Single-cell aggrephagy-related patterns facilitate tumor microenvironment intercellular communication, influencing osteosarcoma progression and prognosis.

Osteosarcoma, a common malignant tumor in children, has emerged as a major threat to the life and health of pediatric patients. Presently, there are certain limitations in the diagnosis and treatment methods for this disease, resulting in inferior therapeutic outcomes. Therefore, it is of great importance to study its pathogenesis and explore innovative approaches to diagnosis and treatment. In this study, a non-negative matrix decomposition method was employed to conduct a comprehensive investigation and analysis of aggregated autophagy-related genes within 331,394 single-cell samples of osteosarcoma. Through this study, we have elucidated the intricate communication patterns among various cells within the tumor microenvironment. Based on the classification of aggregated autophagy-related genes, we are not only able to more accurately predict patients' prognosis but also offer robust guidance for treatment strategies. The findings of this study hold promise for breakthroughs in the diagnosis and treatment of osteosarcoma, intervention of aggrephagy is expected to improve the survival rate and quality of life of osteosarcoma patients.

Pathomics and single-cell analysis of papillary thyroid carcinoma reveal the pro-metastatic influence of cancer-associated fibroblasts.

BACKGROUND: Papillary thyroid carcinoma (PTC) is globally prevalent and associated with an increased risk of lymph node metastasis (LNM). The role of cancer-associated fibroblasts (CAFs) in PTC remains unclear. METHODS: We collected postoperative pathological hematoxylin-eosin (HE) slides from 984 included patients with PTC to analyze the density of CAF infiltration at the invasive front of the tumor using QuPath software. The relationship between CAF density and LNM was assessed. Single-cell RNA sequencing (scRNA-seq) data from GSE193581 and GSE184362 datasets were integrated to analyze CAF infiltration in PTC. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of CD36+CAF in two PTC cell lines, TPC1 and K1. RESULTS: A significant correlation was observed between high fibrosis density at the invasive front of the tumor and LNM. Analysis of scRNA-seq data revealed metastasis-associated myoCAFs with robust intercellular interactions. A diagnostic model based on metastasis-associated myoCAF genes was established and refined through deep learning methods. CD36 positive expression in CAFs can significantly promote the proliferation, migration, and invasion abilities of PTC cells, while inhibiting the apoptosis of PTC cells. CONCLUSION: This study addresses the significant issue of LNM risk in PTC. Analysis of postoperative HE pathological slides from a substantial patient cohort reveals a notable association between high fibrosis density at the invasive front of the tumor and LNM. Integration of scRNA-seq data comprehensively analyzes CAF infiltration in PTC, identifying metastasis-associated myoCAFs with strong intercellular interactions. In vitro experimental results indicate that CD36 positive expression in CAFs plays a promoting role in the progression of PTC. Overall, these findings provide crucial insights into the function of CAF subset in PTC metastasis.

Clinical Characteristics and Risk Factors of Noninfectious Fever after Thoracic Endovascular Aortic Repair of Acute Type B Aortic Dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) is gradually becoming a first-line treatment of complicated acute type B aortic dissection (ATBAD). Interestingly, according to years of experience in the treatment of ATBAD, we found that patients with ATBAD often had unexplained noninfectious fever after TEVAR. This study aims to explore its clinical characteristics and independent risk factors. METHODS: From January 2016 to September 2021, 211 consecutive patients treated electively by TEVAR for ATBAD were included. The entry tears in all patients originated in the distal to the left subclavian artery (LSA). All patients were diagnosed with ATBAD for the first time. The definition of fever in this study was that the body temperature of patients after TEVAR exceeds 38°C. RESULTS: A total of 211 patients (53.62 ± 11.34 years, 81% men) were included in the analysis. To compare patients who did and did not have post-TEVAR fever, they were respectively classified as the fever group and the nonfever group. Fever was diagnosed in 115 (55%) patients. Preoperatively, statistical differences were recorded in age (P = 0.023) and red blood cell (P = 0.037). Age <60 years [odds ratio (OR) 2.194, 95% confidence interval (CI) 1.147-4.196, P = 0.018] and duration of the operation >3 hr (OR 3.586, 95% CI 1.133-11.350, P = 0.03) were positively associated with fever. In the comparison of preoperative and postoperative experimental data, the changes in white blood cell (P = 0.046) and platelet (P = 0.007) of the 2 groups were significantly different. Hospital stay (P = 0.009) and postoperative hospital stay (P < 0.001) in the fever group were significantly prolonged. There was no difference in survival in the mid- and long-term follow-up between the 2 groups. CONCLUSIONS: Noninfectious fever occurs in more than half of the patients after TEVAR (115/211, 54.5%). Patients in the fever group are younger. Age <60 years and duration of the operation >3 hr are independent risk factors for noninfectious fever in patients with ATBAD after TEVAR fever. Noninfectious fever after TEVAR may lead to prolonged hospital stay. However, it did not affect mid- and long-term prognosis.

