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24-04-2024 | Gastric Cancer | Hollow Organ GI

Epstein–Barr virus positive gastric cancer: the pathological basis of CT findings and radiomics models prediction

Authors: Shuangshuang Sun, Lin Li, Mengying Xu, Ying Wei, Feng Shi, Song Liu

Published in: Abdominal Radiology

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Abstract

Purpose

To analyze the clinicopathologic information and CT imaging features of Epstein–Barr virus (EBV)-positive gastric cancer (GC) and establish CT-based radiomics models to predict the EBV status of GC.

Methods

This retrospective study included 144 GC cases, including 48 EBV-positive cases. Pathological and immunohistochemical information was collected. CT enlarged LN and morphological characteristics were also assessed. Radiomics models were constructed to predict the EBV status, including decision tree (DT), logistic regression (LR), random forest (RF), and support vector machine (SVM).

Results

T stage, Lauren classification, histological differentiation, nerve invasion, VEGFR2, E-cadherin, PD-L1, and Ki67 differed significantly between the EBV-positive and -negative groups (p = 0.015, 0.030, 0.006, 0.022, 0.028, 0.030, < 0.001, and < 0.001, respectively). CT enlarged LN and large ulceration differed significantly between the two groups (p = 0.019 and 0.043, respectively). The number of patients in the training and validation cohorts was 100 (with 33 EBV-positive cases) and 44 (with 15 EBV-positive cases). In the training cohort, the radiomics models using DT, LR, RF, and SVM yielded areas under the curve (AUCs) of 0.905, 0.771, 0.836, and 0.886, respectively. In the validation cohort, the diagnostic efficacy of radiomics models using the four classifiers were 0.737, 0.722, 0.751, and 0.713, respectively.

Conclusion

A significantly higher proportion of CT enlarged LN and a significantly lower proportion of large ulceration were found in EBV-positive GC. The prediction efficiency of radiomics models with different classifiers to predict EBV status in GC was good.

