Identification and validation of tryptophan metabolism-related lncRNAs in lung adenocarcinoma prognosis and immune response.

BACKGROUND: Tryptophan (Trp) is an essential amino acid. Increasing evidence suggests that tryptophan metabolism plays a complex role in immune escape from Lung adenocarcinoma (LUAD). However, the role of long non-coding RNAs (lncRNAs) in tryptophan metabolism remains to be investigated. METHODS: This study uses The Cancer Genome Atlas (TCGA)-LUAD dataset as the training cohort, and several datasets from the Gene Expression Omnibus (GEO) database are merged into the validation cohort. Genes related to tryptophan metabolism were identified from the Molecular Signatures Database (MSigDB) database and further screened for lncRNAs with Trp-related expression. Subsequently, a prognostic signature of lncRNAs related to tryptophan metabolism was constructed using Cox regression analysis, (Least absolute shrinkage and selection operator regression) and LASSO analysis. The predictive performance of this risk score was validated by Kaplan-Meier (KM) survival analysis, (receiver operating characteristic) ROC curves, and nomograms. We also explored the differences in immune cell infiltration, immune cell function, tumor mutational load (TMB), tumor immune dysfunction and exclusion (TIDE), and anticancer drug sensitivity between high- and low-risk groups. Finally, we used real-time fluorescence quantitative PCR, CCK-8, colony formation, wound healing, transwell, flow cytometry, and nude mouse xenotransplantation models to elucidate the role of ZNF8-ERVK3-1 in LUAD. RESULTS: We constructed 16 tryptophan metabolism-associated lncRNA prognostic models in LUAD patients. The risk score could be used as an independent prognostic indicator for the prognosis of LUAD patients. Kaplan-Meier survival analysis, ROC curves, and risk maps validated the prognostic value of the risk score. The high-risk and low-risk groups showed significant differences in phenotypes, such as the percentage of immune cell infiltration, immune cell function, gene mutation frequency, and anticancer drug sensitivity. In addition, patients with high-risk scores had higher TMB and TIDE scores compared to patients with low-risk scores. Finally, we found that ZNF8-ERVK3-1 was highly expressed in LUAD tissues and cell lines. A series of in vitro experiments showed that knockdown of ZNF8-ERVK3-1 inhibited cell proliferation, migration, and invasion, leading to cell cycle arrest in the G0/G1 phase and increased apoptosis. In vivo experiments with xenografts have shown that knocking down ZNF8-ERVK3-1 can significantly inhibit tumor size and tumor proliferation. CONCLUSION: We constructed a new prognostic model for tryptophan metabolism-related lncRNA. The risk score was closely associated with common clinical features such as immune cell infiltration, immune-related function, TMB, and anticancer drug sensitivity. Knockdown of ZNF8-ERVK3-1 inhibited LUAD cell proliferation, migration, invasion, and G0/G1 phase blockade and promoted apoptosis.

Association of systemic inflammatory markers with postoperative arrhythmias in esophageal cancer: a propensity score matching.

BACKGROUND: The severity and prognosis of an array of inflammatory diseases have been predicted using systemic inflammatory indices, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), derived neutrophil-to-lymphocyte ratio (dNLR), and systemic immune inflammation index (SII). The purpose of this study was to examine the association between systemic inflammatory markers and postoperative arrhythmias (PA) in esophageal cancer patients. METHODS: In the study, laboratory-related parameters were gathered and examined in 278 patients (non-PA = 221, PA = 57). Fit separate propensity score matching (PSM) within subgroup strata (surgery approaches); match within strata, and aggregate for main analysis. Finally, we established a 1:1(57:57) model. The ability of inflammatory makers on the first post-esophagectomy day to distinguish PA from postoperative non-arrhythmia (non-PA) by receiver operating characteristic (ROC) analysis. RESULTS: On the first post-esophagectomy day, there was a greater difference between PA and non-PA in terms of white blood cell (WBC) and neutrophil (NE), Neutrophil percentage (NE%), NLR, dNLR, LMR, and SII. After PSM, the following variables were substantially different between non-PA and PA: NE%, NLR, dNLR, and SII. It was found that WBC, NE, NE%, NLR, dNLR, LMR, and SII had the area under the curve (AUC) that was higher than 0.500 in ROC analysis, with NLR and SII having the highest AUC (AUC = 0.661). The indicators were subjected to binary logistic regression analysis, which increased the indicators' predictive ability (AUC = 0.707, sensitivity = 0.877). CONCLUSION: On the first post-esophagectomy day, systemic inflammatory indicators were significantly correlated with both PA and non-PA, and high SII and NLR are reliable markers of PA.

