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Deep unrolling networks (DUNs) have emerged as a promising approach for solving compressed sensing (CS) problems due to their superior explainability, speed, and performance compared to classical deep network models. However, the CS performance in terms of efficiency and accuracy remains a principal challenge for approaching further improvements. In this paper, we propose a novel deep unrolling model, SALSA-Net, to solve the image CS problem. The network architecture of SALSA-Net is inspired by unrolling and truncating the split augmented Lagrangian shrinkage algorithm (SALSA) which is used to solve sparsity-induced CS reconstruction problems. SALSA-Net inherits the interpretability of the SALSA algorithm while incorporating the learning ability and fast reconstruction speed of deep neural networks. By converting the SALSA algorithm into a deep network structure, SALSA-Net consists of a gradient update module, a threshold denoising module, and an auxiliary update module. All parameters, including the shrinkage thresholds and gradient steps, are optimized through end-to-end learning and are subject to forward constraints to ensure faster convergence. Furthermore, we introduce learned sampling to replace traditional sampling methods so that the sampling matrix can better preserve the feature information of the original signal and improve sampling efficiency. Experimental results demonstrate that SALSA-Net achieves significant reconstruction performance compared to state-of-the-art methods while inheriting the advantages of explainable recovery and high speed from the DUNs paradigm.
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Algoritmos , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
BACKGROUND: The prognostic impact and clinicopathological characteristics of extracapsular lymph node involvement (ECLNI) in patients with surgically resected lung adenocarcinoma (LUAD) remain unknown in the context of the eighth edition N classification. PATIENTS AND METHODS: We retrospectively reviewed 279 patients with stage II-IIIA LUAD who underwent lobectomy and lymphadenectomy. The correlations of ECLNI presence and clinicopathological profiles were analyzed. We also assessed the impact of ECLNI on the postoperative survival of pN1 and pN2 LUAD patients. RESULTS: ECLNI-positive status was more common in patients with high lymph node yield and in patients with multiple stations involved. The logistic regression model identified tumor spread through air spaces, micropapillary component, cribriform component, and nodal stage as predictive factors for ECLNI presence. LUAD patients with ECLNI presence had an increased risk of locoregional recurrence compared with those without (p < 0.001). Presence of ECLNI was confirmed as an independent risk factor for worse recurrence-free survival (RFS) (p < 0.001) and overall survival (OS) (p < 0.001) in the entire cohort. Among the 61 patients with ECLNI(+)pN2 disease, our analysis revealed that adjuvant radiation was a significant predictor of improved RFS and OS. In addition, ECLNI status provides additional precision in stratifying pN1 and pN2 patients with significantly different RFS and OS. CONCLUSIONS: Our data suggest that ECLNI remains a strong prognosticator of unfavorable OS and RFS for LUADs in the context of the eighth edition N classification. Adjuvant radiation should be actively considered for pN1b and pN2 LUAD patients with ECLNI presence.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: This study sought to determine the optimal number of examined lymph nodes (ELNs) and examined node stations (ENSs) in patients with radiologically pure-solid non-small cell lung cancer (NSCLC) who underwent lobectomy and ipsilateral lymphadenectomy by investigating the impact of ELNs and ENSs on accurate staging and long-term survival. MATERIALS AND METHODS: Data from 6 institutions in China on resected clinical stage I-II (cI-II) NSCLCs presenting as pure-solid tumors were analyzed for the impact of ELNs and ENSs on nodal upstaging, stage migration, recurrence-free survival (RFS), and overall survival (OS). Correlations between different endpoints and ELNs or ENSs were fitted