Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma

Preoperative prediction of lymph node (LN) metastasis is accepted as a crucial independent risk factor for treatment decision-making for esophageal squamous cell carcinoma (ESCC) patients. Our study aimed to establish a non-invasive nomogram to identify LN metastasis preoperatively in ESCC patients....

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Main Authors: Tong Liu, Lu-Tao Du, Yun-Shan Wang, Shan-Yu Gao, Juan Li, Pei-Long Li, Zhao-Wei Sun, Helen Binang, Chuan-Xin Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-10-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2020.573501/full
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author Tong Liu
Lu-Tao Du
Lu-Tao Du
Lu-Tao Du
Yun-Shan Wang
Yun-Shan Wang
Yun-Shan Wang
Shan-Yu Gao
Juan Li
Juan Li
Juan Li
Pei-Long Li
Pei-Long Li
Pei-Long Li
Zhao-Wei Sun
Helen Binang
Chuan-Xin Wang
Chuan-Xin Wang
Chuan-Xin Wang
author_facet Tong Liu
Lu-Tao Du
Lu-Tao Du
Lu-Tao Du
Yun-Shan Wang
Yun-Shan Wang
Yun-Shan Wang
Shan-Yu Gao
Juan Li
Juan Li
Juan Li
Pei-Long Li
Pei-Long Li
Pei-Long Li
Zhao-Wei Sun
Helen Binang
Chuan-Xin Wang
Chuan-Xin Wang
Chuan-Xin Wang
author_sort Tong Liu
collection DOAJ
description Preoperative prediction of lymph node (LN) metastasis is accepted as a crucial independent risk factor for treatment decision-making for esophageal squamous cell carcinoma (ESCC) patients. Our study aimed to establish a non-invasive nomogram to identify LN metastasis preoperatively in ESCC patients. Construction of the nomogram involved three sequential phases with independent patient cohorts. In the discovery phase (N = 20), LN metastasis-associated microRNAs (miRNAs) were selected from next-generation sequencing (NGS) assay of human ESCC serum exosome samples. In the training phase (N = 178), a nomogram that incorporated exosomal miRNA model and clinicopathologic was developed by multivariate logistic regression analysis to preoperatively predict LN status. In the validation phase (n = 188), we validated the predicted nomogram's calibration, discrimination, and clinical usefulness. Four differently expressed miRNAs (chr 8-23234-3p, chr 1-17695-5p, chr 8-2743-5p, and miR-432-5p) were tested and selected in the serum exosome samples from ESCC patients who have or do not have LN metastasis. Subsequently, an optimized four-exosomal miRNA model was constructed and validated in the clinical samples, which could effectively identify ESCC patients with LN metastasis, and was significantly superior to preoperative computed tomography (CT) report. In addition, a clinical nomogram consisting of the four-exosomal miRNA model and CT report was established in training cohort, which showed high predictive value in both training and validation cohorts [area under the receiver operating characteristic curve (AUC): 0.880 and 0.869, respectively]. The Hosmer–Lemeshow test and decision curve analysis implied the nomogram's clinical applicability. Our novel non-invasive nomogram is a robust prediction tool with promising clinical potential for preoperative LN metastasis prediction of ESCC patients, especially in T1 stage.
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spelling doaj.art-12e92a5774ce478ba27096ed0409218e2022-12-22T01:48:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-10-011010.3389/fonc.2020.573501573501Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell CarcinomaTong Liu0Lu-Tao Du1Lu-Tao Du2Lu-Tao Du3Yun-Shan Wang4Yun-Shan Wang5Yun-Shan Wang6Shan-Yu Gao7Juan Li8Juan Li9Juan Li10Pei-Long Li11Pei-Long Li12Pei-Long Li13Zhao-Wei Sun14Helen Binang15Chuan-Xin Wang16Chuan-Xin Wang17Chuan-Xin Wang18Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, ChinaShandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, ChinaDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, ChinaShandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, ChinaDepartment of Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, ChinaShandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, ChinaDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, ChinaShandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, ChinaDepartment of Surgery, The Affiliated Hospital of Medical College Qingdao University, Qingdao, ChinaDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, ChinaShandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, ChinaPreoperative prediction of lymph node (LN) metastasis is accepted as a crucial independent risk factor for treatment decision-making for esophageal squamous cell carcinoma (ESCC) patients. Our study aimed to establish a non-invasive nomogram to identify LN metastasis preoperatively in ESCC patients. Construction of the nomogram involved three sequential phases with independent patient cohorts. In the discovery phase (N = 20), LN metastasis-associated microRNAs (miRNAs) were selected from next-generation sequencing (NGS) assay of human ESCC serum exosome samples. In the training phase (N = 178), a nomogram that incorporated exosomal miRNA model and clinicopathologic was developed by multivariate logistic regression analysis to preoperatively predict LN status. In the validation phase (n = 188), we validated the predicted nomogram's calibration, discrimination, and clinical usefulness. Four differently expressed miRNAs (chr 8-23234-3p, chr 1-17695-5p, chr 8-2743-5p, and miR-432-5p) were tested and selected in the serum exosome samples from ESCC patients who have or do not have LN metastasis. Subsequently, an optimized four-exosomal miRNA model was constructed and validated in the clinical samples, which could effectively identify ESCC patients with LN metastasis, and was significantly superior to preoperative computed tomography (CT) report. In addition, a clinical nomogram consisting of the four-exosomal miRNA model and CT report was established in training cohort, which showed high predictive value in both training and validation cohorts [area under the receiver operating characteristic curve (AUC): 0.880 and 0.869, respectively]. The Hosmer–Lemeshow test and decision curve analysis implied the nomogram's clinical applicability. Our novel non-invasive nomogram is a robust prediction tool with promising clinical potential for preoperative LN metastasis prediction of ESCC patients, especially in T1 stage.https://www.frontiersin.org/article/10.3389/fonc.2020.573501/fulllymph node metastasisexosomal biomarkermicroRNAesophageal squamous cell carcinomanomogram
spellingShingle Tong Liu
Lu-Tao Du
Lu-Tao Du
Lu-Tao Du
Yun-Shan Wang
Yun-Shan Wang
Yun-Shan Wang
Shan-Yu Gao
Juan Li
Juan Li
Juan Li
Pei-Long Li
Pei-Long Li
Pei-Long Li
Zhao-Wei Sun
Helen Binang
Chuan-Xin Wang
Chuan-Xin Wang
Chuan-Xin Wang
Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma
Frontiers in Oncology
lymph node metastasis
exosomal biomarker
microRNA
esophageal squamous cell carcinoma
nomogram
title Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma
title_full Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma
title_fullStr Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma
title_full_unstemmed Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma
title_short Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma
title_sort development of a novel serum exosomal microrna nomogram for the preoperative prediction of lymph node metastasis in esophageal squamous cell carcinoma
topic lymph node metastasis
exosomal biomarker
microRNA
esophageal squamous cell carcinoma
nomogram
url https://www.frontiersin.org/article/10.3389/fonc.2020.573501/full
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