Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. Pyroptosis could regulate tumour cell proliferation, invasion, and metastasis, thereby affecting the prognosis of cancer patients. However, the role of pyroptosis-related genes (PRGs) in LUAD remains unclear. In our study, comprehensive bioinformatics analysis was performed to construct a prognostic gene model and ceRNA network. The correlations between PRGs and tumour-immune infiltration, tumour mutation burden, and microsatellite instability were evaluated using Pearson’s correlation analysis. A total of 23 PRGs were upregulated or downregulated in LUAD. The genetic mutation variation landscape of PRG in LUAD was also summarised. Functional enrichment analysis revealed that these 33 PRGs were mainly involved in pyroptosis, the NOD-like receptor signalling pathway, and the Toll-like receptor signalling pathway. Prognosis analysis indicated a poor survival rate in LUAD patients with low expression of NLRP7, NLRP1, NLRP2, and NOD1 and high CASP6 expression. A prognostic PRG model constructed using the above five prognostic genes could predict the overall survival of LUAD patients with medium-to-high accuracy. Significant correlation was observed between prognostic PRGs and immune-cell infiltration, tumour mutation burden, and microsatellite instability. A ceRNA network was constructed to identify a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis in LUAD. In conclusion, we performed a comprehensive bioinformatics analysis and identified a prognostic PRG signature containing five genes (NLRP7, NLRP1, NLRP2, NOD1, and CASP6) for LUAD patients. Our results also identified a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis, which may also play an important role in the progression of LUAD. Further study needs to be conducted to verify this result.
Background Esophageal cancer is a relatively rare cancer. However, its death rate is not to be taken lightly. Accumulating evidence indicates circular RNA (circRNA) is implicated in cancer development. The objective of this study was to unveil the role of circ_0001273 in esophageal cancer (EC). Methods For expression analysis of circ_0001273, miR‐622 and solute carrier family 1 member 5 (SLC1A5), quantitative real‐time PCR (qPCR) and Western blot were conducted. Cell proliferation was evaluated by cell counting kit‐8 (CCK‐8), EdU and colony formation assays. Cell apoptosis and cell migration were investigated using flow cytometry assay and wound healing assay. Glutamine metabolism was assessed by glutamine consumption and glutamate production using matched kits. The predicted binding relationship between miR‐622 and circ_0001273 or SLC1A5 was validated by dual‐luciferase reporter assay. An in vivo xenograft model was established to determine the role of circ_0001273 on tumor growth. Results Circ_0001273 was upregulated in EC tumor tissues and cells. Knockdown of circ_0001273 repressed EC cell proliferation, migration, epithelial‐mesenchymal transition (EMT) and glutamine metabolism. Circ_0001273 knockdown also blocked tumor development in animal models. MiR‐622 was targeted by circ_0001273, and its inhibition reversed the functional effects of circ_0001273 knockdown. SLC1A5 was a target gene of miR‐622, and circ_0001273 targeted miR‐622 to positively regulate SLC1A5 expression. The inhibitory effects of miR‐622 enrichment on EC cell proliferation, migration, EMT and glutamine metabolism were recovered by SLC1A5 overexpression. Conclusion Circ_0001273 high expression contributed to EC progression via modulating the miR‐622/SLC1A5 signaling axis.
Background: To evaluate the short-term efficacy of azygos arch-sparing McKeown minimally invasive esophagectomy (McKeown-MIE). Methods: We retrospectively analyzed the clinical data of 221 patients with thoracic esophageal squamous cell carcinoma who underwent McKeown-MIE at the Department of Thoracic Surgery of Gaozhou People'sHospital from August 1, 2017 to September 30, 2019. According to whether the azygos arch was preserved or not, the patients were assigned to one of two groups: the preservation group (40 cases) and the ligation group (181 cases). Within 3 months of the operation, the perioperative outcomes and the postoperative short-term efficacy of the two groups were compared.Results: After propensity score (PS) matching, 40 pairs of patients were matched successfully. Between the two groups, there were no statistical difference in intraoperative blood loss, the number of lymph nodes dissected, thoracic drainage duration, fasting time, postoperative hospital stay time, and major postoperative complications (P>0.05). Compared with the ligation group, patients in the preservation group had a shorter intensive care unit (ICU) stay time, a shorter operative time, a lower volume of postoperative thoracic drainage (both the first 3 days and overall) following surgery, a tubular stomach that had a smaller caliber, and a lower incidence of tubular gastric malpositioning (P<0.05). Conclusions: Preserving the azygos arch during a McKeown-MIE is safe and feasible. Doing so, not only effectively restricts the expansion of the gastric conduit, leading to a lower incidence of malpositioning, but also dramatically reduces postoperative thoracic drainage, and ICU stay time.
