Peng Honghua, Liu Guifeng, Bao Ying, Zhang Xi, Zhou Lehong, Huang Chenghui, Song Zewen, Cao Sudan, Dang Shiying, Zhang Jing, Huang Tanxiao, Wu Yuling, Xu Mingyan, Song Lele, Cao Peiguo
Department of Oncology, the Third Xiangya Hospital of Central South University, Changsha, China.
The Medical Division, HaploX Biotechnology, Shenzhen, China.
Front Oncol. 2021 Dec 21;11:626190. doi: 10.3389/fonc.2021.626190. eCollection 2021.
Radical or palliative surgery with subsequent adjuvant therapy is the routine treatment for stage II/III colorectal cancer(CRC) and some stage IV CRC patients. This study aimed to clarify the prognostic clinicopathological and genetic factors for these patients.
Fifty-five stage II-IV CRC patients undergoing surgery and adjuvant therapy were recruited, including patients without liver metastasis(5 at stage II, 21 at stage III) and with liver metastasis(29 at stage IV). Genetic alterations of the primary cancer tissues were investigated by whole exome sequencing(WES). Patients were followed up to 1652 days(median at 788 days).
The mutational landscape of primary CRC tissue of patients with or without liver metastasis was largely similar, although the mutational frequency of TRIM77 and TCF7L2 was significantly higher in patients with liver metastasis. Several main driver gene co-mutations, such as TP53-APC, APC-KRAS, APC-FRG1, and exclusive mutations, such as TP53-CREBBP, were found in patients with liver metastasis, but not in patients without liver metastasis. No significant difference was found between the two groups in aberrant pathways. If stage II-IV patients were studied altogether, relapse status, SUPT20HL1 mutations, Amp27_21q22.3 and Del8_10q23.2 were independent risk factors(P<0.05). If patients were divided into two groups by metastatic status, surgery types and Amp6_20q13.33 were independent risk factors for patients without liver metastasis(P<0.05), while TRIM77 mutations were the only independent risk factor for patients with liver metastasis(P<0.05).
Surgery types and Amp6_20q13.33 were independent risk factors for CRC patients without liver metastasis, and TRIM77 mutations were the independent risk factor for CRC patients with liver metastasis.
根治性或姑息性手术联合后续辅助治疗是Ⅱ/Ⅲ期结直肠癌（CRC）及部分Ⅳ期CRC患者的常规治疗方法。本研究旨在明确这些患者的预后相关临床病理及遗传因素。
招募了55例接受手术及辅助治疗的Ⅱ-Ⅳ期CRC患者，包括无肝转移患者（Ⅱ期5例，Ⅲ期21例）和有肝转移患者（Ⅳ期29例）。通过全外显子组测序（WES）研究原发癌组织的基因改变。对患者进行随访，随访时间长达1652天（中位时间为788天）。
有或无肝转移患者的原发CRC组织的突变图谱大体相似，尽管TRIM77和TCF7L2的突变频率在有肝转移患者中显著更高。在有肝转移患者中发现了几种主要的驱动基因共突变，如TP53-APC、APC-KRAS、APC-FRG1，以及特异性突变，如TP53-CREBBP，但在无肝转移患者中未发现。两组在异常通路方面未发现显著差异。如果将Ⅱ-Ⅳ期患者一起研究，复发状态、SUPT20HL1突变、Amp27_21q22.3和Del8_10q23.2是独立危险因素（P<0.05）。如果根据转移状态将患者分为两组，手术类型和Amp6_20q13.33是无肝转移患者的独立危险因素（P<0.05），而TRIM77突变是有肝转移患者的唯一独立危险因素（P<0.05）。
手术类型和Amp6_20q13.33是无肝转移CRC患者的独立危险因素，TRIM77突变是有肝转移CRC患者的独立危险因素。
