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肿瘤微环境中胶原特征与 T4N0M0 期结肠癌患者复发和生存的相关性。

Association of the Collagen Signature in the Tumor Microenvironment With Recurrence and Survival of Patients With T4N0M0 Colon Cancer.

机构信息

1 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China 2 School of Science, Jimei University, Xiamen, Fujian, China 3 Department of Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China 4 Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education & Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China.

出版信息

Dis Colon Rectum. 2021 May;64(5):563-575. doi: 10.1097/DCR.0000000000001907.

DOI:10.1097/DCR.0000000000001907
PMID:33538520
Abstract

BACKGROUND

The current clinicopathological risk factors do not accurately predict disease recurrence in patients with T4N0M0 colon cancer. We hypothesized that the collagen signature combined with clinicopathological risk factors (new model) had a better prognostic value than clinicopathological risk factors alone (clinicopathological model).

OBJECTIVE

This study aimed to establish a collagen signature in the tumor microenvironment and to validate its role in predicting the recurrence of T4N0M0 colon cancer.

DESIGN

This was a retrospective study.

SETTINGS

This study took place at a tertiary medical center.

PATIENTS

Patients with T4N0M0 colon cancer who underwent surgery at our center between 2009 and 2015 (n = 416) were included.

INTERVENTION

A total of 142 collagen features were analyzed in the tumor microenvironment in specimens of colon cancer by using second-harmonic generation imaging. A collagen signature was constructed using a least-absolute shrinkage and selection operator Cox regression model.

MAIN OUTCOME MEASURES

The primary outcomes measured were disease-free survival and overall survival.

RESULTS

The training and testing cohorts consisted of 291 and 125 randomly assigned samples, with recurrence rates of 19.9% and 22.4%. A 3-feature-based collagen signature predicted the recurrence risk at 1, 3, and 5 years, with the area under the receiver-operating characteristic curves of 0.808, 0.832, and 0.791 in the training cohort and 0.836, 0.807, and 0.794 in the testing cohort. Multivariate analysis revealed that the collagen signature could independently predict the disease-free survival (HR = 7.17, p < 0.001) and overall survival rates (HR = 5.03, p < 0.001). The new model had a better prognostic value than the clinicopathological model, which included 4 clinicopathological risk factors: obstruction or perforation, lymphovascular invasion, tumor budding, and no chemotherapy.

LIMITATIONS

This study was limited by its retrospective design.

CONCLUSIONS

The collagen signature in the tumor microenvironment may be a new prognostic marker that can effectively predict the recurrence and survival of patients with T4N0M0 colon cancer. See Video Abstract at http://links.lww.com/DCR/B503. ASOCIACIÓN DE LA RÚBRICA DE COLÁGENO EN EL MICROAMBIENTE TUMORAL CON LA RECIDIVA Y LA SOBREVIDA DE PACIENTES CON CÁNCER DE COLON T4N0M0: Los factores de riesgo clínico-patológicos actuales no predicen con precisión la recurrencia de la enfermedad en pacientes con cáncer de colon estadío T4N0M0. Presumimos que la rúbrica de colágeno combinada con factores de riesgo clínico-patológicos (nuevo modelo) tendrían un mejor valor pronóstico que los factores de riesgo clínico-patológicos solos (modelo clínico-patológico).El establecer una rúbrica de colágeno en el microambiente tumoral y validar su papel en la predicción de la recidiva del cáncer de colon T4N0M0.Estudio retrospectivo.Investigación llevada a cabo en un centro médico terciario.Se incluyeron pacientes con cáncer de colon T4N0M0 operados en nuestro centro entre 2009 y 2015 (n = 416).Se analizaron un total de 142 características de colágeno en el microambiente tumoral en muestras de cáncer de colon utilizando imágenes de segunda generación armónica. Se construyó una rúbrica de colágeno utilizando un modelo de regresión LASSO Cox.Sobrevida libre de enfermedad y sobrevida global.Las cohortes de entrenamiento y prueba consistieron en 291 y 125 muestras asignadas al azar, con tasas de recurrencia del 19,9% y 22,4%, respectivamente. La rúbrica del colágeno basada en 3 características predijo el riesgo de recurrencia a 1, 3 y 5 años, con el área bajo las curvas características operativas del receptor de 0,808, 0,832 y 0,791 en la cohorte de entrenamiento y 0,836, 0,807 y 0,794 en la cohorte de prueba, respectivamente. El análisis multivariado reveló que la firma de colágeno podría predecir de forma independiente la supervivencia libre de enfermedad (HR = 7,17, p <0,001) y las tasas de sobrevida general (HR = 5,03, p <0,001). El nuevo modelo tuvo un mejor valor pronóstico que el modelo clínico-patológico, que incluyó cuatro factores de riesgo clínico-patológicos: obstrucción o perforación, invasión linfovascular, gemación tumoral y ausencia de quimioterapia.Este estudio estuvo limitado por su diseño retrospectivo.La rúbrica de colágeno en el microambiente tumoral puede ser un nuevo marcador pronóstico para predecir eficazmente la recurrencia y la subrevida de los pacientes con cáncer de colon T4N0M0. Consulte Video Resumen en http://links.lww.com/DCR/B503. (Traducción-Dr. Xavier Delgadillo).

摘要

背景

目前的临床病理危险因素不能准确预测 T4N0M0 结肠癌患者的疾病复发。我们假设,在肿瘤微环境中建立胶原特征,并验证其在预测 T4N0M0 结肠癌复发中的作用。

目的

本研究旨在建立肿瘤微环境中的胶原特征,并验证其在预测 T4N0M0 结肠癌复发中的作用。

设计

这是一项回顾性研究。

地点

本研究在一家三级医疗中心进行。

患者

纳入 2009 年至 2015 年在我院接受手术的 T4N0M0 结肠癌患者(n=416)。

干预措施

利用二次谐波产生成像技术分析结肠癌标本中 142 种胶原特征。使用最小绝对收缩和选择算子 Cox 回归模型构建胶原特征。

主要观察指标

主要观察指标是无病生存率和总生存率。

结果

训练和测试队列分别包括 291 名和 125 名随机分配的样本,复发率分别为 19.9%和 22.4%。基于 3 个特征的胶原特征预测了 1、3 和 5 年的复发风险,在训练队列中的受试者工作特征曲线下面积为 0.808、0.832 和 0.791,在测试队列中的受试者工作特征曲线下面积为 0.836、0.807 和 0.794。多变量分析显示,胶原特征可独立预测无病生存率(HR=7.17,p<0.001)和总生存率(HR=5.03,p<0.001)。新模型的预后价值优于包括 4 个临床病理危险因素的临床病理模型:梗阻或穿孔、淋巴血管侵犯、肿瘤芽生和无化疗。

局限性

本研究受到其回顾性设计的限制。

结论

肿瘤微环境中的胶原特征可能是一种新的预后标志物,可有效预测 T4N0M0 结肠癌患者的复发和生存。请访问 http://links.lww.com/DCR/B503 查看视频摘要。

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