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1.
Dig Liver Dis ; 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38246825

RESUMEN

BACKGROUND AND AIMS: The diagnosis and stratification of gastric atrophy (GA) predict patients' gastric cancer progression risk and determine endoscopy surveillance interval. We aimed to construct an artificial intelligence (AI) system for GA endoscopic identification and risk stratification based on the Kimura-Takemoto classification. METHODS: We constructed the system using two trained models and verified its performance. First, we retrospectively collected 869 images and 119 videos to compare its performance with that of endoscopists in identifying GA. Then, we included original image cases of 102 patients to validate the system for stratifying GA and comparing it with endoscopists with different experiences. RESULTS: The sensitivity of model 1 was higher than that of endoscopists (92.72% vs. 76.85 %) at image level and also higher than that of experts (94.87% vs. 85.90 %) at video level. The system outperformed experts in stratifying GA (overall accuracy: 81.37 %, 73.04 %, p = 0.045). The accuracy of this system in classifying non-GA, mild GA, moderate GA, and severe GA was 80.00 %, 77.42 %, 83.33 %, and 85.71 %, comparable to that of experts and better than that of seniors and novices. CONCLUSIONS: We established an expert-level system for GA endoscopic identification and risk stratification. It has great potential for endoscopic assessment and surveillance determinations.

3.
NPJ Digit Med ; 6(1): 64, 2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37045949

RESUMEN

White light endoscopy is the most pivotal tool for detecting early gastric neoplasms. Previous artificial intelligence (AI) systems were primarily unexplainable, affecting their clinical credibility and acceptability. We aimed to develop an explainable AI named ENDOANGEL-ED (explainable diagnosis) to solve this problem. A total of 4482 images and 296 videos with focal lesions from 3279 patients from eight hospitals were used for training, validating, and testing ENDOANGEL-ED. A traditional sole deep learning (DL) model was trained using the same dataset. The performance of ENDOANGEL-ED and sole DL was evaluated on six levels: internal and external images, internal and external videos, consecutive videos, and man-machine comparison with 77 endoscopists in videos. Furthermore, a multi-reader, multi-case study was conducted to evaluate the ENDOANGEL-ED's effectiveness. A scale was used to compare the overall acceptance of endoscopists to traditional and explainable AI systems. The ENDOANGEL-ED showed high performance in the image and video tests. In man-machine comparison, the accuracy of ENDOANGEL-ED was significantly higher than that of all endoscopists in internal (81.10% vs. 70.61%, p < 0.001) and external videos (88.24% vs. 78.49%, p < 0.001). With ENDOANGEL-ED's assistance, the accuracy of endoscopists significantly improved (70.61% vs. 79.63%, p < 0.001). Compared with the traditional AI, the explainable AI increased the endoscopists' trust and acceptance (4.42 vs. 3.74, p < 0.001; 4.52 vs. 4.00, p < 0.001). In conclusion, we developed a real-time explainable AI that showed high performance, higher clinical credibility, and acceptance than traditional DL models and greatly improved the diagnostic ability of endoscopists.