with a LOWESS smoother, and the structural break points were determined by Chow test. RESULTS: Both ELNs and ENSs were identified as independent prognostic factors for OS (ENS hazard ratio [HR], 0.690; 95% CI, 0.597-0.797; P<.001; ELN HR, 0.950; 95% CI, 0.917-0.983; P=.004) and RFS (ENS HR, 0.859; 95% CI, 0.793-0.931; P<.001; ELN HR, 0.960; 95% CI, 0.942-0.962; P<.001), which were also associated with postoperative nodal upstaging (ENS odds ratio [OR], 1.057; 95% CI, 1.002-1.187; P=.004; ELN OR, 1.186; 95% CI, 1.148-1.226; P<.001). A greater number of ELNs and ENSs correlated with a higher accuracy of nodal staging and a lower probability of stage migration. Cut-point analysis revealed an optimal cutoff of 18 LNs and 6 node stations for stage cI-II pure-solid NSCLCs, which were validated in our multi-institutional cohort. CONCLUSIONS: Extensive examination of LNs and node stations seemed crucial to predicting accurate staging and survival outcomes. A threshold of 18 LNs and 6 node stations might be considered for evaluating the quality of LN examination in patients with stage cI-II radiologically pure-solid NSCLCs.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Escisión del Ganglio Linfático , Carcinoma de Pulmón de Células no Pequeñas/cirugía , China , Humanos , Neoplasias Pulmonares/cirugía , Estadificación de NeoplasiasRESUMEN
C-N bond formation is regarded as a very useful and fundamental reaction for the synthesis of nitrogen-containing molecules in both organic and pharmaceutical chemistry. Noble-metal and homogeneous catalysts have frequently been used for C-N bond formation, however, these catalysts have a number of disadvantages, such as high cost, toxicity, and low atom economy. In this work, a low-toxic and cheap iron complex (iron ethylene-1,2-diamine) has been loaded onto carbon nanotubes (CNTs) to prepare a heterogeneous single-atom catalyst (SAC) named Fe-Nx /CNTs. We employed this SAC in the synthesis of C-N bonds for the first time. It was found that Fe-Nx /CNTs is an efficient catalyst for the synthesis of C-N bonds starting from aromatic amines and ketones. Its catalytic performance was excellent, giving yields of up to 96 %, six-fold higher than the yields obtained with noble-metal catalysts, such as AuCl3 /CNTs and RhCl3 /CNTs. The catalyst showed efficacy in the reactions of thirteen aromatic amine substrates, without the need for additives, and seventeen enaminones were obtained. High-angle annular dark-field scanning transmission electron microscopy in combination with X-ray absorption spectroscopy revealed that the iron species were well dispersed in the Fe-Nx /CNTs catalyst as single atoms and that Fe-Nx might be the catalytic active species. This Fe-Nx /CNTs catalyst has potential industrial applications as it could be cycled seven times without any significant loss of activity.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Quimioterapia Adyuvante , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Estadificación de NeoplasiasRESUMEN
To address the vibration problem induced by rotor eccentricity in a composite cage rotor bearingless induction motor(CCR-BIM), a vibration compensation control approach based on the fuzzy coefficient adaptive-linear-neuron is proposed. Firstly, the CCR-BIM mathematical model and the mechanism of unbalanced vibration are investigated, obtaining the expression of rotor displacement when the rotor is unbalanced. Afterwards, the displacement is decomposed by the fuzzy coefficient adaptive-linear-neuron algorithm to obtain the harmonic component related to vibration, and the value range of the weight coefficient is determined using stability analysis. Furthermore, through analyzing the shortcomings of the traditional PID vibration compensation method, a rotor vibration compensation method based on the fuzzy coefficient adaptive-linear-neuron is put forward to achieve high-performance vibration compensation control. Finally, the PID method and the proposed fuzzy coefficient adaptive-linear-neuron algorithm are simulated and verified by experiments. The findings demonstrate that the proposed algorithm successfully not only suppresses rotor unbalanced vibration but also exhibiting great dynamic performance.
