We analyzed data from two non-coding RNA profiling arrays made available by the Gene Expression Omnibus (GEO) and found 17 miRNAs with remarkable differential expression between malignant and normal esophageal tissue. Correlation analysis between expression of these 17 miRNAs and patients' clinicopathological characteristics showed that miR-203 was down-regulated in esophageal carcinoma (EC) tissues and was significantly associated with lymph node metastasis and poor overall survival. Overexpression of miR-203 significantly attenuated cellular proliferation, migration and invasion by EC cells in culture. Additionally, gene expression profiles and bioinformatics analysis revealed KIF5C to be a direct target of miR-203, and KIF5C overexpression partially counteracted the tumor inhibitory effects of miR-203 on EC cells. We also observed that miR-203, reduced KIFC5 protein levels, promoted cytoplasmic accumulation of Axin2, and reversed the invasive phenotype of EC cells. Taken together, these data demonstrate that miR-203 is a tumor suppressor in EC cells and its expression level could potentially be used as a prognostic indicator for EC patient outcomes.

Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the digestive tract with complex pathogenesis. There is a pressing need to search for ESCC targeted therapy sites and explore its pathogenesis. Prothymosin alpha (PTMA) is abnormally expressed in numerous tumors and has a significant regulatory effect on tumor malignant progression. However, the regulatory role and mechanism of PTMA in ESCC have not yet been reported. Methods: We first detected the PTMA expression in ESCC patients, subcutaneous tumor xenograft models of ESCC, and ESCC cells. Subsequently, PTMA expression in ESCC cells was inhibited by cell transfection, and cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, and Western blot. A dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was used to detect reactive oxygen species (ROS) level in cells, and MitoSOX fluorescent probe, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining, mitochondrial complex kit, and Western blot were used to detect the expression of mitochondrial oxidative phosphorylation. Next, the combination between PTMA and high mobility group box 1 (HMGB1) was detected using Co-immunoprecipitation (co-IP) and immunofluorescence (IF) techniques. Finally, the expression of PTMA was inhibited and the expression of HMGB1 was overexpressed in cells via cell transfection, and the regulatory effect of PTMA and HMGB1 binding on mitochondrial oxidative phosphorylation in ESCC was determined through related experiments. Results: The expression of PTMA in ESCC was abnormally elevated. The inhibition of PTMA expression in ESCC cells significantly decreased the activity of ESCC cells and increased their apoptosis. Moreover, interference with PTMA can induce ROS aggregation in ESCC cells by inhibiting mitochondrial oxidative phosphorylation, which may be achieved by binding to HMGB1. Conclusions: PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation, thereby affecting the malignant progression of ESCC.

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e16023 Background: Camrelizumab, a programmed death 1 (PD-1) inhibitor, has recently demonstrated efficacy for esophageal squamous cell carcinoma (ESCC) patients in a phase III trial. We report real-world clinical outcomes of camrelizumab therapy for ESCC patients in a multicenter prospective cohort. Methods: Eligible patientswereadvanced esophageal squamous cell carcinoma with stage II-IV confirmed by pathology (including histology or cytology). All patients had received at most one systematic treatment and ECOG performance status of 0 or 1. Camrelizumab monotherapy(200mg) or combined with chemo-radiotherapy, chemotherapy, chemotherapy and antiangiogenic therapy as a first or second line of therapy were included. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and overall survival (OS) and safety data were evaluated. This abstract summarizes the findings of an exploratory interim analysis (cut-off Dec 2020). Results: From Oct 2019-Dec 2020, 63 patients were enrolled (19 centers in China; mean age 62.26 years; 97% ECOG PS 1; 54% first line therapy). Patients received camrelizumab monotherapy (8; 13%), camrelizumab/chemo-radiotherapy combination therapy (22, 35%), camrelizumab/chemotherapy combination therapy (26, 41%), camrelizumab/chemotherapy/antiangiogenic therapy combination therapy (7, 11%). One patient achieved a complete response and 27 patients achieved a partial response, leading to an ORR of 41.26%. The DCR was 95.24%. The median progression-free survival (PFS) was 6.33 months (95% confidence interval [CI] 4.73-NA). Among patients with adequate samples test for LBH level and (lung immune prognostic index) LIPI score, 15.7% (8/51) patients had a high LBH level;63% (29/46), 32.6% (15/46) and 4.3% (2/46) patients had a good, middle and poor LIPI score, respectively. A significantly longer PFS was observed in patients with a normal LBH level (NA vs. 6.33 months, P = 0.049), and also in patients treated with first-line therapy (6.33 months vs. NA, P = 0.0338). Among adverse events, 4 patients (6.35%) reported grade 3-4 AEs, including pneumonia (n=2 [3.17%]), and bone marrow suppression (n=2 [3.17%]). 10 of 63 patients (15.87%) experienced any grade pneumonia, and 21 of 63 patients (33.33%) experienced grade 1-2 RCCEP. Conclusions: This real-world population showed that camrelizumab as the first- or second-line therapy was an effective and safe treatment for patients with ESCC. Clinical trial information: CHICTR2000039499.