切换至 "中华医学电子期刊资源库"

中华结直肠疾病电子杂志 ›› 2021, Vol. 10 ›› Issue (06) : 638 -642. doi: 10.3877/cma.j.issn.2095-3224.2021.06.011

综述

直肠癌新辅助放化疗反应的预测性分子标志物研究进展
黄栋1, 杜金林2,()   
  1. 1. 310058 浙江大学医学院
    2. 321099 金华市中心医院结直肠肛门外科
  • 收稿日期:2021-05-28 出版日期:2021-12-25
  • 通信作者: 杜金林
  • 基金资助:
    金华市科技计划项目(2019-3-004)

Progresses of predictive molecular biomarker for response to neoadjuvant chemoradiation in rectal cancer

Dong Huang1, Jinlin Du2,()   

  1. 1. Zhejiang University School of Medicine, Hangzhou 310058, China
    2. Department of Colorectal and Anal Surgery, Jinhua Municipal Central Hospital Medical Group, Jinhua 321000, China
  • Received:2021-05-28 Published:2021-12-25
  • Corresponding author: Jinlin Du
引用本文:

黄栋, 杜金林. 直肠癌新辅助放化疗反应的预测性分子标志物研究进展[J/OL]. 中华结直肠疾病电子杂志, 2021, 10(06): 638-642.

Dong Huang, Jinlin Du. Progresses of predictive molecular biomarker for response to neoadjuvant chemoradiation in rectal cancer[J/OL]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2021, 10(06): 638-642.

局部进展期直肠癌的标准治疗方案是新辅助放化疗后的根治性手术,但是直肠癌患者对新辅助放化疗的反应表现为从病理完全缓解到无肿瘤消退不等,并且目前尚不清楚不同患者对新辅助放化疗的反应具有如此高的变异性的背后机制。由于应用临床病理和放射学预测新辅助放化疗反应缺乏足够的敏感性和特异性,所以它们的应用具有一定的局限性。此外,虽然分子生物标记物有在早期预测患者对新辅助放化疗的反应的可能,然而因为还没有到达临床水平,所以只有将不同类型的生物标志物,包括临床病理和影像学特征,以及与肿瘤生物学的联系机制一起整合起来,开发出一种最佳的、可靠的生物标志物模型,才能够更准确地预测对新辅助放化疗的反应。在这里,我们回顾了最近在组织和血液为基础的分子生物标志物研究的进展,并阐明它们在预测直肠癌对新辅助放化疗反应方面的潜力。

The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery. However, patients with locally advanced rectal cancer have been shown to present different treatment responses. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. What's more, although molecular biomarkers have the potential to predict response to nCRT at an early time point, none have currently reached the clinic. Hence, only by integrating diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology to develop a sensitive and cost-effective molecular biomarker panel can we predict the response to nCRT accurately. In the present study, we review the recent advance in tissue-and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer.