4.
Therap Adv Gastroenterol ; 16: 17562848231155023, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36895279

RESUMEN

Background: Changes in gastric mucosa caused by Helicobacter pylori (H. pylori) infection affect the observation of early gastric cancer under endoscopy. Although previous researches reported that computer-aided diagnosis (CAD) systems have great potential in the diagnosis of H. pylori infection, their explainability remains a challenge. Objective: We aim to develop an explainable artificial intelligence system for diagnosing H. pylori infection (EADHI) and giving diagnostic basis under endoscopy. Design: A case-control study. Methods: We retrospectively obtained 47,239 images from 1826 patients between 1 June 2020 and 31 July 2021 at Renmin Hospital of Wuhan University for the development of EADHI. EADHI was developed based on feature extraction combining ResNet-50 and long short-term memory networks. Nine endoscopic features were used for H. pylori infection. EADHI's performance was evaluated and compared to that of endoscopists. An external test was conducted in Wenzhou Central Hospital to evaluate its robustness. A gradient-boosting decision tree model was used to examine the contributions of different mucosal features for diagnosing H. pylori infection. Results: The system extracted mucosal features for diagnosing H. pylori infection with an overall accuracy of 78.3% [95% confidence interval (CI): 76.2-80.3]. The accuracy of EADHI for diagnosing H. pylori infection (91.1%, 95% CI: 85.7-94.6) was significantly higher than that of endoscopists (by 15.5%, 95% CI: 9.7-21.3) in internal test. And it showed a good accuracy of 91.9% (95% CI: 85.6-95.7) in external test. Mucosal edema was the most important diagnostic feature for H. pylori positive, while regular arrangement of collecting venules was the most important H. pylori negative feature. Conclusion: The EADHI discerns H. pylori gastritis with high accuracy and good explainability, which may improve the trust and acceptability of endoscopists on CADs. Plain language summary: An explainable AI system for Helicobacter pylori with good diagnostic performance Helicobacter pylori (H. pylori) is the main risk factor for gastric cancer (GC), and changes in gastric mucosa caused by H. pylori infection affect the observation of early GC under endoscopy. Therefore, it is necessary to identify H. pylori infection under endoscopy. Although previous research showed that computer-aided diagnosis (CAD) systems have great potential in H. pylori infection diagnosis, their generalization and explainability are still a challenge. Herein, we constructed an explainable artificial intelligence system for diagnosing H. pylori infection (EADHI) using images by case. In this study, we integrated ResNet-50 and long short-term memory (LSTM) networks into the system. Among them, ResNet50 is used for feature extraction, LSTM is used to classify H. pylori infection status based on these features. Furthermore, we added the information of mucosal features in each case when training the system so that EADHI could identify and output which mucosal features are contained in a case. In our study, EADHI achieved good diagnostic performance with an accuracy of 91.1% [95% confidence interval (CI): 85.7-94.6], which was significantly higher than that of endoscopists (by 15.5%, 95% CI: 9.7-21.3%) in internal test. In addition, it showed a good diagnostic accuracy of 91.9% (95% CI: 85.6-95.7) in external tests. The EADHI discerns H. pylori gastritis with high accuracy and good explainability, which may improve the trust and acceptability of endoscopists on CADs. However, we only used data from a single center to develop EADHI, and it was not effective in identifying past H. pylori infection. Future, multicenter, prospective studies are needed to demonstrate the clinical applicability of CADs.

5.
Gastrointest Endosc ; 98(2): 181-190.e10, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36849056

RESUMEN

BACKGROUND AND AIMS: EGD is essential for GI disorders, and reports are pivotal to facilitating postprocedure diagnosis and treatment. Manual report generation lacks sufficient quality and is labor intensive. We reported and validated an artificial intelligence-based endoscopy automatic reporting system (AI-EARS). METHODS: The AI-EARS was designed for automatic report generation, including real-time image capturing, diagnosis, and textual description. It was developed using multicenter datasets from 8 hospitals in China, including 252,111 images for training, 62,706 images, and 950 videos for testing. Twelve endoscopists and 44 endoscopy procedures were consecutively enrolled to evaluate the effect of the AI-EARS in a multireader, multicase, crossover study. The precision and completeness of the reports were compared between endoscopists using the AI-EARS and conventional reporting systems. RESULTS: In video validation, the AI-EARS achieved completeness of 98.59% and 99.69% for esophageal and gastric abnormality records, respectively, accuracies of 87.99% and 88.85% for esophageal and gastric lesion location records, and 73.14% and 85.24% for diagnosis. Compared with the conventional reporting systems, the AI-EARS achieved greater completeness (79.03% vs 51.86%, P < .001) and accuracy (64.47% vs 42.81%, P < .001) of the textual description and completeness of the photo-documents of landmarks (92.23% vs 73.69%, P < .001). The mean reporting time for an individual lesion was significantly reduced (80.13 ± 16.12 seconds vs 46.47 ± 11.68 seconds, P < .001) after the AI-EARS assistance. CONCLUSIONS: The AI-EARS showed its efficacy in improving the accuracy and completeness of EGD reports. It might facilitate the generation of complete endoscopy reports and postendoscopy patient management. (Clinical trial registration number: NCT05479253.).


