | E-mail | | 杨成梁 | 郑州大学附属肿瘤医院放疗科 河南省卫生健康委员会肿瘤放疗重点实验室, 郑州 450008 | dcluohui@163.com | | 彭良群 | 郑州大学附属肿瘤医院普外科, 郑州 450008 | | | 罗辉 | 郑州大学附属肿瘤医院放疗科 河南省卫生健康委员会肿瘤放疗重点实验室, 郑州 450008 | | | 聂文娜 | 中美(河南)荷美尔肿瘤研究院, 郑州 450003 | | | 刘慧 | 郑州大学基础医学院, 郑州 450001 | | | 张燕平 | 郑州大学附属肿瘤医院放疗科 河南省卫生健康委员会肿瘤放疗重点实验室, 郑州 450008 | | | 徐萌 | 郑州大学附属肿瘤医院放疗科 河南省卫生健康委员会肿瘤放疗重点实验室, 郑州 450008 | | | 王义武 | 郑州大学附属肿瘤医院放疗科 河南省卫生健康委员会肿瘤放疗重点实验室, 郑州 450008 | | | 吴明霞 | 郑州大学附属肿瘤医院放疗科 河南省卫生健康委员会肿瘤放疗重点实验室, 郑州 450008 | | | 葛红 | 郑州大学附属肿瘤医院放疗科 河南省卫生健康委员会肿瘤放疗重点实验室, 郑州 450008 | |
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| 中文摘要: |
| 目的 采用血浆蛋白质组学发掘早期预测直肠癌患者新辅助放化疗疗效的生物标志物。方法 本研究回顾性分析2018年1月至2023年12月在郑州大学附属肿瘤医院确诊为局部进展期直肠腺癌接受新辅助放化疗的患者112例。采集放疗前和放疗开始1周后的血浆标本。依据肿瘤退缩等级(TRG)对所有患者术后组织标本进行病理学分级。采用同位素标记相对和绝对定量(iTRAQ)蛋白质组学方法分析TRG 0级患者的血浆样品,经过生物信息学分析鉴定差异蛋白质;并对关键差异蛋白进行临床血浆标本酶联免疫吸附试验(ELISA)和动物实验验证。结果 19例患者为TRG 0级,其血浆蛋白质组学分析共筛选出439个蛋白质,其中,67个蛋白在放疗后表达上调,31个表达下调。富集分析结果表明,补体级联反应的蛋白质发生了显著的变化(t=2.17~4.93,P＜0.05)。ELISA分析证实TRG 0级和1级患者放疗早期补体水平较TRG2级和3级显著升高(t=4.55~9.01,P＜0.05)。动物实验表明抑制补体降低了放疗疗效(t=3.07,P＜0.05)。结论 在局部进展期直肠癌患者接受新辅助放化疗的过程中,补体途径相关蛋白能够早期预测放疗疗效,血浆补体C3可作为抗肿瘤治疗的潜在参考指标。 |
| 英文摘要: |
| Objective To identify serum-based biomarkers predicting early response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) with proteomics. Methods This study retrospectively analyzed and included 112 patients with newly diagnosed LARC who treated with nCRT in the Affiliated Cancer Hospital of Zhengzhou University from January 2018 to December 2023. Serum was collected prior to treatment and 1 week after nCRT. nCRT treatment response was evaluated post-surgery for all the tumor tissue samples according to tumor regression grade (TRG). The serum samples of patient achieved TRG0 were analyzed using an isobaric tag for relative and absolute quantification-based (iTRAQ) proteomics platform. Differentially expressed proteins were identified by bioinformatics analysis. The key differentially expressed proteins were verified using clinical plasma samples with enzyme-linked immunosorbent assay (ELISA) and animal experiments. Results A total of 19 patients achieved TRG0, who had 439 proteins screened by serum proteomics. Among them, 67 proteins were significantly up-regulated and 31 proteins were significantly down-regulated before and 1 week after nCRT. Enrichment analysis showed that the proteins of complement cascades significantly up-regulated (t = 2.17-4.93, P＜0.05). ELISA analysis confirmed the level of complement in patients with TRG grade 0 and 1 was significantly higher than that in patients with TRG grade 2 and 3 (t = 4.55-9.01, P＜0.05). Animal experiments showed that inhibition of complement reduced the efficacy of radiotherapy (t = 3.07, P＜0.05). Conclusions Complement cascades associated proteins can be used to predict the efficacy of radiotherapy at early phase during the course of nCRT in LARC patients, serum complement C3 can serve as a potential reference indicator for antitumor treatment. |
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