表1 最常用的肿瘤退化分级(tumor regression grade,TRG)系统
表2 基因表达谱对结直肠癌新辅助放化疗敏感性的预测
[1]
陈万青, 孙可欣, 郑荣寿, 等. 2014年中国分地区恶性肿瘤发病和死亡分析[J]. 中国肿瘤, 2018, 27(1): 1-14.
[2]
杜灵彬, 李辉章, 王悠清, 等. 2013年中国结直肠癌发病与死亡分析[J]. 中华肿瘤杂志, 2017, 39(9): 701-706.
[3]
Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations[J]. Cancer, 1994, 73(11): 2680-2686.
[4]
Dworak O,Keilholz L, and Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy[J]. Int J Colorectal Dis, 1997, 12(1): 19-23.
[5]
Wheeler JM, Warren BF, Mortensen NJ, et al. Quantification of histologic regression of rectal cancer after irradiation: a proposal for a modified staging system[J]. Dis Colon Rectum, 2002, 45(8): 1051-1056.
[6]
Ryan R, Gibbons D, Hyland JM, et al. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer[J]. Histopathology, 2005, 47(2): 141-146.
[7]
Peng H, Wang C, Xiao W, et al. Analysis of Clinical characteristics to predict pathologic complete response for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy[J]. J Cancer, 2018, 9(15): 2687-2692.
[8]
Song J, Huang X, Chen Z, et al. Predictive value of carcinoembryonic antigen and carbohydrate antigen 19-9 related to downstaging to stage 0-I after neoadjuvant chemoradiotherapy in locally advanced rectal cancer[J]. Cancer Manag Res, 2018(10): 3101-3108.
[9]
Dudani S, Marginean H, Tang PA, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictive and prognostic markers in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation[J]. BMC Cancer, 2019, 19(1): 664.
[10]
Rampazzo E, Del Bianco P, Bertorelle R, et al. The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients[J]. Br J Cancer, 2018, 118(6): 878-886.
[11]
Troncarelli Flores BC, Souza E Silva V, Ali Abdallah E, et al. Molecular and kinetic analyses of circulating tumor cells as predictive markers of treatment response in locally advanced rectal cancer patients[J]. Cells, 2019, 8(7): 641.
[12]
Sun W, Huang T, Li G, et al. The advantage of circulating tumor cells over serum carcinoembryonic antigen for predicting treatment responses in rectal cancer[J]. Future Oncol, 2013, 9(10): 1489-1500.
[13]
Sun W, Jia C, Huang T, et al. High-performance size-based microdevice for the detection of circulating tumor cells from peripheral blood in rectal cancer patients[J]. PLoS One, 2013, 8(9): e75865.
[14]
Braun LH, Baumann D, Zwirner K, et al. Neutrophil-to-lymphocyte ratio in rectal cancer-novel biomarker of tumor immunogenicity during radiotherapy or confounding variable?[J]. Int J Mol Sci, 2019, 20(10): 2448.
[15]
Lai S, Huang L, Luo S, et al. Systemic inflammatory indices predict tumor response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer[J]. Oncol Lett, 2020, 20(3): 2763-2770.
[16]
Xiao B, Peng J, Zhang R, et al. Density of CD8+ lymphocytes in biopsy samples combined with the circulating lymphocyte ratio predicts pathologic complete response to chemoradiotherapy for rectal cancer[J]. Cancer Manag Res, 2017, 27(9):701-708.
[17]
Yu J, Lee SH, Jeung TS, et al. Expression of vascular endothelial growth factor as a predictor of complete response for preoperative chemoradiotherapy in rectal cancer[J]. Medicine (Baltimore), 2019, 98(26): e16190.
[18]
Belluco C, Forlin M, Delrio P, et al. Elevated platelet count is a negative predictive and prognostic marker in locally advanced rectal cancer undergoing neoadjuvant chemoradiation: a retrospective multi-institutional study on 965 patients[J]. BMC Cancer, 2018, 18(1): 1094.