Asunto(s)
Inteligencia Artificial , Aprendizaje Profundo , Humanos , Estudios Cruzados , China , Hospitales
6.
Endoscopy ; 55(7): 636-642, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36623838

RESUMEN

BACKGROUND: Qualified reprocessing, of which meticulous channel brushing is the most crucial step, is essential for prevention and control of endoscopy-associated infections. However, channel brushing is often omitted in practice. This study aimed to evaluate the effect of an automated flexible endoscope channel brushing system (AECBS) on improving the quality of endoscope reprocessing. METHODS: This prospective, randomized controlled study was conducted between 24 November 2021 and 22 January 2022 at Renmin Hospital of Wuhan University, China. Eligible endoscopes were randomly allocated to the auto group (channels brushed by AECBS) or the manual group (channels brushed manually), with sampling and culturing after high-level disinfection and drying. The primary end point was the proportion of endoscopes with positive cultures. RESULTS: 204 endoscopes in the auto group and 205 in the manual group were analyzed. The proportion of endoscopes with positive cultures was significantly lower in the auto group (15.2 % [95 %CI 10.7 %-21.0 %]) than in the manual group (23.4 % [95 %CI 17.9 %-29.9 %]). CONCLUSIONS: AECBS could effectively reduce bioburden and improve reprocessing quality of gastroscopes and colonoscopes. AECBS has the potential to replace manual brushing and lower the risk of endoscopy-associated infections, providing a new option for the optimization of reprocessing.


Asunto(s)
Colonoscopios , Endoscopios , Humanos , Estudios Prospectivos , Gastroscopios , Desinfección , Contaminación de Equipos/prevención & control
8.
EClinicalMedicine ; 46: 101366, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35521066

RESUMEN

Background: Prompt diagnosis of early gastric cancer (EGC) is crucial for improving patient survival. However, most previous computer-aided-diagnosis (CAD) systems did not concretize or explain diagnostic theories. We aimed to develop a logical anthropomorphic artificial intelligence (AI) diagnostic system named ENDOANGEL-LA (logical anthropomorphic) for EGCs under magnifying image enhanced endoscopy (M-IEE). Methods: We retrospectively collected data for 692 patients and 1897 images from Renmin Hospital of Wuhan University, Wuhan, China between Nov 15, 2016 and May 7, 2019. The images were randomly assigned to the training set and test set by patient with a ratio of about 4:1. ENDOANGEL-LA was developed based on feature extraction combining quantitative analysis, deep learning (DL), and machine learning (ML). 11 diagnostic feature indexes were integrated into seven ML models, and an optimal model was selected. The performance of ENDOANGEL-LA was evaluated and compared with endoscopists and sole DL models. The satisfaction of endoscopists on ENDOANGEL-LA and sole DL model was also compared. Findings: Random forest showed the best performance, and demarcation line and microstructures density were the most important feature indexes. The accuracy of ENDOANGEL-LA in images (88.76%) was significantly higher than that of sole DL model (82.77%, p = 0.034) and the novices (71.63%, p<0.001), and comparable to that of the experts (88.95%). The accuracy of ENDOANGEL-LA in videos (87.00%) was significantly higher than that of the sole DL model (68.00%, p<0.001), and comparable to that of the endoscopists (89.00%). The accuracy (87.45%, p<0.001) of novices with the assistance of ENDOANGEL-LA was significantly improved. The satisfaction of endoscopists on ENDOANGEL-LA was significantly higher than that of sole DL model. Interpretation: We established a logical anthropomorphic system (ENDOANGEL-LA) that can diagnose EGC under M-IEE with diagnostic theory concretization, high accuracy, and good explainability. It has the potential to increase interactivity between endoscopists and CADs, and improve trust and acceptability of endoscopists for CADs. Funding: This work was partly supported by a grant from the Hubei Province Major Science and Technology Innovation Project (2018-916-000-008) and the Fundamental Research Funds for the Central Universities (2042021kf0084).

