1231例结直肠癌类器官培养成功率的影响因素分析

Analysis of factors influencing the success rate of organoid culture in 1231 cases of colorectal cancer

目的探讨影响结直肠癌类器官培养成功率的因素。方法本研究采用回顾性观察性研究方法。回顾性收集2021年12月至2022年11月期间,在南方医科大学南方医院接受手术或活检且未合并其他恶性肿瘤的结直肠癌患者的肿瘤组织标本进行类器官培养,包括1130例结直肠癌患者共1231份肿瘤组织样本。采用单因素分析和多因素Logistic回归分析影响结直肠癌类器官培养成功率的因素。结果本组标本培养中位时间为7(3~12)d。总培养成功率为76.3%(939/1231)。不同取材部位的类器官培养成功率不同,其中恶性腹水成功率最高(96.4%,27/28),其后依次为肝转移灶(83.1%,54/65)、肺转移灶(8/10)、原发灶(76.0%,816/1074)、网膜转移灶(10/14)、腹膜转移灶(61.5%,16/26)、卵巢转移灶(3/5)和淋巴结转移灶(5/9);原发灶类器官培养成功率低于恶性腹水类器官培养成功率比较,差异有统计学意义(P=0.012),而与其他转移灶的类器官培养成功率差异无统计学意义(均P>0.05)。腹腔穿刺获取恶性腹水的类器官培养成功率为96.4%(27/28),手术标本的类器官培养成功率为76.5%(864/1130),内镜活检标本的类器官培养成功率为65.8%(48/73),差异有统计学意义(χ^(2)=10.773,P=0.005)。新辅助放化疗组的类器官培养成功率为62.5%(40/64),低于无辅助治疗组(76.9%,787/1023)和单纯化疗组(77.8%,112/144),差异有统计学意义(χ^(2)=7.134,P=0.028)。多因素Logistic分析显示,内镜活检(OR=0.557,95%CI:0.335~0.924,P=0.024)和新辅助放化疗(OR=0.483,95%CI:0.285~0.820,P=0.007)是影响结直肠癌类器官培养成功率的独立危险因素;恶性腹水(OR=8.537,95%CI:1.154~63.131,P=0.036)和腹腔穿刺(OR=8.294,95%CI:1.112~61.882,P=0.039)是影响结直肠癌类器官培养成功率的独立保护因素。结论结直肠癌类器官的培养成功率受取材部位、取材方式及新辅助治疗的影响,取材来自内镜活检和术前接受新辅助放化疗者培养成功率较低,取材来自恶性腹水者培养成功率较高。建议怀疑腹膜转移者首选恶性腹水培养。

Objective To investigate the risk factors for organoid culture failure in colorectal cancer.Methods This was a retrospective observational study.Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022.Organoid culture was performed on 1231 tumor tissue samples.Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples.Results The median(range)duration of organoid culture was 7(3–12)days.The overall rate of successful culture was 76.3%(939/1231).The rate of successful organoid cultures varied according to the sampling site,malignant ascites having the highest success rate(96.4%,27/28),followed by liver metastases(83.1%,54/65),lung metastases(8/10),primary tumors(76.0%,816/1074),omental metastases(10/14),peritoneal metastases(61.5%,16/26),ovarian metastases(3/5),and lymph node metastases(5/9).The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant(P=0.012),whereas none of the other rates of successful organoid culture success differed significantly(all P>0.05).The rate of successful organoid culture was 96.4%(27/28)for malignant ascites obtained by abdominal puncture,76.5%(864/1130)for surgical specimens,and 65.8%(48/73)for endoscopic biopsies;these differences are statistically significant(χ^(2)=10.773,P=0.005).The rate of successful organoid culture was 62.5%(40/64)in the neoadjuvant chemoradiotherapy group,which is significantly lower than in the non-adjuvant(76.9%,787/1023)and chemotherapy groups(77.8%,112/144)(χ^(2)=7.134,P=0.028).Multivariate logistic regression analysis revealed that endoscopic biopsy(OR=0.557,95%CI:0.335–0.924,P=0.024)and neoadjuvant chemoradiotherapy(OR=0.483,95%CI:0.285–0.820,P=0.007)were independent risk factors for failure of organoid culture of colorectal cancer samples.Malignant ascites(OR=8.537,95%CI:1.154–63.131,P=0.036)and abdominal puncture(OR=8.294,95%CI:1.112–61.882,P=0.039)were identified as independent protective factors.Conclusions The rate of successful organoid culture was influenced by the sampling site,sampling method,and chemoradiotherapy.The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy,and higher for malignant ascites.We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.