[19]
Zhou J, Wang C, Lin G, et al. Serial circulating tumor DNA in predicting and monitoring the effect of neoadjuvant chemoradiotherapy in patients with rectal cancer: A prospective multicenter study[J]. Clin Cancer Res, 2021, 27(1): 301-310.
[20]
曹冬梅, 卢建. 叉头框(Fox)转录因子家族的结构与功能[J]. 生命科学, 2006, 18(5): 491-496.
[21]
Zhang Y, Xu M, Chen J, et al. Prognostic value of the FOXK family expression in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy[J]. Onco Targets Ther, 2020(13): 9185-9201.
[22]
Kamran SC, Lennerz JK, Margolis CA, et al. Integrative molecular characterization of resistance to neoadjuvant chemoradiation in rectal cancer[J]. Clin Cancer Res, 2019, 25(18): 5561-5571.
[23]
Wan JF, Li XQ, Zhang J, et al. Aneuploidy of chromosome 8 and mutation of circulating tumor cells predict pathologic complete response in the treatment of locally advanced rectal cancer[J]. Oncol Lett, 2018, 16(2): 1863-1868.
[24]
do Canto LM, Barros-Filho MC, Rainho CA, et al. Comprehensive analysis of DNA methylation and prediction of response to neoadjuvant therapy in locally advanced rectal cancer[J]. Cancers (Basel), 2020, 12(11): 3079.
[25]
Machackova T, Trachtova K, Prochazka V, et al. Tumor microRNAs identified by small RNA sequencing as potential response predictors in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy[J]. Cancer Genomics Proteomics, 2020, 17(3): 249-257.
[26]
Cristóbal I, Rubio J, Santos A, et al. MicroRNA-199b downregulation confers resistance to 5-fluorouracil treatment and predicts poor outcome and response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients[J]. Cancers (Basel), 2020, 12(6): 1655.
[27]
Du B, Wang X, Wu D, et al. MicroRNA expression profiles identify biomarkers for predicting the response to chemoradiotherapy in rectal cancer[J]. Mol Med Rep, 2018, 18(2): 1909-1916.
[28]
Campayo M, Navarro A, Benítez JC, et al. miR-21, miR-99b and miR-375 combination as predictive response signature for preoperative chemoradiotherapy in rectal cancer[J]. PLoS One, 2018, 13(11): e0206542.
[29]
Yokoyama Y, Sakatani T, Wada R, et al. In vitro and in vivo studies on the association of long non-coding RNAs H19 and urothelial cancer associated 1 with the susceptibility to 5-fluorouracil in rectal cancer[J]. Int J Oncol, 2019, 55(6): 1361-1371.
[30]
Ma WJ, Gu YK, Peng JH, et al. Pretreatment TACC3 expression in locally advanced rectal cancer decreases the response to neoadjuvant chemoradiotherapy[J]. Aging (Albany NY), 2018, 10(10): 2755-2771.
[31]
Chang IW, Liu KW, Ragunanan M, et al. SERPINB5 Expression: Association with CCRT response and prognostic value in rectal cancer[J]. Int J Med Sci, 2018, 15(4): 376-384.
[32]
Ferrandon S, DeVecchio J, Duraes L, et al. CoA synthase (COASY) mediates radiation resistance via PI3K signaling in rectal cancer[J]. Cancer Res, 2020, 80(2): 334-346.
[33]
Yan X, Chen J, Meng Y, et al. RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase-9-caspase-3-dependent apoptotic pathway[J]. Cancer Med, 2019, 8(6): 3094-3104.
[34]
Zhang RX, Zhou ZG, Lu SX, et al. Pim-3 as a potential predictor of chemoradiotherapy resistance in locally advanced rectal cancer patients[J]. Sci Rep, 2017, 7(1): 16043.
[35]
Bowden DL, Sutton PA, Wall MA, et al. Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response[J]. J Proteomics, 2018(179): 53-60.
[36]