9.
Endoscopy ; 54(8): 771-777, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35272381

RESUMEN

BACKGROUND AND STUDY AIMS: Endoscopic reports are essential for the diagnosis and follow-up of gastrointestinal diseases. This study aimed to construct an intelligent system for automatic photo documentation during esophagogastroduodenoscopy (EGD) and test its utility in clinical practice. PATIENTS AND METHODS: Seven convolutional neural networks trained and tested using 210,198 images were integrated to construct the endoscopic automatic image reporting system (EAIRS). We tested its performance through man-machine comparison at three levels: internal, external, and prospective test. Between May 2021 and June 2021, patients undergoing EGD at Renmin Hospital of Wuhan University were recruited. The primary outcomes were accuracy for capturing anatomical landmarks, completeness for capturing anatomical landmarks, and detected lesions. RESULTS: The EAIRS outperformed endoscopists in retrospective internal and external test. A total of 161 consecutive patients were enrolled in the prospective test. The EAIRS achieved an accuracy of 95.2% in capturing anatomical landmarks in the prospective test. It also achieved higher completeness on capturing anatomical landmarks compared with endoscopists: (93.1% vs. 88.8%), and was comparable to endoscopists on capturing detected lesions: (99.0% vs. 98.0%). CONCLUSIONS: The EAIRS can generate qualified image reports and could be a powerful tool for generating endoscopic reports in clinical practice.


Asunto(s)
Aprendizaje Profundo , Endoscopía del Sistema Digestivo , Endoscopía/métodos , Endoscopía del Sistema Digestivo/métodos , Humanos , Estudios Prospectivos
10.
Gastrointest Endosc ; 95(1): 92-104.e3, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34245752

RESUMEN

BACKGROUND AND AIMS: We aimed to develop and validate a deep learning-based system that covers various aspects of early gastric cancer (EGC) diagnosis, including detecting gastric neoplasm, identifying EGC, and predicting EGC invasion depth and differentiation status. Herein, we provide a state-of-the-art comparison of the system with endoscopists using real-time videos in a nationwide human-machine competition. METHODS: This multicenter, prospective, real-time, competitive comparative, diagnostic study enrolled consecutive patients who received magnifying narrow-band imaging endoscopy at the Peking University Cancer Hospital from June 9, 2020 to November 17, 2020. The offline competition was conducted in Wuhan, China, and the endoscopists and the system simultaneously read patients' videos and made diagnoses. The primary outcomes were sensitivity in detecting neoplasms and diagnosing EGCs. RESULTS: One hundred videos, including 37 EGCs and 63 noncancerous lesions, were enrolled; 46 endoscopists from 44 hospitals in 19 provinces in China participated in the competition. The sensitivity rates of the system for detecting neoplasms and diagnosing EGCs were 87.81% and 100%, respectively, significantly higher than those of endoscopists (83.51% [95% confidence interval [CI], 81.23-85.79] and 87.13% [95% CI, 83.75-90.51], respectively). Accuracy rates of the system for predicting EGC invasion depth and differentiation status were 78.57% and 71.43%, respectively, slightly higher than those of endoscopists (63.75% [95% CI, 61.12-66.39] and 64.41% [95% CI, 60.65-68.16], respectively). CONCLUSIONS: The system outperformed endoscopists in identifying EGCs and was comparable with endoscopists in predicting EGC invasion depth and differentiation status in videos. This deep learning-based system could be a powerful tool to assist endoscopists in EGC diagnosis in clinical practice.


Asunto(s)
Aprendizaje Profundo , Neoplasias Gástricas , Endoscopía Gastrointestinal , Humanos , Imagen de Banda Estrecha , Estudios Prospectivos , Neoplasias Gástricas/diagnóstico por imagen
11.
Front Med (Lausanne) ; 8: 781256, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34970565

RESUMEN

Background and Aims: To investigate the impact of the computer-assisted system on esophagogastroduodenoscopy (EGD) training for novice trainees in a prospective randomized controlled trial. Methods: We have constructed a computer-aided system (CAD) using retrospective images based on deep learning which could automatically monitor the 26 anatomical landmarks of the upper digestive tract and document standard photos. Six novice trainees were allocated and grouped into the CAD group and control group. Each of them took the training course, pre and post-test, and EGD examination scored by two experts. The CAD group was trained with the assistance of the CAD system and the control group without. Results: Both groups achieved great improvements in EGD skills. The CAD group received a higher examination grading score in the EGD examination (72.83 ± 16.12 vs. 67.26 ± 15.64, p = 0.039), especially in the mucosa observation (26.40 ± 6.13 vs. 24.11 ± 6.21, p = 0.020) and quality of collected images (7.29 ± 1.09 vs. 6.70 ± 1.05). The CAD showed a lower blind spot rate (2.19 ± 2.28 vs. 3.92 ± 3.30, p = 0.008) compared with the control group. Conclusion: The artificial intelligence assistant system displayed assistant capacity on standard EGD training, and assisted trainees in achieving a learning curve with high operation quality, which has great potential for application. Clinical Trial Registration: This trial is registered at https:/clinicaltrials.gov/, number NCT04682821.

