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Background: Circular RNAs (circRNAs) are well-known regulators of cancer progression and chemoresistance in various types of cancers. This study was performed to investigate the function of hsa_circ_0000277 in esophageal squamous cell carcinoma (ESCC).Methods: RNA levels were analyzed via the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8) assay was applied to determine cell proliferation and half maximal inhibitory concentration (IC50) of cisplatin (DDP). Colony formation ability was evaluated by colony formation assay. Cell cycle and apoptosis were measured using flow cytometry. RNA immunoprecipitation (RIP), pull-down assay and dual-luciferase reporter assays were performed for target interaction analysis. The protein levels were determined through western blot. Xenograft models were established for researching hsa_circ_0000277 function in vivo.Results: Hsa_circ_0000277 expression was increased in ESCC cells and tissues, and it had important clinical significance. Downregulation of hsa_circ_0000277 repressed ESCC cell proliferation, colony formation, cell cycle, and DDP resistance. Hsa_circ_0000277 acted as a microRNA-873-5p (miR-873-5p) sponge and Sry-related high-mobility group box 4 (SOX4) was validated as a target of miR-873-5p. Moreover, hsa_circ_0000277/miR-873-5p axis and miR-873-5p/SOX4 axis regulated ESCC cell progression and DDP resistance. Hsa_circ_0000277/miR-873-5p axis activated SOX4/Wnt/β-catenin signaling pathway. Hsa_circ_0000277 facilitated tumorigenesis and DDP resistance by miR-873-5p/SOX4 axis in vivo.Conclusion: These findings unraveled that hsa_circ_0000277 promoted ESCC progression and DDP resistance via miR-873-5p/SOX4/Wnt/β-catenin axis, showing a specific molecular mechanism of carcinogenesis and chemoresistance in ESCC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the feasibility of nab‐paclitaxel plus platinum‐based chemotherapy (nabTP) versus paclitaxel plus platinum‐based chemotherapy (TP) with immune checkpoint inhibitors (ICIs) as a neoadjuvant modality for locally resectable esophageal squamous cell carcinoma (ESCC). Methods: Between April 2019 and March 2022, we identified ESCC patients who received neoadjuvant immunotherapy with both nabTP (n = 213) and TP (n = 98) at our institution and Henan Cancer Hospital. The patients in the ICIs‐nabTP and ICIs‐TP groups were pair‐matched (1:1) for tumor location, sex, smoking, drinking, clinical T and N stage. The primary endpoint was the hazard of 30‐day major postoperative complications. Second, logistic models were applied to estimate the risk factors for pathological complete response (pCR) rate. Results: All patients underwent esophagectomy with R0 resection. A statistically significant increase in the risk of developing major pulmonary (odds ratio [OR], 1.182; 95% confidence interval [CI]: 0.530–2.635; p = 0.683), anastomotic (OR, 1.881; 95% CI: 0.607–5.830; p = 0.267), cardiac (OR, 1.000; 95% CI: 0.426–2.349; p = 1.000) complications after neoadjuvant immunotherapy plus nabTP was not observed. The median interval to surgery was 39 days in the ICIs‐nabTP group versus 44 days in the ICIs‐TP group (p = 0.119). There was no 30‐day mortality in each group. However, there was a slight difference in the 30‐day readmission rate (p = 0.043) and the incidence of hydropneumothorax (p = 0.027) between the two groups. The pCR rates of the ICIs‐nabTP and ICIs‐TP group were 36.7 and 21.4%, respectively (p = 0.018). Conclusions: It appears to be feasible to add immunotherapy to nabTP regimen for locally advanced ESCC. Compared with TP, nabTP plus ICIs can achieve a better pCR rate in ESCC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the value and efficiency of routine brain MRI or CT in the preoperative workup for patients with potentially resectable (cT1‐4aN0‐3) thoracic esophageal squamous cell cancer (ESCC). Methods: This was a prospective cross‐sectional clinical trial (ChiCTR1800020304). A total of 385 patients with potentially resectable (cT1‐4aN0‐3) thoracic ESCC diagnosed from October 2018 to August 2020 were included. Plain brain MRI or CT was performed preoperatively to detect brain metastases (BrM). The primary endpoint was BrM detected by imaging. Results: Of all 385 patients, the rate of positive brain MRI/CT findings was 1% (n = 4). BrM Patients received chemoradiotherapy, and the median OS was 6 months (95% CI: 4.303–7.697). All 381 remaining patients with initial negative brain MRI/CT diagnosis revealed no brain‐associated symptoms within 6 months. The median follow‐up for patients without BrM was 20 months (range, from 6 to 32). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of plain MRI or CT to detect BrM were all 100%. Conclusions: Preoperative plain MRI or CT is an effective method to detect BrM for potentially resectable (cT1‐4aN0‐3) thoracic ESCC. However, due to the low incidence, the value of brain MRI/CT as a routinely preoperational examination in potentially resectable esophageal squamous cell cancer is rather limited. Therefore, preoperative brain MRI/CT should not be recommended as a routine preoperative examination for ESCC. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest digestive tract cancer with poor prognosis. In our previous comprehensive genomics study, we identified that hotspot mutations in the solute carrier family 35 member E2 (SLC35E2) promoter region was significantly associated with worse prognosis in patients with ESCC. However, the biological function and molecular mechanism of SLC35E2 remains unclear. This study was to investigate the malignant function and mechanism of SLC35E2 in ESCC. Western blotting and qRT-PCR were used to assess the expression of SLC35E2 in ESCC cell lines. Luciferase assay and chromatin immunoprecipitation (ChIP) assay were used to assess the transcriptional inhibition of KLF4. Incucyte cell proliferation assay, colony formation assay and subcutaneous tumor formation in nude mice were used to assess the malignant function of SLC35E2. SLC35E2 can promote ESCC cell proliferation in vitro and in vivo. Krüppel-like factor 4 (KLF4), a transcriptional repressor in ESCC, binds to the SLC35E2 promoter and represses the expression of SLC35E2. The transcriptional suppression of KLF4 can be blocked by the mutation at −118 site of the SLC35E2 promoter. Besides, the accumulation of SLC35E2 expression contributes to the malignant phenotype of ESCC. These results indicate that SLC35E2 may be used as a biomarker for prognosis as well as a therapeutic target for patients with ESCC. [ABSTRACT FROM AUTHOR]