The biology function of antisense intronic long noncoding RNA (Ai-lncRNA) is still unknown. Meanwhile, cancer patients with paclitaxel resistance have limited therapeutic options in the clinic. However, the potential involvement of Ai-lncRNA in paclitaxel sensitivity remains unclear in human cancer. Whole transcriptome sequencing of 33 breast specimens was performed to identify Ai-lncRNA EGOT. Next, the role of EGOT in regulation of paclitaxel sensitivity was investigated. Moreover, the mechanism of EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions was investigated in detail. Furthermore, upstream transcriptional regulation of EGOT expression was also investigated by co-immunoprecipitation and chromatin immunoprecipitation. Finally, clinical breast specimens in our cohort, TCGA and ICGC were applied to validate the role of EGOT in enhancing of paclitaxel sensitivity. EGOT enhances autophagosome accumulation via the up-regulation of ITPR1 expression, thereby sensitizing cells to paclitaxel toxicity. Mechanistically, on one hand, EGOT upregulates ITPR1 levels via formation of a pre-ITPR1/EGOT dsRNA that induces pre-ITPR1 accumulation to increase ITPR1 protein expression in cis. On the other hand, EGOT recruits hnRNPH1 to enhance the alternative splicing of pre-ITPR1 in trans via two binding motifs in EGOT segment 2 (324–645 nucleotides) in exon 1. Moreover, EGOT is transcriptionally regulated by stress conditions. Finally, EGOT expression enhances paclitaxel sensitivity via assessment of cancer specimens. These findings broaden comprehensive understanding of the biology function of Ai-lncRNAs. Proper regulation of EGOT may be a novel synergistic strategy for enhancing paclitaxel sensitivity in cancer therapy.

To uncover the mechanism of METTL3 and LncRNA DUXAP8 in esophageal squamous cell carcinoma (ESCC) progression. LncRNA DUXAP8 expression was assessed by qRT

Background: Current understanding of neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) lacks high-level evidence. This study provides additional efficacy data for this treatment regimen. Methods: Clinical trials investigating neoadjuvant tislelizumab plus chemotherapy in locally advanced ESCC were identified through literature search. Raw data from investigators were pooled for analysis. Primary endpoint was pCR; secondary endpoints included MPR, R0 resection rate, EFS, DFS, and OS. Results: Six studies involving 306 patients were analyzed; 275 (89.9%) underwent surgery. Among surgical patients, pCR rate was 25.5% and MPR rate was 49.5%. Most patients (98.5%) achieved R0 resection. At median follow-up of 31.3 months, median EFS, DFS, and OS were not reached. The 1-/2-/3-year rates were: EFS 81.8%/66.9%/59.1%; DFS 79.0%/68.7%/62.3%; and OS 91.7%/77.5%/73.4%. Tislelizumab dose intensity correlated with MPR. MPR and R0 resection were independent prognostic factors for EFS and OS, while pathological staging was associated with DFS and OS. Conclusions: Neoadjuvant tislelizumab combined with chemotherapy demonstrated promising efficacy with encouraging pathological responses and survival outcomes in locally advanced ESCC, supporting clinical application.

The definitions of regional nodes differ between the 12th edition of the JES and the UICC staging systems, and the most prominent difference is in the status of the supraclavicular lymph nodes (SCLN). This study was designed to investigate the prognostic impact of metastasis to SCLN in patients with thoracic oesophageal squamous cell carcinoma (ESCC). The study group consisted of 1639 patients with thoracic ESCC who underwent oesophagectomy with 3-field lymphadenectomy at the Department of Thoracic Surgery, Fujian Cancer Hospital and whose clinical and survival information were collected.Of the 1639 patients, 668 (40.8%) had no lymph node metastases, 805 (49.1%) had at least 1 positive node but were SCLN-negative, and 166 (10.1%) had SCLN metastases. The 5-year survival rate was 74.1% for node-negative patients, 44.3% for node-positive patients without SCLN metastases, and 33.7% for patients with SCLN metastases. A comparison of the 5-year survival rates among patients with SCLN metastases revealed that the SCLN-positive group was more similar to the N2 group (P = 0.342) than to the N3 group (P = 0.027). In the multivariate analysis, the male sex (P < 0.001), a higher pT stage (P = 0.005), a poorer degree of pathological differentiation (P = 0.045), and a higher N stage (P < 0.001) retained statistical significance as adverse prognostic factors for overall survival, while SCLN metastasis did not (P = 0.956). The survival benefit of 3-field lymphadenectomy including metastases to SCLNs was indicated in patients with thoracic ESCC. SCLNs appear to be regional nodes similar to other regional lymph nodes.