Age-related differences in acute aortic dissection.

OBJECTIVE: The present study investigated the differences in clinical characteristics, treatments, and outcomes of patients with acute aortic dissection (AAD) in different age groups. METHODS: The present single-center retrospective study was conducted from August 2014 to August 2020. The patients were divided into three groups: age <45 years (young group), age 45 to 59 years (middle-age group), and age >59 years (elderly group). Type A (TAAD) and type B (TBAD) aortic dissection were evaluated separately using the latest definitions. RESULTS: The mean age at onset was 52.4 years in our cohort of 602 patients. The young group included a large proportion of male patients (86%). The body mass index and body surface area were higher in the young group. The proportion of non-true lumen blood supply of branches on the abdominal aorta in the young group (27%-55%) was greater than that in the others. In the young group, the distal extent of dissection in 84% of TAAD and 89% of TBAD exceeded the abdominal aortic branch cluster (AABC) compared with 36% of TAAD and 58% of TBAD in the elderly group. The multivariate analysis revealed that age <45 years (odds ratio, 5.15; P < .001) and D-dimer level (odds ratio, 1.05; P = .001) were risk factors for intimal flap tear exceeding the AABC. The proportion of visceral and lower limb malperfusion increased from 4.8% to 36.9% as the intimal flap tear exceeded the AABC. CONCLUSIONS: Compared with middle-age and elderly patients, young patients with AAD had two characteristics (ie, obesity and an intimal flap that had frequently exceeded the branches of the aorta). These two factors resulted in a greater proportion of non-true lumen blood supply, increased visceral and lower limb malperfusion, and an increase in potential associated risks.

Influence of Abdominal Aortic Calcification on the Distal Extent and Branch Blood Supply of Acute Aortic Dissection.

BACKGROUND: This study aimed to investigate the influence of abdominal aortic calcification on the distal extent, blood supply, and mid-term outcomes of acute aortic dissection (AAD). METHODS: This single-centre retrospective study was conducted from August 2014 to May 2021. The aortic calcification index was used to evaluate abdominal aortic calcification. The standardized method provided by the Society for Vascular Surgery was used to evaluate the distal extent of AAD. Patients were divided into 3 groups as per the degree of calcification: no calcification (NC), low calcification (LC), and high calcification (HC). RESULTS: In a cohort of 723 patients, abdominal aortic calcification was present in 424 (58.6%) patients. The prevalence of coronary heart disease increased with the degree of calcification (NC versus LC versus HC: 8.4% vs. 9.5% vs. 19.3%, P < 0.001). The aortic calcification index of the distal extent at zone 9 was higher than that of the distal extent exceeding zone 9 (P = 0.001). The proportions of the NC, LC, and HC groups with distal extents exceeding zone 9 were 65.9% vs. 56.2% vs. 37.7%, P < 0.001. In a multivariate logistics analysis, the calcification grade was a protective factor of distal extents exceeding zone 9 (P < 0.001, odds ratio [OR] = 0.592). Hypertension (P = 0.019, OR = 1.559) and D-dimer (P < 0.001, OR = 1.045) were risk factors. There was a higher proportion of branch-vessels on the abdominal aorta supplied by the true lumen in the calcification group (NC versus LC versus HC: 27.8% vs. 43.8% vs. 51.1%, P < 0.001). There were no significant differences in the mid-term outcomes among the groups. CONCLUSIONS: Abdominal aortic calcification could limit the distal extent in patients with AAD and increase the proportion of branch-vessels on the abdominal aorta supplied by the true lumen.

Comprehensive analysis of cellular senescence and immune microenvironment in papillary thyroid carcinoma.

