Clinical significance of postoperative folate receptor-positive circulating tumor cells (FR + CTCs) for long-term prognosis in patients with invasive adenocarcinoma (IAC) of the lung.

BACKGROUND: The aim of the study was to evaluate the prognostic value of postoperative folate receptor-positive circulating tumor cell (FR + CTC) detection in patients with stage I-III invasive adenocarcinoma (IAC) treated with surgery. METHODS: Patients with lung adenocarcinoma (LUAD) who underwent surgical resection in Peking University Cancer Hospital and received postoperative FR + CTC analysis from July 2016 to January 2021 were retrospectively collected. Comparisons between or among groups were made using the Kruskal-Wallis or Mann-Whitney U tests. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression analyses were performed to explore the factors predicting recurrence and survival. RESULTS: There were significant differences between the high and low groups in terms of age (p = 0.002), postoperative CA199 (p = 0.038), and postoperative SCC (p = 0.024). There were no significant differences in the other indicators (all p>0.05). N stage 1, N stage 2, and neoadjuvant therapy (NAT) were independent risk factors for disease recurrence and death; pleural invasion (PI), and nerve invasion were independent risk factors for death. The Kaplan-Meier curve showed a notable trend for a worse disease-free survival (DFS) or overall survival (OS) for patients with high levels of FR + CTCs in our study, but none of these were statistically significant. CONCLUSION: The detection of FR + CTCs postoperatively was an independent predictor of recurrence in patients treated for stage I-III IAC. Standardized detection methods and optimal time points for assessment should be established in future studies.

Body composition and metabolic syndrome in patients with type 1 diabetes.

BACKGROUND: In recent years, the prevalence of obesity and metabolic syndrome in type 1 diabetes (T1DM) patients has gradually increased. Insulin resistance in T1DM deserves attention. It is necessary to clarify the relationship between body composition, metabolic syndrome and insulin resistance in T1DM to guide clinical treatment and intervention. AIM: To assess body composition (BC) in T1DM patients and evaluate the relationship between BC, metabolic syndrome (MS), and insulin resistance in these indi-viduals. METHODS: A total of 101 subjects with T1DM, aged 10 years or older, and with a disease duration of over 1 year were included. Bioelectrical impedance analysis using the Tsinghua-Tongfang BC Analyzer BCA-1B was employed to measure various BC parameters. Clinical and laboratory data were collected, and insulin resistance was calculated using the estimated glucose disposal rate (eGDR). RESULTS: MS was diagnosed in 16/101 patients (15.84%), overweight in 16/101 patients (15.84%), obesity in 4/101 (3.96%), hypertension in 34/101 (33.66%%) and dyslipidemia in 16/101 patients (15.84%). Visceral fat index (VFI) and trunk fat mass were significantly and negatively correlated with eGDR (both P < 0.001). Female patients exhibited higher body fat percentage and visceral fat ratio compared to male patients. Binary logistic regression analysis revealed that significant factors for MS included eGDR [P = 0.017, odds ratio (OR) = 0.109], VFI (P = 0.030, OR = 3.529), and a family history of diabetes (P = 0.004, OR = 0.228). Significant factors for hypertension included eGDR (P < 0.001, OR = 0.488) and skeletal muscle mass (P = 0.003, OR = 1.111). Significant factors for dyslipidemia included trunk fat mass (P = 0.033, OR = 1.202) and eGDR (P = 0.037, OR = 0.708). CONCLUSION: Visceral fat was found to be a superior predictor of MS compared to conventional measures such as body mass index and waist-to-hip ratio in Chinese individuals with T1DM. BC analysis, specifically identifying visceral fat (trunk fat), may play an important role in identifying the increased risk of MS in non-obese patients with T1DM.

Construction of the metabolism-related models for predicting prognosis and infiltrating immune phenotype in lung squamous cell carcinoma.

Purpose: Cancers often display disorder metabolism, which closely related to the poor outcome of patients. We aimed to establish prognostic models using metabolism-associated genes, and identify the key factor involved in metabolism in lung squamous cell carcinoma (LUSC). Materials and Methods: R package 'TCGA biolinks' was used to download the mRNA sequencing data of LUSC from TCGA. The clusterProfiler package was performed to analyze biological pathways. The online tool GEPIA2 and cox regression method were applied to identify the two gene lists associated with metabolism and prognosis of LUSC. The lasso modeling was conducted to establish prognostic models. The quantiseq method was used to identify the cellular abundance of expression matrix in TCGA-LUSC dataset. Immunohistochemistry and western blotting were done to evaluate the STXBP1 expression in LUSC samples. Lactate assay and ATP detection were performed to assess metabolic effect, and CCK8 assay was done to test cell proliferation in the LUSC cells with overexpression and suppression of STXBP1. Results: Two lists of survival-metabolism-associated genes (11 and 28 genes) were identified and applied in the prognostic model 1 and model 2 construction from TCGA-LUSC dataset. High-risk LUSC patients associated with poor survival in the training cohort and the test cohort of both model 1 and model 2. Higher ROC values for 10- year survival was shown in model 2 than in model 1. In addition, macrophage M1, macrophage M2, neutrophil, and T regulatory cell were enriched in the high-risk group of model 2. STXBP1 was the only optimized gene in both model 1 and model 2, and related to the poor outcome of LUSC patients. Furthermore, STXBP1 associated with infiltrating immune cells, and increased lactate, ATP levels, and cell proliferation. Conclusion: Our finding provides the metabolism-associated models to predict prognosis of LUSC patients. STXBP1, as the key optimized gene in the model, promotes metabolic progress to increase lactate and ATP levels in LUSC cells.