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Cartilage tissue engineering offers hope for tracheal cartilage defect repair. Establishing an anti-inflammatory microenvironment stands as a prerequisite for successful tracheal cartilage restoration, especially in immunocompetent animals. Hence, scaffolds inducing an anti-inflammatory response before chondrogenesis are crucial for effectively addressing tracheal cartilage defects. Herein, we develop a shell-core structured PLGA@ICA-GT@KGN nanofilm using poly(lactic-co-glycolic acid) (PLGA) and icariin (ICA, an anti-inflammatory drug) as the shell layer and gelatin (GT) and kartogenin (KGN, a chondrogenic factor) as the core via coaxial electrospinning technology. The resultant PLGA@ICA-GT@KGN nanofilm exhibited a characteristic fibrous structure and demonstrated high biocompatibility. Notably, it showcased sustained release characteristics, releasing ICA within the initial 0 to 15 days and gradually releasing KGN between 11 and 29 days. Subsequent in vitro analysis revealed the potent anti-inflammatory capabilities of the released ICA from the shell layer, while the KGN released from the core layer effectively induced chondrogenic differentiation of bone marrow stem cells (BMSCs). Following this, the synthesized PLGA@ICA-GT@KGN nanofilms were loaded with BMSCs and stacked layer by layer, adhering to a 'sandwich model' to form a composite sandwich construct. This construct was then utilized to repair circular tracheal defects in a rabbit model. The sequential release of ICA and KGN facilitated by the PLGA@ICA-GT@KGN nanofilm established an anti-inflammatory microenvironment before initiating chondrogenic induction, leading to effective tracheal cartilage restoration. This study underscores the significance of shell-core structured nanofilms in temporally regulating anti-inflammation and chondrogenesis. This approach offers a novel perspective for addressing tracheal cartilage defects, potentially revolutionizing their treatment methodologies.
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AIMS: Conflicting data were provided regarding the prognostic impact and genomic features of lung adenocarcinoma (LUAD) with lepidic growth pattern (LP+A). Delineation of the genomic and immune characteristics of LP+A could provide deeper insights into its prognostic implications and treatment determination. METHODS: We conducted a search of articles in PubMed, EMBASE and the Cochrane Library from inception to January 2024. A domestic cohort consisting of 52 LUAD samples was subjected to whole-exome sequencing as internal validation. Data from The Cancer Genomic Atlas and the Gene Expression Omnibus datasets were obtained to characterise the genomic and immune profiles of LP+A. Pooled HRs and rates were calculated. RESULTS: The pooled results indicated that lepidic growth pattern was either predominant (0.35, 95% CI 0.22 to 0.56, p<0.01) or minor (HR 0.50, 95% CI 0.36 to 0.70, p<0.01) histological subtype was associated with favourable disease-free survival. Pooled gene mutation rates suggested higher EGFR mutation (0.55, 95% CI 0.46 to 0.64, p<0.01) and lower KRAS mutation (0.14, 95% CI 0.02 to 0.25, p=0.02) in lepidic-predominant LUAD. Lepidic-predominant LUAD had lower tumour mutation burden and pooled positive rate of PD-L1 expression compared with other subtypes. LP+A was characterised by abundance in resting CD4+memory T cells, monocytes and γδ T cells, as well as scarcity of cancer-associated fibroblasts. CONCLUSIONS: LP+A was a unique histological subtype with a higher EGFR mutation rate, lower tumour mutation burden and immune checkpoint expression levels. Our findings suggested potential benefits from targeted therapy over immunotherapy in LP+A.
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BACKGROUND: GTPase immunity-associated protein 7 (GIMAP7) has been previously recognized as a prognostic marker in pan-cancer. Our objective was to explore the function of GIMAP7 in the progression of lung adenocarcinoma (LUAD). METHODS: GIMAP7 was overexpressed by transfection with GIMAP7 plasmid, and knocked down using siRNAs. The biological functions of GIMAP7 were examined by employing CCK-8, EdU, colony formation, flow cytometry, wound healing, and transwell assays. The effects of GIMAP7 on the extracellular acidification rate (ECAR), oxygen consumption rate (OCR), lactate production, and glucose uptake were evaluated. In addition, the related mRNA and protein expression was detected employing immunohistochemical, western blot, and qRT-PCR. A xenograft tumor model was established in nude mice to evaluate the effects of GIMAP7 on tumor growth. RESULTS: GIMAP7 was lowly expressed in LUAD tissues and cells. GIMAP7 inhibited the proliferation, mobility, EMT, glycolysis, but promoted apoptosis in LUAD cells. Moreover, we also confirmed that GIMAP7 