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Introduction: Endoscopic ultrasound (EUS) may play a role in evaluating treatment response after definitive chemoradiation therapy (dCRT) for esophageal squamous cell carcinoma (ESCC). This study explored the prognostic markers of EUS with biopsies and developed two nomograms for survival prediction. Methods: A total of 821 patients newly diagnosed with ESCC between January 2015 and December 2019 were reviewed. We investigated the prognostic value of the changes in tumor imaging characteristics and histopathological markers by an interim response evaluation, including presence of stenosis, ulceration, tumor length, tumor thickness, lumen involvement, and tumor remission. Independent prognostic factors of progression-free survival (PFS) and overall survival (OS) were determined using Cox regression analysis and further selected to build two nomogram models for survival prediction. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to respectively assess its discriminatory capacity, predictive accuracy, and clinical usefulness. Results: A total of 155 patients were enrolled in this study and divided into the training (109 cases) and testing (46 cases) cohorts. Tumor length, residual tumor thickness, reduction in tumor thickness, lumen involvement, and excellent remission (ER) of spatial luminal involvement in ESCC (ER/SLI) differed significantly between responders and non-responders. For patients undergoing dCRT, tumor stage (P = 0.001, 0.002), tumor length (P = 0.013, 0.008), > 0.36 reduction in tumor thickness (P = 0.004, 0.004) and ER/SLI (P = 0.041, 0.031) were independent prognostic markers for both PFS and OS. Time-dependent ROC curves, calibration curves, and DCA indicated that the predicted survival rates of our two established nomogram models were highly accurate. Conclusion: Our nomogram showed high accuracy in predicting PFS and OS for ESCC after dCRT. External validation and complementation of other biomarkers are needed in further studies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to compare the clinical outcomes of induction chemotherapy (IC) followed by definitive concurrent chemoradiotherapy (dCCRT) versus chemoradiotherapy alone in patients with esophageal squamous cell carcinoma (ESCC) on the basis of a clinical scoring model. Methods: A retrospective review of 599 patients with ESCC treated with dCCRT at our institution from 2010 to 2019 was conducted. The patients were divided into two groups based on whether they received IC. A clinical scoring model was performed using the significant variables obtained from the multivariate analysis. The PFS and OS rates were estimated using the Kaplan–Meier method. Results: During the study period, 182 patients receiving IC followed by dCCRT and 417 dCCRT alone were identified. No significant differences in the PFS and OS rates were observed between the IC group (P=0.532) and the non-IC group (P=0.078). A clinical scoring model was constructed based on independent prognostic factors with scores ranging from 0 to 10.4. The patients were divided into high- and low-risk groups by using the median score as the cutoff value. The PFS rate of patients receiving IC was higher than that of patients treated without IC (P=0.034), while there was no improvement in the OS rate (P=0.794) in the high-risk group. No significant differences in the PFS (P=0.207) or OS (P=0.997) rate were found between the two treatment groups in the low-risk group. Conclusions: The addition of IC followed by dCCRT for patients with ESCC might be associated with better PFS rates based on a clinical scoring model but has no impact on OS rates. Further prospective studies are warranted for the validation of this model. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is the primary epithelial tumor of the lung. The lack of clinical symptoms and specific molecular diagnostic indicators during the early stages of LUAD mean that the disease may not be detected until late stages, and the 5‐year survival rate is only approximately 15%. Long non‐coding RNA ALMS1 intronic script 1 (ALMS1‐IT1) was previously reported to be correlated with the poor prognosis of head and neck squamous cell carcinoma patients. Here, we investigated whether ALMS1‐IT1 has prognostic potential for LUAD. Bioinformatics analyses were performed to examine the expression and prognostic value of ALMS1 and AVL9 (for which gene expression is positively correlated with ALMS1‐IT1 expression in LUAD) in LUAD based on TCGA and Oncomine databases. We report that ALMS1‐IT1 and AVL9 were both highly expressed in LUAD and correlated with poor outcomes in LUAD patients. Of note, the prognosis of LUAD patients with low expression of both ALMS1‐IT1 and AVL9 was superior to that of other patients. Furthermore, the proliferation, migration and invasion of LUAD cells were decreased in cells lacking ALMS1‐IT1, and this decrease could be almost completely reversed through overexpression of AVL9. Gene set enrichment analysis revealed that expression of genes related to the cell cycle pathway is closely related to both the high expression of ALMS1‐IT1 and AVL9 in LUAD. Finally, up‐regulation of ALMS1‐IT1 can activate the cyclin‐dependent kinase pathway, whereas absence of AVL9 can reverse this activation, as shown by western blotting. In summary, ALMS1‐IT1/AVL9 may promote the malignant progression of LUAD, at least in part by regulating the cyclin‐dependent kinase pathway. [ABSTRACT FROM AUTHOR]