Machine learning-based establishment and validation of age-related patterns for predicting prognosis in non-small cell lung cancer within the context of the tumor microenvironment.

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 80% of cases. The impact of aging on clinical outcomes in NSCLC remains poorly understood, particularly with respect to the immune response. In this study, we explored the effects of aging on NSCLC using 307 genes associated with human aging from the Human Ageing Genomic Resources. We identified 53 aging-associated genes that significantly correlate with overall survival of NSCLC patients, including the clinically validated gene BUB1B. Furthermore, we developed an aging-associated enrichment score to categorize patients based on their aging subtypes and evaluated their prognostic and therapeutic response values in LC. Our analyses yielded two aging-associated subtypes with unique profiles in the tumor microenvironment, demonstrating varying responses to immunotherapy. Consensus clustering based on transcriptome profiles provided insights into the effects of aging on NSCLC and highlighted the potential of personalized therapeutic approaches tailored to aging subtypes. Our findings provide a new target and theoretical support for personalized therapeutic approaches in patients with NSCLC, offering insights into the potential impact of aging on cancer outcomes.

Hsa_circ_0007312 Promotes Third-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance through Pyroptosis and Apoptosis via the MiR-764/MAPK1 Axis in Lung Adenocarcinoma Cells.

Purposes: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) used for patients with gefitinib (first-generation EGFR-TKI) resistance, but osimertinib resistance inevitably occurs. Therefore, it is necessary to explore the mechanisms of osimertinib resistance. Materials and Methods: We performed quantitative real-time polymerase chain reaction to detect hsa_circ_0007312 (circ7312), miR-764, and MAPK1 expressions in tissues and cells. Western blotting was used to detect protein levels in cells. Cell Counting Kit-8, apoptotic, and Transwell assays were used to explore biological functions. Luciferase assays were used to identify the interactions between circ7312 and miR-764, MAPK1 and miR-764. A xenograft experiment was performed to clarify the role of circ7312 in vivo. Public datasets were used to identify the relation between circ7312 expression and the cell half maximal inhibitory concentration value of osimertinib in 41 lung adenocarcinoma cell lines. The Student t-test, Kaplan-Meier analysis, and Pearson correlation analysis were used in data analysis. Results: We found that circ7312 knockdown increased miR-764 expression and decreased MAPK1 expression, and circ7312 regulated MAPK1 by sponging miR-764. In addition, high circ7312 expression has significant positive correlation with osimertinib IC50 values, circ7312 knockdown decreased the cell half maximal inhibitory concentration value of osimertinib and increased pyroptosis and apoptosis by sponging the miR-764/MAPK1 axis. We also found that circ7312 and MAPK1 were highly expressed in tumor tissues and related to poor prognosis. Xenograft experiments revealed that circ7312 knockdown decreased osimertinib resistance in vivo. Conclusion: We demonstrated that the inhibition of circ7312 decreased osimertinib resistance by promoting pyroptosis and apoptosis via the miR-764/MAPK1 axis, providing a novel target for osimertinib resistance therapy.

Preoperative Patient and Lesion Features Are Valuable for Predicting the Prognosis of Resectable Peripheral Non-Small Cell Lung Cancer.

OBJECTIVE: The aim of the study was to investigate the preoperative factors affecting the survival of patients with resectable peripheral non-small cell lung cancer (NSCLC) to improve the management of NSCLC. METHODS: One hundred ninety-nine patients with peripheral NSCLC diagnosed clinically without lymph node metastasis were enrolled. The preoperative computed tomography characteristics of the tumors were retrospectively analyzed and the preoperative clinical data were collected. The size of the solid components for lung adenocarcinomas containing ground-glass opacity (GGO) component were measured. Kaplan-Meier method with log-rank test was used to compare overall survival (OS) between groups. Univariate and multivariate cox regression analyses were used to identify prognostic factors. RESULTS: Survival analysis showed that the OS of the group with a tumor of 3 cm or less was longer than that of the group with a tumor greater than 3 cm, the OS of the group with GGO component was superior to that of the group without GGO component, and the OS of the group with elevated carcinoembryonic antigen (CEA) levels was inferior to that of the group with normal CEA levels. Multivariate Cox regression analysis showed that tumor size, density, and preoperative CEA level were independent factors affecting OS, with hazard ratios of 2.401, 0.457, and 1.948, respectively. The analysis of lung adenocarcinomas with GGO component demonstrated that the mean size of the solid component in the nonsurviving group was significantly larger than that in the surviving group (mean, 23 ± 6.4 vs 8.6 ± 7.0 mm). The area under the receiver operating characteristic curve of the solid component size of lung cancer containing GGO component to predict postoperative death was 0.932. CONCLUSIONS: Tumor size, density, and preoperative CEA level were independent prognostic factors of patients with resectable peripheral NSCLCs. Preoperative computed tomography findings can be valuable for predicting the prognosis of patients with NSCLC after surgery.

Mucormycosis spondylodiscitis after lumbar disc puncture.

Vertebral osteomyelitis due to mucormycosis is a rare but fulminant and fatal disease. Only one case has been reported in literature, with postmortem diagnosis. The present paper reports a female case of mucormycosis spondylodiscitis and vertebral osteomyelitis after lumbar disc puncture and radio frequency nucleoplasty. She subsequently underwent two surgical debridements, continuous local irrigation and drainage, together with local and systemic Amphotericin B treatments. The infection was controlled 4 months after the second debridement; however, there was no improvement in the neurological function at the most recent follow-up, 16 months after the surgery. The experience of this patient, though a single case, supports early recognition, surgical debridement, systemic and local antifungal treatment, closed irrigation and drainage as the keys to successful treatment.