suppressed Smo/AMPK signaling in LUAD cells. By adding the Smo agonist SAG and AMPK agonist GSK621, the results of rescue experiments further verified that GIMAP7 played a role in LUAD inhibition through inhibition of the Smo/AMPK signaling pathway. Furthermore, the role of GIMAP7 in inhibiting tumor growth was verified in vivo. CONCLUSIONS: These results demonstrate that GIMAP7 could inhibit cell proliferation, mobility and glycolysis, but accelerate apoptosis via repressing the Smo/AMPK signaling pathway in LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Animales , Ratones , Humanos , GTP Fosfohidrolasas , Proteínas Quinasas Activadas por AMP , Ratones Desnudos , Transducción de Señal , Transición Epitelial-Mesenquimal , Adenocarcinoma del Pulmón/genética , Glucólisis , Proliferación Celular , Modelos Animales de Enfermedad , Neoplasias Pulmonares/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al GTPRESUMEN
Background: It remains undetermined whether preoperative computed tomography (CT)-guided hookwire localization would result in elevated risk of tumor spread through air spaces (STAS) in stage IA lung adenocarcinoma. Methods: A total of 1836 patients who underwent lobectomy were included. To eliminate the potential impact of confounding factors on producing STAS, propensity score-matching (PSM) was used to create two balanced subgroups stratified by implementation of hookwire localization. We also introduced an external cohort including 1486 patients to explore the effect of hookwire localization on the incidence of STAS and patient survival after sublobar resection (SR). For proactive simulation of hookwire localization, 20 consecutive lobectomy specimens of p-stage IA lung adenocarcinoma were selected. Results: Ex vivo tests revealed that mechanical artifacts presenting as spreading through a localizer surface (STALS) could be induced by hookwire localization but be distinguished by CD68 and AE1/3 antibody-based immunohistochemistry. The distance of STALS dissemination tended to be shorter compared with real STAS (P = 0.000). After PSM, implementation of hookwire localization was not associated with elevated STAS incidence, nor worse survival in p-stage IA patients undergoing lobectomy irrespective of STAS. Conclusions: CT-guided hookwire localization might induce mechanical artifacts presenting as STALS which could be distinguished by immunohistochemistry, but would not affect survival in p-stage IA disease. Surgeons can be less apprehensive about performing hookwire localization in relation to STAS on stage IA disease suitable for SR.
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OBJECTIVES: This study aimed to investigate the potential of complex glandular patterns (CGP) in lymph node micrometastasis (LNMM) and to determine the clinical beneficiaries in stage I lung adenocarcinoma (LUAD) with CGP. Meanwhile, the feasibility of detecting CGP on frozen section was also evaluated. METHODS: We retrospectively analysed the clinicopathological characteristics of 848 pathologic-stage I LUADs. A logistic regression model and a Cox proportional-hazards model were conducted to define the risk factors for LNMM and survival respectively. Furthermore, 5 pathologists reviewed frozen sections of 100 LUADs independently. RESULTS: The logistic regression model indicated that CGP [odds ratio 3.89, 95% confidence interval (CI) 2.46-6.15; P < 0.001] was an independent predictor of the presence of LNMM. Subgroup analysis revealed that CGP-present/LNMM-positive LUAD had the highest risk of both loco-regional and distant recurrence. Moreover, adequate lymphadenectomy [recurrence-free survival: hazard ratio (HR) 0.61, 95% CI 0.40-0.95; P = 0.028; overall survival: HR 0.64, 95% CI 0.41-0.99; P = 0.043] and adjuvant chemotherapy (recurrence-free survival: HR 0.30, 95% CI 0.18-0.52; P < 0.001; overall survival: HR 0.33, 95% CI 0.19-0.57; P < 0.001) brought survival benefits to CGP-present patients, especially to CGP-present/LNMM-positive subgroup. Across the 5 pathologists, sensitivity ranged from 59 to 68% and specificity ranged from 79 to 83%, with moderate diagnostic agreement and high interobserver agreement for detecting CGP on frozen section. CONCLUSIONS: LNMM was more frequently observed in stage I LUAD with CGP. Adequate lymphadenectomy and adjuvant chemotherapy were associated with improved survival in CGP-present patients, especially in CGP-present/LNMM-positive subgroup. Additionally, it is feasible to identify CGP on frozen section intraoperatively.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Pronóstico , Estudios Retrospectivos , Metástasis Linfática , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/patología , Micrometástasis de Neoplasia/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Estadificación de NeoplasiasRESUMEN
