Development and Validation of an Individualized Nomogram for Predicting Survival in Patients with Esophageal Carcinoma after Resection

Du, Feng; Sun, Zhiwei; Jia, Jun; Ying, Yang; Yu, Jing; Shi, Yuequan; Jia, Bo; Zhao, Jiuda; Zhang, Xiaodong

doi:10.7150/jca.40767

Cited by 29 publications

(30 citation statements)

References 17 publications

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“…*P < 0.05, **P < 0.01, ***P < 0.001. system has high specificity, stability, accuracy, and sensitivity, which makes it convenient for clinical practice (37). The use of the TNM staging, the most commonly used indicator in prognosis and treatment, is still controversial because it is based on the limited anatomical range of tumors without the consideration of any other prognostic biomarkers (38). Therefore, our study integrated TNM staging and PEDF expression to estimate the OS of ESCC patients, and the 1-, 3-, and 5-year AUC values of the nomogram indicated that it was more accurate for predicting prognosis than the TNM stage ( Figure 3C).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of PEDF Predicts a Poor Prognosis and Promotes Esophageal Squamous Cell Carcinoma Progression by Modulating the MAPK/ERK Signaling Pathway

et al. 2021

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Invasion and metastasis represent the primary causes of therapeutic failure in patients diagnosed with esophageal squamous cell carcinoma (ESCC). The lack of effective treatment strategies for metastatic ESCC is the major cause of the low survival rate. Therefore, it is crucial to understand the molecular mechanisms underlying ESCC metastasis and identify potential biomarkers for targeted therapy. Herein, we reported that PEDF is significantly correlated with tumor cell invasion and metastasis in ESCC. The high expression of PEDF is an independent unfavorable prognostic factor for ESCC patients’ overall survival (OS). We successfully developed and verified a nomogram to predict the preoperative OS of ESCC patients, and the actual and nomogram-predicted 1-, 3-, and 5-year survival rates had good consistency. The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) values for 1-, 3- and 5- survival were 0.764, 0.871, and 0.91, respectively. Overexpression of PEDF significantly promoted the migration and invasion of ESCC cells in vitro, while silencing PEDF yielded the opposite effects. Elevated levels of PEDF altered the expression of proteins involved in epithelial–mesenchymal transition (EMT), as indicated by the upregulation of N-cadherin and the downregulation of α-catenin and E-cadherin in ESCC cells. Mechanistically, PEDF promoted tumor cell motility and EMT by activating the MAPK/ERK signaling pathway. In conclusion, our results reveal that PEDF is involved in ESCC metastasis and could act as a prognostic factor for ESCC. Our research provides a fresh perspective into the mechanism of ESCC metastasis.

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Section: Discussionmentioning

confidence: 99%

Upregulation of PEDF Predicts a Poor Prognosis and Promotes Esophageal Squamous Cell Carcinoma Progression by Modulating the MAPK/ERK Signaling Pathway

et al. 2021

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“…So far, the tumor node metastasis (TNM) classi cation is the most commonly utilized tool for predicting the prognosis in cancer patients [29]. However, increasing evidences demonstrated the unsatisfactory discriminative capacity of TNM system in predicting clinical outcomes [30,31]. With the development of life science and technology, more and more prognostic markers have been identi ed for ESCA [3].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a novel prognostic index based on m6A RNA methylation regulators in esophageal carcinoma