Senescence-induced therapy was previously considered as an effective treatment for tumors, and cellular senescence was initially regarded as an effective mechanism against cancer. However, whether cell senescence-related genes can be used to predict the prognosis of papillary thyroid carcinoma (PTC) and immunotherapy remains unclear. We developed and validated a cell senescence-related signature (CSRS) by analyzing the gene expression of 278 genes related to cellular senescence in 738 patients with PTC. Additionally, further analysis showed that CSRS was a reliable predictor of patient outcomes in combination with immune checkpoint expression and drug susceptibility, and patients with high risk scores may benefit from immunotherapy. The findings of this study demonstrate that CSRS serves as an immunotherapeutic response and prognosis biomarker affecting the tumor immune microenvironment of PTC.

The Prognostic Value and Potential Immune Mechanisms of lncRNAs Related to Immunogenic Cell Death in Papillary Thyroid Carcinoma.

Background: Long non-coding RNAs (lncRNAs) associated with immunogenic cell death (ICD) play a pivotal role in tumorigenesis and offer prognostic insights for papillary thyroid carcinoma (PTC) patients. This study delves into the impact of ICD-related lncRNAs on the prognosis of PTC. Methods: PTC samples were accessed from The Cancer Genome Atlas-Thyroid carcinoma database (TCGA-THCA) and consensus cluster analysis to elucidate the influence of ICD-related lncRNA expression. To gauge the prognostic significance of these lncRNAs, we developed a prognostic model. Additionally, we conducted GO and KEGG enrichment analyses, assessed immune cell infiltration (ICI) using CIBERSORT and ssGSEA, examined immune checkpoint expression, tumor mutation burden (TMB), tumor microenvironment (TME), T-cell dysfunction and exclusion (TIDE), TCIA, and drug sensitivity across various groups. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of LINC00924 in two PTC cell lines, BCPAP and TPC1, transfected with LINC00924 overexpression plasmids. Results: Two distinct clusters demonstrated varying TME, BRAF, NRAS, and ICI characteristics, suggesting potential immune mechanisms in PTC. Our prognostic model identified seven lncRNAs: SRRM2-AS1, AC008556.1, BHLHE40-AS1, EGOT, AL39066.1, LINC00924, and PICART1. The expression of ICD-related lncRNAs correlated with progression-free interval (PFI) in PTC patients. Overexpression of LINC00924 significantly reduced cell proliferation, migration, and invasion, while augmenting apoptosis in PTC cells. Conclusion: Our findings highlight the potential of ICD-related lncRNAs as prognostic biomarkers for PFI in PTC. In vitro experiments suggest a protective role of LINC00924 in PTC progression.

Identifying Hub Genes and Immune Cell Infiltration for the Progression of Carotid Atherosclerotic Plaques in the Context of Predictive and Preventive Using Integrative Bioinformatics Approaches and Machine-Learning Strategies.

Emerging evidence shows that carotid atherosclerosis is related to the activation of immune-related pathways and inflammatory cell infiltration. However, the immune-linked pathways that helped in the advancement of the carotid atherosclerotic plaque and the association of such plaques with the infiltration status of the body's immune cells still unclear. Here, the expression profiles of the genes expressed during the progression of the carotid atherosclerotic plaques were retrieved from the Gene Expression Omnibus database and 178 differentially expressed genes were examined. The Weighted Gene Coexpression Network Analysis technique identified one of the brown modules showed the greatest correlation with carotid atherosclerotic plaques. In total, 66 intersecting genes could be detected after combining the DEGs. LASSO regression analysis was subsequently performed to obtain five hub genes as potential biomarkers for carotid atherosclerotic plaques. The functional analysis emphasized the vital roles played by the inflammation- and immune system-related pathways in this disease. The immune cell infiltration results highlighted the significant correlation among the CD4+ T cells, B cells, macrophages, and CD8+ T cells. Thereafter, the gene expression levels and the diagnostic values related to every hub gene were further validated. The above results indicated that macrophages, B cells, CD4+ T cells, and CD8 + T cells were closely related to the formation of the advanced-stage carotid atherosclerotic plaques. Based on the results, it could be hypothesized that the expression of hub genes (C3AR1, SLAMF8, TMEM176A, FERMT3, and GIMAP4) assisted in the advancement of the early-stage to advanced-stage carotid atherosclerotic plaque through immune-related signaling pathways. This may help to provide novel strategies for the treatment of carotid plaque in the context of predictive, preventive, and personalized medicine.

Atlas of circulating immune cells in Kawasaki disease.