Graphical Abstract

Appendix
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Literature
1.
go back to reference Sung H, Ferlay J, Siegel RL, et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209-249.CrossRefPubMed Sung H, Ferlay J, Siegel RL, et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209-249.CrossRefPubMed
2.
go back to reference Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202-209.CrossRef Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202-209.CrossRef
3.
go back to reference van Beek J, zur Hausen A, Klein Kranenbarg E, et al (2004) EBV-Positive Gastric Adenocarcinomas: A Distinct Clinicopathologic Entity With a Low Frequency of Lymph Node Involvement. Journal of Clinical Oncology 22:664-670.CrossRefPubMed van Beek J, zur Hausen A, Klein Kranenbarg E, et al (2004) EBV-Positive Gastric Adenocarcinomas: A Distinct Clinicopathologic Entity With a Low Frequency of Lymph Node Involvement. Journal of Clinical Oncology 22:664-670.CrossRefPubMed
4.
go back to reference Tan P, Yeoh KG (2015) Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma. Gastroenterology 149:1153-1162 e1153.CrossRef Tan P, Yeoh KG (2015) Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma. Gastroenterology 149:1153-1162 e1153.CrossRef
5.
go back to reference Muti HS, Heij LR, Keller G, et al (2021) Development and validation of deep learning classifiers to detect Epstein-Barr virus and microsatellite instability status in gastric cancer: a retrospective multicentre cohort study. Lancet Digit Health 3:e654-e664.CrossRefPubMedPubMedCentral Muti HS, Heij LR, Keller G, et al (2021) Development and validation of deep learning classifiers to detect Epstein-Barr virus and microsatellite instability status in gastric cancer: a retrospective multicentre cohort study. Lancet Digit Health 3:e654-e664.CrossRefPubMedPubMedCentral
6.
go back to reference Kim ST, Cristescu R, Bass AJ, et al (2018) Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nature Medicine 24:1449-1458.CrossRefPubMed Kim ST, Cristescu R, Bass AJ, et al (2018) Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nature Medicine 24:1449-1458.CrossRefPubMed
7.
go back to reference Kim SY, Park C, Kim H-J, et al (2015) Deregulation of Immune Response Genes in Patients With Epstein-Barr Virus-Associated Gastric Cancer and Outcomes. Gastroenterology 148:137-147.e139.CrossRefPubMed Kim SY, Park C, Kim H-J, et al (2015) Deregulation of Immune Response Genes in Patients With Epstein-Barr Virus-Associated Gastric Cancer and Outcomes. Gastroenterology 148:137-147.e139.CrossRefPubMed
8.
go back to reference Ajani JA, D’Amico TA, Bentrem DJ, et al (2022) Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 20:167-192.CrossRefPubMed Ajani JA, D’Amico TA, Bentrem DJ, et al (2022) Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 20:167-192.CrossRefPubMed
10.
go back to reference Zheng X, Wang R, Zhang X, et al (2022) A deep learning model and human-machine fusion for prediction of EBV-associated gastric cancer from histopathology. Nat Commun 13:2790.CrossRefPubMedPubMedCentral Zheng X, Wang R, Zhang X, et al (2022) A deep learning model and human-machine fusion for prediction of EBV-associated gastric cancer from histopathology. Nat Commun 13:2790.CrossRefPubMedPubMedCentral
11.
go back to reference Chen Y, Yuan F, Wang L, et al (2022) Evaluation of dual-energy CT derived radiomics signatures in predicting outcomes in patients with advanced gastric cancer after neoadjuvant chemotherapy. Eur J Surg Oncol 48:339-347.CrossRefPubMed Chen Y, Yuan F, Wang L, et al (2022) Evaluation of dual-energy CT derived radiomics signatures in predicting outcomes in patients with advanced gastric cancer after neoadjuvant chemotherapy. Eur J Surg Oncol 48:339-347.CrossRefPubMed
12.
go back to reference Dong D, Tang L, Li ZY, et al (2019) Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer. Ann Oncol 30:431-438.CrossRefPubMedPubMedCentral Dong D, Tang L, Li ZY, et al (2019) Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer. Ann Oncol 30:431-438.CrossRefPubMedPubMedCentral
13.
go back to reference Huang H, Xu F, Chen Q, Hu H, Qi F, Zhao J (2022) The value of CT-based radiomics nomogram in differential diagnosis of different histological types of gastric cancer. Phys Eng Sci Med 45:1063-1071.CrossRefPubMedPubMedCentral Huang H, Xu F, Chen Q, Hu H, Qi F, Zhao J (2022) The value of CT-based radiomics nomogram in differential diagnosis of different histological types of gastric cancer. Phys Eng Sci Med 45:1063-1071.CrossRefPubMedPubMedCentral
14.
go back to reference Zhao H, Li W, Lyu P, et al (2021) TCGA-TCIA-Based CT Radiomics Study for Noninvasively Predicting Epstein-Barr Virus Status in Gastric Cancer. AJR Am J Roentgenol 217:124-134.CrossRefPubMed Zhao H, Li W, Lyu P, et al (2021) TCGA-TCIA-Based CT Radiomics Study for Noninvasively Predicting Epstein-Barr Virus Status in Gastric Cancer. AJR Am J Roentgenol 217:124-134.CrossRefPubMed
15.
go back to reference Zhang C, Wen HL, Zhang R, Xie SY, Xie CM (2022) Computed tomography radiomics to predict EBER positivity in Epstein-Barr virus-associated gastric adenocarcinomas: a retrospective study. Acta Radiol 63:1005-1013.CrossRefPubMed Zhang C, Wen HL, Zhang R, Xie SY, Xie CM (2022) Computed tomography radiomics to predict EBER positivity in Epstein-Barr virus-associated gastric adenocarcinomas: a retrospective study. Acta Radiol 63:1005-1013.CrossRefPubMed
16.
go back to reference Kim HJ, Kim AY, Oh ST, et al (2005) Gastric cancer staging at multi-detector row CT gastrography: comparison of transverse and volumetric CT scanning. Radiology 236:879–85.CrossRefPubMed Kim HJ, Kim AY, Oh ST, et al (2005) Gastric cancer staging at multi-detector row CT gastrography: comparison of transverse and volumetric CT scanning. Radiology 236:879–85.CrossRefPubMed
17.
