美国凯特琳癌症研究中心Julio Garcia-Aguilar和Francisco Sanchez-Vega共同合作，近期取得重要工作进展。他们研究探讨了影响直肠癌新辅助治疗反应的基因组和转录组相关决定因素。相关论文2022年8月15日在线发表于《自然—医学》杂志上。

为了确定对新辅助治疗反应的相关性，研究人员分析了738例未经治疗的直肠癌的基因组和转录组谱。APC突变在直肠下部的频率低于中部和上部直肠，这可以解释远端肿瘤更具侵袭性的行为。在治疗不可知的情况下，体细胞改变与新辅助治疗的反应没有显著关联，但KRAS突变与在新辅助放化疗后进行巩固化疗的患者复发更快相关。IGF2和L1CAM的过表达与对新辅助治疗的反应降低有关。对免疫浸润的RNA测序估计确定了一个微卫星稳定的免疫热肿瘤亚群，其反应增加，无病生存期延长。

据介绍，在50岁以下的患者中，直肠癌的发病率呈上升趋势。局部晚期直肠癌仍采用新辅助放疗、化疗和手术治疗，但最近的证据表明，完全缓解的患者可以永久避免手术。

附：英文原文

Title: Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer

Author: Chatila, Walid K., Kim, Jin K., Walch, Henry, Marco, Michael R., Chen, Chin-Tung, Wu, Fan, Omer, Dana M., Khalil, Danny N., Ganesh, Karuna, Qu, Xuan, Luthra, Anisha, Choi, Seo-Hyun, Ho, Yu-Jui, Kundra, Ritika, Groves, Katharine I., Chow, Oliver S., Cercek, Andrea, Weiser, Martin R., Widmar, Maria, Wei, Iris H., Pappou, Emmanouil P., Nash, Garrett M., Paty, Philip B., Shi, Qian, Vakiani, Efsevia, Duygu Selcuklu, S., Donoghue, Mark T. A., Solit, David B., Berger, Michael F., Shia, Jinru, Pelossof, Raphael, Romesser, Paul B., Yaeger, Rona, Smith, J. Joshua, Schultz, Nikolaus, Sanchez-Vega, Francisco, Garcia-Aguilar, Julio

Issue&Volume: 2022-08-15

Abstract: The incidence of rectal cancer is increasing in patients younger than 50years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggests that patients with a complete response can avoid surgery permanently. To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers. APC mutations were less frequent in the lower than in the middle and upper rectum, which could explain the more aggressive behavior of distal tumors. No somatic alterations had significant associations with response to neoadjuvant therapy in a treatment-agnostic manner, but KRAS mutations were associated with faster relapse in patients treated with neoadjuvant chemoradiation followed by consolidative chemotherapy. Overexpression of IGF2 and L1CAM was associated with decreased response to neoadjuvant therapy. RNA-sequencing estimates of immune infiltration identified a subset of microsatellite-stable immune hot tumors with increased response and prolonged disease-free survival.

DOI: 10.1038/s41591-022-01930-z

Source: https://www.nature.com/articles/s41591-022-01930-z