Martinez-Useros J, Moreno I, Fernandez-Aceñero MJ, et al. The potential predictive value of DEK expression for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer[J]. BMC Cancer, 2018, 18(1):144.
[37]
Kim JY, Park SG, Kim KS, et al. The Krüppel-like factor (KLF5) as a predictive biomarker in preoperative chemoradiation therapy for rectal cancer[J]. Ann Surg Treat Res, 2019, 97(2): 83-92.
[38]
Akiyoshi T, Tanaka N, Kiyotani K, et al. Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer[J]. Br J Surg, 2019, 106(10): 1381-1392.
[39]
Matsutani S, Shibutani M, Maeda K, et al. Significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer[J]. Cancer Sci, 2018, 109(4): 966-979.
[40]
Hasan S, Renz P, Wegner RE, et al. Microsatellite instability (MSI) as an independent predictor of pathologic complete response (PCR) in locally advanced rectal cancer: A national cancer database (NCDB) analysis[J]. Ann Surg, 2020, 271(4): 716-723.
[41]
Jimenez L, Perez RO, São Julião GP, et al. Prediction of poor response to neoadjuvant chemoradiation in patients with rectal cancer using a DNA repair deregulation score: picking the losers instead of the winners[J]. Dis Colon Rectum, 2020, 63(3): 300-309.
[42]
Peng J, Ma W, Zhou Z, et al. Genetic variations in the PI3K/PTEN/AKT/mTOR pathway predict tumor response and disease-free survival in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy and radical surgery[J]. J Cancer, 2018, 9(6): 1067-1077.
[43]
Chao X, Wang Z, Lu S, et al. Signet ring cell component in pretreatment biopsy predicts pathological response to preoperative chemoradiotherapy in rectal cancer[J]. Int J Clin Oncol, 2020, 25(9): 1653-1662.
[44]
Sottoriva A, Kang H, Ma Z, et al. A Big Bang model of human colorectal tumor growth[J]. Nat Genet, 2015, 47(3): 209-216.
[1] 赵丽霞, 王春霞, 陈一锋, 胡东平, 张维胜, 王涛, 张洪来. 内脏型肥胖对腹腔镜直肠癌根治术后早期并发症的影响[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 35-39.
[2] 吴晖, 佴永军, 施雪松, 魏晓为. 两种解剖入路下行直肠癌侧方淋巴结清扫的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 40-43.
[3] 周世振, 朱兴亚, 袁庆港, 刘理想, 王凯, 缪骥, 丁超, 汪灏, 管文贤. 吲哚菁绿荧光成像技术在腹腔镜直肠癌侧方淋巴结清扫中的应用效果分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 44-47.
[4] 奚玲, 仝瀚文, 缪骥, 毛永欢, 沈晓菲, 杜峻峰, 刘晔. 基于肌少症构建的造口旁疝危险因素预测模型[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 48-51.
[5] 徐逸男. 不同术式治疗梗阻性左半结直肠癌的疗效观察[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 72-75.
[6] 李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
[7] 郑民华, 蒋天宇, 赵轩, 马君俊. 中国腹腔镜直肠癌根治术30年发展历程与未来[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 591-595.
[8] 池畔, 黄胜辉. 中国腹腔镜直肠癌根治术30年来的巨大进步[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 596-600.
[9] 李明, 屠松, 闫鹏, 钱军, 高鹏程, 许文山, 杨发英, 胡振涛, 单永玮. 应用前列腺电切镜引导置管治疗直肠低位吻合口漏研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 603-606.
[10] 李玲, 刘亚, 李培玲, 张秀敏, 李萍. 直肠癌患者术后肠道菌群的变化与抑郁症相关性研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 607-610.
[11] 赵梓竣, 兰运升. 改良一针法末端回肠造口术对低位直肠癌保肛术后应激反应及安全性的影响[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 611-614.
[12] 吴胜伟, 王志伟, 陈贵进, 刘序, 吴晓翔. 系膜肥厚低位直肠癌患者改良NOSES Ⅰ式手术的临床效果评价[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 615-618.
[13] 韦巧玲, 黄妍, 赵昌, 宋庆峰, 陈祖毅, 黄莹, 蒙嫦, 黄靖. 肝癌微波消融术后中重度疼痛风险预测列线图模型构建及验证[J/OL]. 中华临床医师杂志(电子版), 2024, 18(08): 715-721.
[14] 蔡晓雯, 李慧景, 丘婕, 杨翼帆, 吴素贤, 林玉彤, 何秋娜. 肝癌患者肝动脉化疗栓塞术后疼痛风险预测模型的构建及验证[J/OL]. 中华临床医师杂志(电子版), 2024, 18(08): 722-728.
[15] 王誉英, 刘世伟, 王睿, 曾娅玲, 涂禧慧, 张蒲蓉. 老年乳腺癌新辅助治疗病理完全缓解的预测因素分析[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 641-646.
阅读次数
全文


摘要