go back to reference Chamadol N, Wongwiwatchai J, Bhudhisawasd V, Pairojkul C (2008) Accuracy of spiral CT in preoperative staging of gastric carcinoma: correlation with surgical and pathological findings. J Med Assoc Thai 91:356-363.PubMed Chamadol N, Wongwiwatchai J, Bhudhisawasd V, Pairojkul C (2008) Accuracy of spiral CT in preoperative staging of gastric carcinoma: correlation with surgical and pathological findings. J Med Assoc Thai 91:356-363.PubMed
18.
go back to reference Liu S, Qiao X, Ji C, et al (2021) Gastric poorly cohesive carcinoma: differentiation from tubular adenocarcinoma using nomograms based on CT findings in the 40 s late arterial phase. European Radiology 31:5768-5778.CrossRefPubMed Liu S, Qiao X, Ji C, et al (2021) Gastric poorly cohesive carcinoma: differentiation from tubular adenocarcinoma using nomograms based on CT findings in the 40 s late arterial phase. European Radiology 31:5768-5778.CrossRefPubMed
19.
go back to reference Xu M, Liu S, Qiao X, Li L, Ji C, Zhou Z (2022) Clinicopathological features and CT findings of papillary gastric adenocarcinoma. Abdominal Radiology 47:3698-3711.CrossRefPubMed Xu M, Liu S, Qiao X, Li L, Ji C, Zhou Z (2022) Clinicopathological features and CT findings of papillary gastric adenocarcinoma. Abdominal Radiology 47:3698-3711.CrossRefPubMed
20.
go back to reference Sano T, Aiko T (2011) New Japanese classifications and treatment guidelines for gastric cancer: revision concepts and major revised points. Gastric Cancer 14:97-100.CrossRefPubMed Sano T, Aiko T (2011) New Japanese classifications and treatment guidelines for gastric cancer: revision concepts and major revised points. Gastric Cancer 14:97-100.CrossRefPubMed
21.
22.
go back to reference Song HJ, Srivastava A, Lee J, et al (2010) Host inflammatory response predicts survival of patients with Epstein-Barr virus-associated gastric carcinoma. Gastroenterology 139:84-92 e82 Song HJ, Srivastava A, Lee J, et al (2010) Host inflammatory response predicts survival of patients with Epstein-Barr virus-associated gastric carcinoma. Gastroenterology 139:84-92 e82
23.
go back to reference Fukayama M, Abe H, Kunita A, et al (2020) Thirty years of Epstein-Barr virus-associated gastric carcinoma. Virchows Arch 476:353-365.CrossRefPubMed Fukayama M, Abe H, Kunita A, et al (2020) Thirty years of Epstein-Barr virus-associated gastric carcinoma. Virchows Arch 476:353-365.CrossRefPubMed
24.
go back to reference Chen BJ, Chapuy B, Ouyang J, et al (2013) PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies. Clinical Cancer Research 19:3462-3473.CrossRefPubMedPubMedCentral Chen BJ, Chapuy B, Ouyang J, et al (2013) PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies. Clinical Cancer Research 19:3462-3473.CrossRefPubMedPubMedCentral
25.
go back to reference Green MR, Rodig S, Juszczynski P, et al (2012) Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res 18:1611-1618.CrossRefPubMedPubMedCentral Green MR, Rodig S, Juszczynski P, et al (2012) Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res 18:1611-1618.CrossRefPubMedPubMedCentral
26.
go back to reference Liang P, Ren XC, Gao JB, Chen KS (2019) CT findings and clinical features of Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma. Medicine (Baltimore) 98:e14839.CrossRefPubMed Liang P, Ren XC, Gao JB, Chen KS (2019) CT findings and clinical features of Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma. Medicine (Baltimore) 98:e14839.CrossRefPubMed
27.
go back to reference Maeda E, Akahane M, Uozaki H, et al (2009) CT appearance of Epstein-Barr virus-associated gastric carcinoma. Abdom Imaging 34:618-625.CrossRefPubMed Maeda E, Akahane M, Uozaki H, et al (2009) CT appearance of Epstein-Barr virus-associated gastric carcinoma. Abdom Imaging 34:618-625.CrossRefPubMed
28.
go back to reference Li J, Dong D, Fang M, et al (2020) Dual-energy CT-based deep learning radiomics can improve lymph node metastasis risk prediction for gastric cancer. Eur Radiol 30:2324-2333.CrossRefPubMed Li J, Dong D, Fang M, et al (2020) Dual-energy CT-based deep learning radiomics can improve lymph node metastasis risk prediction for gastric cancer. Eur Radiol 30:2324-2333.CrossRefPubMed
29.
go back to reference Silva AC, Morse BG, Hara AK, Paden RG, Hongo N, Pavlicek W (2011) Dual-energy (spectral) CT: applications in abdominal imaging. Radiographics 31:1031–1046; discussion 1047–1050. Silva AC, Morse BG, Hara AK, Paden RG, Hongo N, Pavlicek W (2011) Dual-energy (spectral) CT: applications in abdominal imaging. Radiographics 31:1031–1046; discussion 1047–1050.
30.
go back to reference Bouhamama A, Leporq B, Khaled W, et al (2022) Prediction of Histologic Neoadjuvant Chemotherapy Response in Osteosarcoma Using Pretherapeutic MRI Radiomics. Radiol Imaging Cancer 4:e210107.CrossRefPubMedPubMedCentral Bouhamama A, Leporq B, Khaled W, et al (2022) Prediction of Histologic Neoadjuvant Chemotherapy Response in Osteosarcoma Using Pretherapeutic MRI Radiomics. Radiol Imaging Cancer 4:e210107.CrossRefPubMedPubMedCentral
31.
go back to reference Chong HH, Yang L, Sheng RF, et al (2021) Multi-scale and multi-parametric radiomics of gadoxetate disodium-enhanced MRI predicts microvascular invasion and outcome in patients with solitary hepatocellular carcinoma </= 5 cm. Eur Radiol 31:4824-4838.CrossRefPubMedPubMedCentral Chong HH, Yang L, Sheng RF, et al (2021) Multi-scale and multi-parametric radiomics of gadoxetate disodium-enhanced MRI predicts microvascular invasion and outcome in patients with solitary hepatocellular carcinoma </= 5 cm. Eur Radiol 31:4824-4838.CrossRefPubMedPubMedCentral
Metadata
Title
Epstein–Barr virus positive gastric cancer: the pathological basis of CT findings and radiomics models prediction
Authors
Shuangshuang Sun
Lin Li
Mengying Xu
Ying Wei
Feng Shi
Song Liu
Publication date
24-04-2024
Publisher
Springer US
Published in
Abdominal Radiology
Print ISSN: 2366-004X
Electronic ISSN: 2366-0058
DOI
https://doi.org/10.1007/s00261-024-04306-8
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