Yang¹,

Duan²,

Zhao³

et al. 2020

Preprint

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Background The incidence and mortality rate of esophageal carcinoma (ESCA) remains high. This study proposed to explore the promising prognostic markers based on m6A RNA methylation regulators, and finally to improve the prognostic assessment for ESCA patients. Methods The RNA sequencing and relevant clinical data of ESCA and normal tissues were obtained from The Cancer Genome Atlas (TCGA) database. Then, we evaluated the expression pattern of 13 m6A methylation regulators in ESCA and normal samples. Two groups of ESCA were divided by the consensus clustering analysis. STRING database and R package were used to construct the protein-protein interaction network and conduct correlation analysis, respectively. Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop the multiple-gene risk signature. Kaplan-Meier method and receiver operating characteristic (ROC) curves were used to assess the accuracy of the model. The clinical nomogram combining clinicpathological factors and gene signature was built to predict survival rate of ESCA patients. Gene set enrichment analysis (GSEA) and networks prediction analysis were conducted to explore the signaling pathways that related to the risk genes. Results Eight m6A methylation regulators (HNRNPC, YTHDF1, METTL3, YTHDF2, WTAP, YTHDC1, KIAA1429, and RBM15) were significantly upregulated in ESCA. Two clusters of ESCA with obvious differences in tumor stage were identified via the consensus clustering analysis. A two-gene signature, ALKBH5 and HNRNPC, was established for predicting the prognosis of ESCA patients. Kaplan-Meier curves illustrated that the overall survival of patients in low-risk group was obviously longer than that of patients in high-risk group (P = 1.411e-02). Importantly, risk score and tumor stage were identified as the independent prognostic indicators. The testing dataset GSE13898 showed that the nomogram had a good capacity to assess the prognosis of ESCA patients. Cell cycle, mTOR pathway, and p53 signaling pathway were found to be related to the dysregulation of risk genes. Conclusions m6A RNA methylation regulators ALKBH5 and HNRNPC could act as prognostic indicators and therapeutic targets for prognostic analysis and cancer treatment of ESCA.

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“…computed tomography (CT) was used to rule out distant metastasis and determine the initial stage. Carcinoma in situ can be treated by endoscopic mucosal resection, while local tumors with or without regional lymph node metastasis can be treated by esophagectomy, chemotherapy, chemotherapy or combination therapy [8,9]. Unresectable tumors or tumors with distant metastases outside the region are treated with palliative interventional therapy [10].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

Yan¹,

Zhang²,

Yi³

et al. 2020

Preprint

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Background: Esophageal cancer (ESCC) is one of the most common malignant tumors in the digestive system. This study aims to explore the effects of sperm associated antigen 5 (SPAG5) on cell growth, metastasis, and azithromycin resistance in esophagus cancer and its molecular mechanism.Methods: The DEGs were obtained from GSE92396, GSE17351, and GSE9982 datasets about ESCC. The PPI network was constructed using the STRING database and was visualized using Cytoscape software. The cytohubba plug-in of Cytoscape software was used to identify the hub genes of the PPI network. The DEGs were used to perform GO and KEGG pathway enrichment analysis using the DAVID database. Statistical analysis was performed to test the clinical and prognostic significance of SPAG5. Cell viability, proliferation, apoptosis, migration, and invasion were detected using CCK-8, colony formation, flow cytometry, transwell and scratch-wound assays. The expression of related genes was detected by qRT-PCR, western blot and IHC assays. The oncogenicity of SPAG5 in ESCC cells was determined using the nude mouse transplantation tumor experiment.Results: Ninety-three overlapping genes from the DEGs were used to construct the PPI network, and mainly enriched in BP, CC, and MF terms. COX regression analysis of OS showed that SPAG5 expression and pN category were correlated with OS. Univariate and multivariate analyses showed that SPAG5 was an independent prognostic factor for OS in ESCC. The ROC curve analysis showed the AUC of SPAG5 was 0.74. Multiple logistic regression showed that SPAG5 were subsequently identified as an independent risk factor associated with OS. SPAG5 overexpression was detected in ESCC tissues and cell lines, and improved cell proliferation. SPAG5 knockdown reduced cell growth and metastasis and promoted its apoptosis. The functions of SPAG5 overexpression promoting ESCC cell growth and affecting cleaved caspase-3, Ki67, VEGF, and MMP-2/-9 expression were reversed by PI3K/AKT inhibitor. SPAG5 overexpression enhanced resistance to ADM in EC9706 and Eca109 cells and it was closely related to the activation of PI3K/AKT signaling pathway.Conclusion: The overexpression of SPAG5 was an independent good prognostic factor and promoted the proliferation, invasion, migration, and ADM resistance, and inhibited the apoptosis via activating PI3K/AKT signaling pathway in ESCC.

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Development and Validation of an Individualized Nomogram for Predicting Survival in Patients with Esophageal Carcinoma after Resection

Cited by 29 publications

References 17 publications

Upregulation of PEDF Predicts a Poor Prognosis and Promotes Esophageal Squamous Cell Carcinoma Progression by Modulating the MAPK/ERK Signaling Pathway

Upregulation of PEDF Predicts a Poor Prognosis and Promotes Esophageal Squamous Cell Carcinoma Progression by Modulating the MAPK/ERK Signaling Pathway

Identification and validation of a novel prognostic index based on m6A RNA methylation regulators in esophageal carcinoma

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

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