BACKGROUND: T cell factor-1 (TCF-1) + stem-like tumor-infiltrating lymphocytes (stem-like TILs) are important memory cells in the tumor microenvironment. However, their relationship with clinicopathological features, CD8+ TIL densities, immune checkpoint inhibitors (ICs), and prognostic values remain unknown for lung adenocarcinomas (LUADs). In this study, we aimed to characterize TCF-1+ TILs and their prognostic significance in patients with surgically resected LUADs. METHODS: Expression of TCF-1, CD8, and ICs including programmed death-1 (PD-1), lymphocyte activating-3 (LAG-3), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3) in TILs were estimated using immunohistochemistry of resected LUADs. The association between TCF-1 expressions and clinicopathological characteristics of patient prognoses were analyzed. RESULTS: Positive TCF-1 expression significantly correlated with advanced pathological stage, tumor grade, CD8+ TILs density, TIM-3 expression, LAG-3 expression, and PD-1 expression. TCF-1 positivity was significantly associated with a better recurrence-free survival (RFS), and overall survival (OS). Subgroup analysis revealed that the TCF-1+/CD8+ group had the best RFS and OS, while the TCF-1-/CD8- group had the worst RFS and OS. Similarly, patients with TCF-1 + PD-1- had the best prognoses and patients with TCF-1-PD-1+ had the worst prognoses. CONCLUSION: TCF-1 had relatively high positive expression and special clinicopathological features in patients with LUAD. TCF-1+ TILs were related to CD8 density, TIM-3 expression, LAG-3 expression, and PD-1 expression, and were associated with better prognoses in LUAD patients. A combination of TCF-1 and CD8 densities or PD-1 expression further stratified patients into different groups with distinct prognoses.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A , Neoplasias Pulmonares/patología , Pronóstico , Receptor de Muerte Celular Programada 1/metabolismo , Microambiente TumoralRESUMEN
AIMS: We investigated the clinical implications and molecular features of TLS in stage I lung adenocarcinoma (LUAD). METHODS: We retrospectively reviewed the clinicopathological characteristics of 540 patients with p-stage I LUAD. Logistic regression analysis was applied to determining the relationships between clinicopathological features and the presence of TLS. TLS-associated immune infiltration pattern and signature genes were characterized using the transcriptomic profiles of 511 LUADs from The Cancer Genome Atlas (TCGA) database. RESULTS: The presence of TLS was associated with a higher pT stage, low- and middle-grade patterns, and the absence of tumor spreading through air spaces (STAS) and subsolid nodules. Multivariate Cox regression analysis identified that the presence of TLS was associated with favorable overall survival (OS) (p < 0.001) and recurrence-free survival (RFS) (p < 0.001). Subgroup analysis showed that the most favorable OS (p < 0.001) and RFS (p < 0.001) favored the TLS + PD-1- subgroup. The presence of TLS was characterized by abundance in antitumor immunocytes including activated CD8+ T and B cells as well as dentritic cells in TCGA cohort. CONCLUSION: The presence of TLS was an independent favorable factor for patients with stage I LUAD. The presence TLS was featured by special immune profiles which might aid oncologists in determining personalized adjuvant treatment.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Estructuras Linfoides Terciarias , Humanos , Estudios Retrospectivos , Estructuras Linfoides Terciarias/patología , Pronóstico , Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/patologíaRESUMEN
To realize the low-cost and high-performance of a bearingless induction motor (BIM), a speed sensorless control strategy combined with the improved sliding mode observer (SMO) and phase locked-loop (PLL) is proposed. Based on analyzing the principle of the traditional SMO, the improved SMO adopts a switching function that has a double boundary layer structure to reduce the high-frequency jitter. Firstly, the observation equation of the rotor flux is established where the stator current, as well as the rotor flux are two state variables, and then the system stability is discussed with the Lyapunov theory. Secondly, to reduce the rotor chatter and enhance the speed tracking performance a flux electrical angle detecting module is constructed based on the PLL structure that extracts the rotor flux electrical angle and speed from the observed flux component. Finally, the BIM speed sensorless vector control system is established and the simulation results and experimental results are respectively presented by the MATLAB/Simulink simulation platform and a laboratory prototype. Both results prove that this strategy can not only enhance the speed self-detection capability and tracking performance, but can guarantee the excellent self-suspension function as well.
