The nod-like receptor protein 3 (NLRP3) is one of the most characterized inflammasomes, and its genetic variation and functional dysregulation are involved in pathogenesis of several cancers. To systematically evaluate the role of NLRP3 in predicting outcomes of patients with non-small cell lung cancer (NSCLC), we performed a two-phase analysis for associations between genetic variants in NLRP3 inflammasome pathway genes and NSCLC survival by using a published genome-wide association study (GWAS) dataset from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We used multivariate Cox proportional hazards regression analysis with Bayesian false discovery probability (≤0.80) for multiple testing correction to evaluate associations between 20,730 single-nucleotide polymorphisms (SNPs) in 176 genes and overall survival of 1,185 NSCLC patients from the PLCO trial. We further validated the identified significant SNPs in another GWAS dataset with survival data from 984 NSCLC patients of the Harvard Lung Cancer Susceptibility (HLCS) study. The results showed that two independent SNPs in two different genes (i.e., BIRC3 rs11225211 and NRG1 rs4733124) were significantly associated with the NSCLC overall survival, with a combined hazards ratio (HR) of 0.83 [95% confidence interval (CI) = 0.74-0.93 and P = 0.0009] and 1.18 (95% CI = 1.06-1.31) and P = 0.002], respectively. However, further expression quantitative trait loci (eQTL) analysis showed no evidence for correlations between the two SNPs and mRNA expression levels of corresponding genes. These results indicated that genetic variants in the NLRP3 imflammasome pathway gene-sets might be predictors of NSCLC survival, but the molecular mechanisms underlying the observed associations warrant further investigations.
Background. Increasing evidence supports that immune cell infiltration (ICI) patterns play a key role in the tumor progression of lung squamous cell carcinoma (LUSC). However, to date, the immune infiltration picture of LUSC has not been elucidated. Method. TCGA was used to download multiomics data from LUSC samples. At the same time, we included two datasets on lung squamous cell carcinoma, GSE17710 and GSE157010. To reveal the landscape of tumor immune microenvironment (TIME), the ESTIMATE algorithm, ssGSEA approach, and CIBERSORT analysis are used. To quantify the ICI pattern in a single tumor, consistent clustering is used to determine the LUSC subtype based on the ICI pattern, and principal component analysis (PCA) is used to obtain the ICI score. The prognostic value of the Kaplan-Meier curves is confirmed. GSEA (Gene Set Enrichment Analysis) was used to perform functional annotation. To investigate the immunotherapeutic effects of the ICI score, the immunophenotyping score (IPS) is used. Finally, analyze the mutation data with the “maftools” R package. Results. We identified four different immune infiltration patterns with different prognosis and biological characteristics in 792 LUSC samples. The identification of ICI patterns in individual tumors developed under ICI-related characteristic genes based on the ICI score helps to analyze the biological process, clinical results, immune cell infiltration, immunotherapy effects, and genetic variation. Immune failure is indicated by a high ICI score subtype marked by immunosuppression. Patients with low ICI scores have an abundance of efficient immune cells, which corresponds to the immunological activation phenotype and may have therapeutic benefits. The immunophenotypic score was used as a surrogate indicator of immunotherapy results, and samples with low ICI scores obtained significantly higher immunophenotypic scores. Finally, the relationship between the ICI score and tumor mutation burden (TMB) was proven. Conclusion. This study fully clarified the indispensable role of the ICI model in the complexity and diversity of TIME. The quantitative identification of ICI patterns in a single tumor will help draw the picture of TIME and further optimize precision immunotherapy.