12.
Mol Ther Nucleic Acids ; 25: 567-577, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34589278

RESUMEN

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. MicroRNAs (miRNAs) are known to be important regulators of GC. This study aims to investigate the role of miRNA (miR)-497 in GC. We demonstrated that the expression of miR-497 was downregulated in human GC tissues. After N-methyl-N-nitrosourea treatment, the incidence of GC in miR-497 knockout mice was significantly higher than that in wild-type mice. miR-497 overexpression suppressed GC cell proliferation, cell-cycle progression, colony formation, anti-apoptosis ability, and cell migration and invasion capacity. Additionally, miR-497 overexpression decreased the expression levels of cell division cycle 42 (CDC42) and integrin ß1 (ITGB1) and inhibited the phosphorylation of focal adhesion kinase (FAK), paxillin (PXN), and serine-threonine protein kinase (AKT). Furthermore, overexpression of miR-497 inhibited the metastasis of GC cells in vivo, which could be counteracted by CDC42 restoration. Furthermore, the focal adhesion of GC cells was found to be regulated by miR-497/CDC42 axis via ITGB1/FAK/PXN/AKT signaling. Collectively, it is concluded that miR-497 plays an important role in the repression of GC tumorigenesis and progression, partly via the CDC42/ITGB1/FAK/PXN/AKT pathway.

13.
Lancet Gastroenterol Hepatol ; 6(9): 700-708, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34297944

RESUMEN

BACKGROUND: White light endoscopy is a pivotal first-line tool for the detection of gastric neoplasms. However, gastric neoplasms can be missed during upper gastrointestinal endoscopy due to the subtle nature of these lesions and varying skill among endoscopists. Here, we aimed to evaluate the effect of an artificial intelligence (AI) system designed to detect focal lesions and diagnose gastric neoplasms on reducing the miss rate of gastric neoplasms in clinical practice. METHODS: This single-centre, randomised controlled, tandem trial was done at Renmin Hospital of Wuhan University, China. We recruited consecutive patients (≥18 years old) undergoing routine upper gastrointestinal endoscopy for screening, surveillance, or investigation of symptoms. Same-day tandem upper gastrointestinal endoscopy was done where patients first underwent either AI-assisted (AI-first) or routine (routine-first) white light endoscopy, followed immediately by the other procedure, with targeted biopsies for all detected lesions taken at the end of the second examination. Patients were randomly assigned (1:1) to the AI-first or routine-first group using a computer-generated random numerical series and block randomisation (block size of four). Endoscopists were not blinded to randomisation status, whereas patients and pathologists were. The primary endpoint was the miss rate of gastric neoplasms and the analysis was done per protocol. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR2000034453, and has been completed. FINDINGS: Between July 6, 2020, and Dec 11, 2020, 907 patients were randomly assigned to the AI-first group and 905 to the routine-first group. The gastric neoplasm miss rate was significantly lower in the AI-first group than in the routine-first group (6·1%, 95% CI 1·6-17·9 [3/49] vs 27·3%, 15·5-43·0 [12/44]; relative risk 0·224, 95% CI 0·068-0·744; p=0·015). The only reported adverse event was bleeding from a target lesion after biopsy. INTERPRETATION: The use of an AI system during upper gastrointestinal endoscopy significantly reduced the gastric neoplasm miss rate. AI-assisted endoscopy has the potential to improve the yield of gastric neoplasms by endoscopists. FUNDING: The Project of Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision and the Hubei Province Major Science and Technology Innovation Project.