Qingwu Du and Xiaoyue Wu contributed equally to this work. 2Distributions of tumor remission (A), tumor thickness (B) and lumen involvement (C) at baseline and during treatment between responders and non-responders Graph: Fig. [Extracted from the article]

Cluster of differentiation 147 (CD147), pituitary tumor transforming gene (PTTG) and CD44v6 are proteins involved in the epithelial‑mesenchymal transition (EMT). To investigate the prognostic value of CD147 and PTTG, and CD44v6 expression in esophageal squamous cell carcinoma (ESCC), tissue microarray specimens from 76 patients with ESCC were evaluated by immunohistochemistry staining and scored by intensity and proportion of positive areas. Expression levels of CD147, PTTG and CD44v6 were higher in tumor tissues than in matched adjacent tissues. CD147 expression was positively associated with lymph node metastasis (P=0.025) and American Joint Committee on Cancer (AJCC) system clinical grades (P=0.037). CD147 expression was positively correlated with the expression levels of PTTG (R=0.369; P=0.001) and CD44v6 (R=0.320; P=0.005). In addition, Kaplan‑Meier analysis indicated that positive expression of CD147, PTTG and CD44v6 was significantly associated with poor overall survival times (P=0.045, P=0.014 and P=0.027, respectively). Patients exhibiting CD147‑PTTG co‑expression, CD147‑CD44v6 co‑expression and CD147‑PTTG‑CD44v6 triple‑positive expression had the poorest overall survival rates. In conclusion, the expression of EMT‑associated proteins, including CD147, PTTG and CD44v6, was significantly associated with poor survival in ESCC and these novel targets may serve as potential biomarkers for anticancer therapies. [ABSTRACT FROM AUTHOR]

Aims: The asymptomatic nature of early-stage esophageal squamous cell carcinoma (ESCC) results in late presentation and consequent dismal prognosis This study characterized 14-3-3σ protein expression in the multi-stage development of ESCC and determined its correlation with clinical features and prognosis. Materials and Methods: Western blot was used to examine 14-3-3σ protein expression in normal esophageal epithelium (NEE), low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), ESCC of TNM I to IV stage and various esophageal epithelial cell lines with different biological behavior. Immunohistochemistry was used to estimate 14-3-3σ protein in 110 biopsy samples of NEE, LGIN or HGIN and in 168 ESCC samples all of whom had follow-up data. Support vector machine (SVM) was used to develop a classifier for prognosis. Results: 14-3-3σ decreased progressively from NEE to LGIN, to HGIN, and to ESCC. Chemoresistant sub-lines of EC9706/PTX and EC9706/CDDP showed high expression of 14-3-3σ protein compared with non-chemoresistant ESCC cell lines and immortalized NEC. Furthermore, the downregulation of 14-3-3σ correlated significantly with histological grade (P = 0.000) and worse prognosis (P = 0.004). Multivariate Cox regression analysis indicated that 14-3-3σ protein (P = 0.016) and T stage (P = 0.000) were independent prognostic factors for ESCC. The SVM ESCC classifier comprising sex, age, T stage, histological grade, lymph node metastasis, clinical stage and 14-3-3σ, distinguished significantly lower- and higher-risk ESCC patients (91.67% vs. 3.62%, P = 0.000). Conclusions: Downregulation of 14-3-3σ arises early in the development of ESCC and predicts poor survival, suggesting that 14-3-3σ may be a biomarker for early detection of high-risk subjects and diagnosis of ESCC. Our seven-feature SVM classifier for ESCC prognosis may help to inform clinical decisions and tailor individual therapy. [ABSTRACT FROM AUTHOR]