Combining fecal microbiome and metabolomics reveals diagnostic biomarkers for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites from patients with ESCC have not been adequately studied and discussed. In this study, 40 fecal samples (20 from ESCC patients and 20 from healthy controls) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The data sets were analyzed individually and synthesized using various bioinformatics methods. Alpha and beta diversity indicated significant differences in microbial diversity and abundance between ESCC and healthy control feces. At the genus level, the abundance of Phascolarctobacterium, Sutterella, and Streptococcus was significantly increased in ESCC. At the genus level, linear discriminant analysis effect size identified two biomarkers: Bacteroides_stercoris and Prevotella_copri. Untargeted metabolomics analysis revealed 307 differential metabolites between ESCC and healthy control feces, with indoles and derivatives, tropane alkaloids, lipids, and lipid-like molecules in higher relative abundance in ESCC feces than in healthy control feces. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that unsaturated fatty acids (FAs), ascorbate and aldarate metabolism, and hypoxia-inducible factor 1 signaling pathway were significantly associated with differential metabolite. Phenylethanolamine and despropionyl p-fluoro fentanyl could be used as reliable biomarkers to differentiate ESCC from healthy control. The correlation analysis showed that Prevotella may be involved in the synthesis of fatty acyl, carboxylic acids and derivatives, benzenes and substituted derivatives, organic oxygenates, and indoles and derivatives as metabolites. Fusicatenibacter and Lachnospira may be involved in the degradation of indoles and derivatives. Alistipes, Agathobacter, and Parabacteroides may be involved in the synthesis of indoles and derivatives with strong contributions. There is an intricate relationship between the gut microbiome and the levels of several metabolites (e.g., fatty acyls, carboxylic acids and derivatives, indoles, and derivatives). Microbial-associated metabolites can be used as diagnostic biomarkers in therapeutic exploration. Further analysis revealed that Prevotella, Alistipes, Agathobacter, and Parabacteroides might promote ESCC by regulating the synthesis of indoles and their derivatives. The results of this study provide favorable evidence for the early diagnosis of ESCC and subsequent individualized treatment and targeted interventions.IMPORTANCEWe describe for the first time the differences in fecal microbiome composition and metabolites between patients with esophageal squamous cell carcinoma (ESCC) and healthy controls by 16S rRNA gene sequencing and untargeted metabolomics. The results of this study provide a favorable basis for the early diagnosis of ESCC and subsequent targeted interventional therapy.

Right upper lobectomy after immunotherapy for primary malignant melanoma of the lung: a case report and literature review.

Background: Malignant melanoma is a malignant tumor of melanocytes. All body organs can be invaded by it; however, the skin is the most common site of invasion. Melanomas involving the lungs are almost always metastatic and it is extremely rare to find a true primary malignant melanoma of the lung (PMML). Compared to cutaneous melanoma, mucosal melanoma has a different biology and clinical appearance. Since there are no standards for the diagnosis and treatment of PMML, it is treated differently. We reported a patient with PMML underwent surgery after programmed cell death 1 (PD-1) immunotherapy. Case Description: A 62-year-old female patient presented with an occupying lesion in the right upper lung lobe found on physical examination. A computed tomography (CT) scan was done, and the results showed a lobulated soft tissue mass shadow of roughly 54 mm × 50 mm in the upper lobe of the right lung. The histological results of a CT-guided percutaneous lung biopsy were consistent with malignant melanoma. She was identified as having primary melanoma of the lung after undergoing a full physical examination to rule out occult primary tumor metastases. The patient received a total of 33 cycles of immunotherapy (PD-1). We did a right upper lung lobectomy after shrinking the melanoma in the right lung's upper lobe to a size of 16 mm × 10 mm. After the operation, the patient was monitored for 6 months and made a full recovery without recurrence. Conclusions: The preoperative immune system in combination with a surgical procedure may boost patients' chances of survival. These findings need to be confirmed in more clinical research.