Background The response rate and survival benefit of immunotherapy vary among patients, implying specific immune status of an individual could be associated with the effect of immunotherapy. However, in-depth studies of immune subtypes (ISs), immune landscape and tumour microenvironment of oesophageal cancer (ESCA) and their clinical implications are less reported. Methods We first accessed data from publicly available databases and preprocessed it based on a standard protocol. Then, ISs were identified by unsupervised learning. Thereafter, the association of these ISs and tumour mutation burden (TMB), biomarkers of chemotherapy-induced immune response, tumour markers were also assessed. In addition, the immune characteristics, immune landscape, co-expression network of immune genes, and clinical implications were visualized and analysed. Results We identified three immunoclusters based on immune-associated genes with intra-class heterogeneity and prognostic value. Cluster-specific associations with TMB, markers of chemotherapy-induced immune response, and tumour markers were revealed. A 4-gene signature (risk score= −0.16514291× BHLHE22 −0.03964046× MXRA8 −0.15242778× SLIT2 −0.05553572× SPON1 ) based on co-expressed genes in the immunoclusters was developed and externally validated. Conclusions In summary, we identified clinically relevant immunoclusters in both adenocarcinoma and squamous cell carcinoma of oesophagus, revealing the necessity of assessing the complexity and diversity of immune microenvironment for cancer immunotherapy.
Background: Traditional McKeown minimally invasive esophagectomy (MIE-McKeown) with resection of the thoracic and abdominal branches of vagus nerve, the azygos vein and the bronchial artery, is notorious for high complications incidence and sharply decreased quality of life (QoL) postoperatively in esophageal cancer (EC). Recently, reports of preservation of azygos vein arch or the vagus nerve have shown the advantages of decreasing postoperative complication incidence. However, the modified MIE-McKeown with preservation of azygos vein arch, vagus nerve and the bronchial artery has never been investigated in EC. In the present study, we aimed to compare the short-term efficacy and postoperative QoL between modified MIE-McKeown and traditional MIE-McKeown. Methods: A total of 218 eligible patients with esophageal squamous cell carcinoma (ESCC) who met our inclusion criteria between October 2018 and January 2022 in our center were retrospectively enrolled and divided into modified MIE-McKeown group (N=48) and the control group with traditional MIE-McKeown (N=170) according to their surgical procedure. We compared the perioperative parameters (e.g., operation time and postoperative complications) between the two groups. The core quality of life questionnaire (QLQ-C30) (version 3.0) and the EC-specific QoL assessment form (QLQ-OES18) were used to evaluate the QoL in the 2 groups at 1 and 3 months after operation.Results: There were no significant differences in baseline characteristics between modified MIE-McKeown group and the control group. Compared with the control group, the modified MIE-McKeown group had significantly lower postoperative drainage volume (551.46±249.45 vs. 812.96±405.82; P<0.001) and a lower incidence of thoracic stomach syndrome (TSS; P=0.001). The bleeding loss in the modified MIE-McKeown group was lower than that in the control group (56.88±20.44 vs. 83.18±97.93; P=0.066), but not significantly. There were no significant differences observed in postoperative complications and other perioperative parameters between the two groups. The results of QLQ-C30 and QLQ-OES18 questionnaire revealed that the modified MIE-McKeown group was associated with better physical function, better global health status and milder symptoms of gastroesophageal reflux and cough. Conclusions:The modified MIE-McKeown is a safe and efficient procedure and has the potential to improve postoperative health status of patients with EC.
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