Lung cancer cells tend to develop resistance to cisplatin (DDP) during continuous chemotherapy, making it crucial to improve DDP sensitivity to enhance therapeutic outcomes. The levels of miR-149-3p in lung tissues and cells, as well as the biological behaviors of lung cancer cells, were analyzed. H446/DDP and A549/DDP cell lines were established to investigate how miR-149-3p affects lung cancer cells' sensitivity to DDP. Bioinformatics analysis predicted transmembrane serine protease 4 (TMPRSS4) as a downstream target of miR-149-3p, which was subsequently confirmed. Western blot analysis was used to examine proteins related to migration, invasion, apoptosis, and TMPRSS4 expression. Additionally, a subcutaneous graft tumor model in nude mice was created to assess the impact of miR-149-3p on tumor growth. In lung cancer tissues and cells, miR-149-3p expression was reduced, while TMPRSS4 expression was elevated. Overexpression of miR-149-3p inhibited cancer progression, promoted apoptosis, and enhanced the chemosensitivity of lung cancer cells to DDP. Moreover, miR-149-3p negatively regulated TMPRSS4, reducing malignancy-associated characteristics of lung cancer cells and further improving their DDP sensitivity. In vivo, high miR-149-3p expression increased the chemosensitivity of cancer cells. In conclusion, miR-149-3p suppresses the aggressive progression of lung cancer by directly downregulating TMPRSS4 and enhances the responsiveness of lung cancer cells to DDP.
Background.Pituitary adenoma is one of the most common intracranial neoplasms, and its primary treatment is endoscopic endonasal transsphenoidal tumorectomy.Postoperative hypokalemia in these patients is a common complication, and is associated with morbidity and mortality.This study aimed to analyze the etiopathology of postoperative hypokalemia in pituitary adenomas after endoscopic transsphenoidal surgery. Methods and Materials. This retrospective study included 181 pituitary adenomas confirmed by histopathology.Unconditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Repeated measures ANOVA was used to analyze change in serum potassium levels at different time points. Results.Multiple Logistic regression analysis revealed that only ACTH-pituitary adenoma (OR=4.92,95%CI: 1.18-20.48,P=0.029) had a significant association with postoperative hypokalemia.Moreover, the overall mean serum potassium concentration was significantly lower in the ACTH versus the non-ACTH group (3.34 mmol/L vs. 3.79 mmol/L, P=0.001).Postoperative hypokalemia was predominantly found in patients with ACTH-pituitary adenoma (P=0.033).Conclusions.ACTH-pituitary adenomas may be an independent factor related postoperative hypokalemia in patients despite conventional potassium supplementation in the immediate postoperative period.
Objective
To explore the anatomical features of lymph node reflux status for pulmonary lobe and pulmonary segment.
Methods
Nine adult cadavers were treated with anatomical latex filler for thoracic lymph node perfusion. Then anterior mediastinum, middle mediastinum, posterior mediastinum lymph nodes were dissected and removed, as well as the upper, middle, lower of the right pulmonary lobe and pulmonary segments, and the upper, lower left pulmonary lobe and pulmonary segments, in addition with hilar lymph nodes. lymph node distribution, number and lymphatic reflux status were observed carefully.
Results
A total of 212 mediastinal lymph nodes were observed in the specimens, with an average of 23.5. The number of lymph nodes was the highest in the tracheal traction (7) and the lower right trachea (4R), followed by the right tracheal (10R), the left bronchus (10L) and the main pulmonary artery window area (5) lymph nodes. The mediastinal area had the largest lymph nodes in the subduction area (7), followed by the right tracheal bronchial (10R) lymph nodes. Lymph nodes increased gradually, and the right side was greater than the left, which means that the lower was greater than the upper and the right was greater than the left. Left lung and right lung pulmonary lymph nodes were generally in accordance with the sub-lymph node→segment lymph nodes→leaf lymph nodes→leaf lymph nodes/hilar lymph nodes and tracheal traction; right upper lobe, middle lobe and hilar lymph nodes usually flowed back to the mediastinal lymph nodes. The lower lobe flowed back to the mediastinal lymph nodes. While the left upper lobe general drained to the main-pulmonary artery window lymph nodes and tracheal traction, the lower lobe was also draining to the mediastinal lymph nodes.
Conclusions
The lobar and mediastinal lymphatic reflux has a certain regularity, which provides anatomical basis for the choice of lobular specific/systemic lymph node dissection.
Key words:
Lung cancer; Lymph node dissection; Specific lymph node dissection
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