Increasing evidence shows that the pathogenesis of Kawasaki disease (KD) is caused by abnormal and unbalanced innate and adaptive immune responses. However, the changes in and functions of adaptive immune cells in the peripheral blood of subjects with KD remain controversial. In this study, three different methods, CIBERSORT, Immune Cell Abundance Identifier (ImmuCellAI), and immune cell markers, were used to evaluate the proportions and abundances of immune cells in eight KD datasets (GSE9863, GSE9864, GSE18606, GSE63881, GSE68004, GSE73461, GSE73463, and GSE64486; a total of 1,251 samples). Compared with those in normal controls and convalescent KD samples, the proportions and abundances of innate immune cells such as neutrophils, monocytes, and macrophages in acute KD peripheral blood samples were significantly increased, while those of adaptive immune cells such as B and T cells were significantly decreased. The change tendencies of these immune cells were similar to those observed in other febrile illnesses but were more significant. However, in the coronary artery tissues of patients with convalescent KD, adaptive immune cells, especially B cells and CD8+ T cell subsets, were significantly increased. This result suggests that adaptive immune cells can be selectively recruited from peripheral blood into the coronary arteries. In addition, we found that elevated neutrophils in peripheral blood could be used as a biomarker to assist in the differential diagnosis of KD, but we did not find immune cells that could accurately predict intravenousimmunoglobulin (IVIG) responses in multiple datasets.

Analysis of the prognostic significance and potential mechanisms of lncRNAs associated with m6A methylation in papillary thyroid carcinoma.

BACKGROUND: m6A methylation-related long non-coding RNAs (lncRNAs) play a significant role in the progression of various tumors and can be used as prognostic markers. However, whether m6A-related lncRNAs also play the same function as prognostic markers in papillary thyroid carcinoma (PTC) remains unclear. METHODS: Consensus cluster analysis was performed to divide PTC samples obtained from The Cancer Genome Atlas database into two clusters according to the expression of m6A-related lncRNAs. Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to create and verify a prognostic model. Furthermore, the relationship among risk scores, clusters, programmed death-ligand 1 (PD-L1), tumor microenvironment (TME), clinicopathological characteristics, immune infiltration, immune checkpoint, and tumor mutation burden (TMB) was analyzed. In addition, a nomogram was created, and subsequently, the drug sensitivity of lncRNAs in the prognostic model was analyzed. Finally, the relationship between these lncRNAs and prognosis in pan-cancer was investigated. RESULTS: The prognosis, RAS, BRAF, M, and TME were found to be different in two clusters. The prognostic model included three lncRNAs: PSMG3-AS1, BHLHE40-AS1, and AC016747.3. The risk score was associated with clusters, PD-L1, tumor microenvironment, clinicopathological characteristics, immune cell infiltration, immune checkpoint, and TMB, and thus, risk score was confirmed as useful prognostic indicator. Differentially expressed lncRNAs are involved in many malignancies and can be identified as cancer prognostic makers. CONCLUSION: According to our research, we can regard m6A-related lncRNAs involved in the procession of PTC as a biomarker of progression-free survival for PTC patients, and pan-cancer.

Development and validation of a ferroptosis-related prognostic model for the prediction of progression-free survival and immune microenvironment in patients with papillary thyroid carcinoma.

BACKGROUND: Ferroptosis is an iron-dependent and regulated cell death that has been widely reported in a variety of malignancies. The overall survival of papillary thyroid cancer (PTC) is excellent, but the identification of patients with poor prognosis still faces challenges. Nevertheless, whether ferroptosis-related genes (FRGs) can be used to screen high-risk patients is not clear. METHODS: We obtained the clinical data of patients with PTC and FRGs from the UCSC Xena platform and the FerrDb respectively. Differentially expressed genes (DEGs) of FRGs were obtained from the entire The Cancer Genome Atlas (TCGA). Subsequently, the entire TCGA dataset was randomly split into two subsets: training and test datasets. Based on DEGs, we constructed a predictive model which was tested in the test dataset and the entire TCGA dataset to predict progression-free survival (PFS). Patients were categorized into high- or low-risk groups based on their median risk score. We analyzed differences in some aspects, including pathway enrichment analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), tumor microenvironment (TME), human leukocyte antigen (HLA) genes, and tumor mutation burden (TMB) analyses, between high-risk and low-risk groups. RESULTS: A predictive model with three FRGs (HSPA5, AURKA, and TSC22D3) was constructed. Patients in the high-risk group had worse PFS compared with patients in the low-risk group. Functional analysis results revealed that ssGSEA, immune cell infiltration, TME, HLA, and TMB were closely associated with ferroptosis. CONCLUSION: The prognostic model constructed in this study can effectively predict PFS for patients with PTC.