Meilin Qu1,2, Tao Han2, Xiaoquan Chen3, Qingqing Sun4, Qing Li5, Mingfang Zhao2. 1. School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China. 2. Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China. 3. Department of Integrated Traditional Chinese and Western Medicine, Shaanxi Provincial Cancer Hospital, Xi'an, China. 4. Three Departments of Convalescence, Lintong Rehabilitation and Recuperation Center, Lintong, China. 5. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Abstract
Background: Hepatocellular carcinoma (HCC) is one of the malignant tumors with the highest morbidity and mortality worldwide, and its prognosis remains a challenge. Actinidia chinensis Planch (ACP) root has good efficacy against HCC. This study aimed to explore the link between ACP and potential targets of HCC, and to develop a novel immune-based gene signature to predict HCC patient survival. Methods: Transcriptome data and clinical information on HCC were obtained from The Cancer Genome Atlas (TCGA; HCC: 374, normal: 50) and International Cancer Genome Consortium (ICGC) database (HCC: 243, normal: 202). Combined with the 2,483 immune-related genes from the Immport database, we used the least absolute shrinkage and selection operator (LASSO) to construct a prognostic model. Patients were divided into high-risk and low-risk groups by the median of the risk scores of the TCGA cohort. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves were used to estimate the predictability of the model in HCC prognosis, and carried out external validation based on ICGC cohort. We analyzed the correlation of this model with immune cells and immune checkpoint genes. Finally, molecular docking of these genes and the corresponding ACP components. Results: We constructed a prognostic model composed of 3 immune-related genes [epidermal growth factor (EGF), baculoviral inhibitor of apoptosis repeat-containing protein 5 (BIRC5), and secreted phosphoprotein 1 (SPP1)]. And the high-risk group had a lower overall survival (OS) rate compared to the low-risk group (TCGA cohort: P=1.761e-05, ICGC cohort: P=8.716e-04). The outcomes of the AUC of ROC of prognostic risk model to predict for 1-, 2-, and 3-year OS: TCGA cohort: 0.749, 0.710, and 0.653 and ICGC cohort: 0.698, 0.736, and 0.753. Molecular docking results showed that quercetin had good binding activities with SPP1, BIRC5, and EGF, and ursolic acid (UA) and BIRC5 also had this feature. Conclusions: Our study speculates that ACP root anti-HCC may be involved in the immune regulation of the body by targeting EGF, BIRC5 and SPP1, which possess great potential and value as early warning molecules for HCC. This model may provide a reference for individualized diagnosis and treatment for HCC patients. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Background: Hepatocellular carcinoma (HCC) is one of the malignant tumors with the highest morbidity and mortality worldwide, and its prognosis remains a challenge. Actinidia chinensis Planch (ACP) root has good efficacy against HCC. This study aimed to explore the link between ACP and potential targets of HCC, and to develop a novel immune-based gene signature to predict HCC patient survival. Methods: Transcriptome data and clinical information on HCC were obtained from The Cancer Genome Atlas (TCGA; HCC: 374, normal: 50) and International Cancer Genome Consortium (ICGC) database (HCC: 243, normal: 202). Combined with the 2,483 immune-related genes from the Immport database, we used the least absolute shrinkage and selection operator (LASSO) to construct a prognostic model. Patients were divided into high-risk and low-risk groups by the median of the risk scores of the TCGA cohort. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves were used to estimate the predictability of the model in HCC prognosis, and carried out external validation based on ICGC cohort. We analyzed the correlation of this model with immune cells and immune checkpoint genes. Finally, molecular docking of these genes and the corresponding ACP components. Results: We constructed a prognostic model composed of 3 immune-related genes [epidermal growth factor (EGF), baculoviral inhibitor of apoptosis repeat-containing protein 5 (BIRC5), and secreted phosphoprotein 1 (SPP1)]. And the high-risk group had a lower overall survival (OS) rate compared to the low-risk group (TCGA cohort: P=1.761e-05, ICGC cohort: P=8.716e-04). The outcomes of the AUC of ROC of prognostic risk model to predict for 1-, 2-, and 3-year OS: TCGA cohort: 0.749, 0.710, and 0.653 and ICGC cohort: 0.698, 0.736, and 0.753. Molecular docking results showed that quercetin had good binding activities with SPP1, BIRC5, and EGF, and ursolic acid (UA) and BIRC5 also had this feature. Conclusions: Our study speculates that ACP root anti-HCC may be involved in the immune regulation of the body by targeting EGF, BIRC5 and SPP1, which possess great potential and value as early warning molecules for HCC. This model may provide a reference for individualized diagnosis and treatment for HCC patients. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: Lorena González; María E Díaz; Johanna G Miquet; Ana I Sotelo; Fernando P Dominici Journal: Trends Endocrinol Metab Date: 2021-04-07 Impact factor: 12.015