Asunto(s)
Inteligencia Artificial , Aprendizaje Profundo , Endoscopía del Sistema Digestivo/métodos , Tamizaje Masivo/métodos , Neoplasias Gástricas/diagnóstico , Adulto , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Gástricas/epidemiología
14.
Gastric Cancer ; 24(6): 1242-1253, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34076786

RESUMEN

OBJECTIVE: Eradication of Helicobacter pylori (H. pylori) could not completely prevent the progression of gastric cancer (GC), suggesting that non-H. pylori bacteria may participate in the carcinogenesis of GC. The dysbiosis of microbiota in the stomach of GC has gradually been investigated, while the detailed mechanism that promotes GC in this process has not been elucidated. We aimed to identify a non-H. pylori bacteria that contribute to GC. DESIGN: GC tissues and adjacent normal tissues were collected to identify bacteria that significantly increased in GC tissues by 16S rRNA gene sequencing and fluorescence in situ hybridization (FISH) analysis. CCK8, wound healing assay, and trans-well assay were performed to analyze the tumor-promoting effect of this bacteria. Next, we detailed the mechanism for tumor-promoting effect of the bacteria by immunofluorescence, RT-qPCR, and western-blotting analysis. RESULTS: Comparing the microbial community from GC tissues and adjacent normal tissues, we found that Propionibacterium acnes (P. acnes) significantly increased in GC tissues, especially in H. pylori-negative tissues. We further found that the abundance of P. acnes correlated with TNM stages of GC patients. Interestingly, condition medium (CM) from P. acnes-primed macrophages promoted migration of GC cells, while P. acnes only could not. We next proved that P. acnes triggers M2 polarization of macrophages via TLR4/PI3K/Akt signaling. CONCLUSIONS: Together, our finding identified that P. acnes could be a possible agent for the progression of GC besides H. pylori. M2 polarization of macrophages could be promoted by P. acnes via TLR4/PI3K/Akt signaling, thus triggers the progression of GC.


Asunto(s)
Macrófagos/metabolismo , Propionibacterium acnes/metabolismo , Neoplasias Gástricas/microbiología , Disbiosis , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Receptor Toll-Like 4/metabolismo
15.
J Exp Clin Cancer Res ; 39(1): 251, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33222684

RESUMEN

BACKGROUND: Wingless and Int-related protein (Wnt) ligands are aberrantly expressed in patients with colorectal cancer (CRC). However, the aberrant level of Wnt ligands in serum have not been explored. Here, we aimed to identify the levels of WNT4 in serum and explored its oncogenic role in CRC. METHODS: The Oncomine database was used to analyze the relationship between WNT4 and the prognosis of CRC. ELISA was performed to measure WNT4 levels in serum and conditioned medium from fresh CRC tissues and adjacent normal tissues. Western blot and immunohistochemistry were carried out to measure the expression of WNT4 in human CRC tissues and adjacent normal tissues. The migration and invasion of CRC cells were determined by trans-well assay, and the effects of WNT4 on CRC invasion and metastasis in vivo were verified by tumor xenograft in nude mice. Cancer-associated fibroblasts (CAFs) and angiogenesis in subcutaneous nodules were detected by immunofluorescence (IF). In addition, the suspended spheres formation and tube formation assay were performed to explore the effects of WNT4 on CAFs and angiogenesis respectively. RESULTS: WNT4 was significantly upregulated in serum of CRC patients, and CRC tissues were identified as an important source of elevated WNT4 levels in CRC patients. Interestingly, elevated levels of WNT4 in serum were downregulated after tumor resection. Furthermore, we found that WNT4 contributed to epithelial-to-mesenchymal transition (EMT) and activated fibroblasts by activating the WNT4/ß-catenin pathway in vitro and in vivo. Moreover, angiogenesis was induced via the WNT4/ß-catenin/Ang2 pathway. Those effects could be reversed by ICG-001, a ß-catenin/TCF inhibitor. CONCLUSION: Our findings indicated that serum levels of WNT4 may be a potential biomarker for CRC. WNT4 secreted by colorectal cancer tissues promote the progression of CRC by inducing EMT, activate fibroblasts and promote angiogenesis through the canonical Wnt/ß-catenin signalling pathway.


Asunto(s)
Neoplasias Colorrectales/sangre , Vía de Señalización Wnt , Proteína Wnt4/sangre , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Células HCT116 , Xenoinjertos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratones , Ratones Desnudos , Transfección
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