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Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and one of the main causes of cancer-related deaths. In the past decade, with the widespread use of computed tomography (CT) in routine screening for lung cancer, the incidence of LUAD presenting as small pulmonary nodules radiologically, has increased remarkably. The mechanisms of the occurrence and progression of LUADs are complex, and the prognoses of patients with LUAD vary significantly. Although significant progress has been made in targeted therapy and immunotherapy for LUADs in recent years, the drug resistance of tumor cells has not been effectively overcome, which limits the benefits of patients. With the accomplishment of the Human Genome Project, sequencing-based genomic and transcriptomics have come into the field of clinical and scientific researches. Single-cell sequencing, as a new type of sequencing method that has captured increasing attention recently, can perform specific analysis of cell populations at single-cell level, which can reveal the unique changes of each cell type. Single-cell sequencing can also provide accurate assessment on heterogeneous stromal cells and cancer cells, which is helpful to reveal the complexity of molecular compositions and differences between non- and malignant tissues. To sum up, it is an urgent need for clinicians and basic scientists to deeply understand the pathogenesis and development of LUAD, the heterogeneity of tumor microenvironment (TME) and the mechanism of drug resistance formation through single-cell sequencing, so as to discover new therapeutic targets. In this paper, we reviewed and summarized the application and progress in single-cell sequencing of LUADs.â©.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Análisis de Secuencia de ARN , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/fisiopatología , Resistencia a Antineoplásicos/fisiología , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/fisiopatología , Pronóstico , Análisis de Secuencia de ARN/métodos , Análisis de Secuencia de ARN/tendencias , Microambiente Tumoral/fisiologíaRESUMEN
OBJECTIVES: CD66b positive tumor-infiltrating neutrophils (TINs) are key immunity cells in the tumor microenvironment (TME). However, their relationship with clinicopathological features, immune checkpoints (ICs), and prognostic value remains undetermined in lung adenocarcinoma (LUAD). In this study, we aimed to characterize the infiltration by TINs and the prognostic significance in patients with surgically resected LUAD. MATERIALS AND METHODS: Expression of CD66b and ICs, including PD-L1, PD-1, CTLA4, LAG3, TIM3, TIGIT, VISTA, and BTLA, in both cancer cell and tumor-infiltrating lymphocytes (TILs) were estimated by immunohistochemistry in resected LUAD. The associations between CD66b expression and clinicopathological characteristics in patient prognoses were analyzed. We also verified results in another cohort from 85 patients with untreated LUAD and further analyzed the correlation between CD66b expression and EGFR and KRAS mutation status in addition to the rearrangement of the anaplastic lymphoma receptor tyrosine kinase gene (ALK). RESULTS: A total of 240 patients were included in this study. CD66b expression was observed in 87 (36.2%) samples. ICs including PD-L1, PD-1, CTLA4, LAG3, TIM3, TIGIT, VISTA, and BTLA were observed in percentages that ranged from 23.8% to 59.4%. Positive CD66b expression significantly correlated with smoking history (p = 0.029), pathological stage (p = 0.040), and the positive expression of LAG-3 (p < 0.001), PD-1 (p = 0.008), CTLA-4 (p = 0.013), TIM-3 (p = 0.025), TIGIT (p = 0.002), PD-L1 in TILs (p = 0.015), and PD-L1 in tumor cells (p = 0.010). CD66b positivity was significantly associated with worse recurrence-free survival (RFS) (hazard ratio, HR, 1.687; 95% confidence interval, CI, 1.058-2.690, p = 0.028) and overall survival (OS) (HR, 1.667; 95% CI, 1.097-2.534, p = 0.017). Subgroup analysis revealed that the CD66b+/LAG-3 + group had the worst RFS (5-year rate: 39.5%,) and OS (5-year rate: 53.7%,), while the CD66b-/LAG-3 - group had the best RFS (5-year rate: 65.6%) and OS (5-year rate: 78.8%). The p value in analysis of RFS and OS was 0.005 and 0.008, respectively. In the verification set, high expression of CD66b was also significantly correlated with the positive expression of LAG-3 (p < 0.001), PD-1 (p = 0.002), CTLA-4 (p = 0.034), TIM-3 (p = 0.049), PD-L1 in TILs (p = 0.003), and PD-L1 in tumor cells (p = 0.045). There was no correlation between CD66b expression and positive TIGIT expression (p = 0.077), EGFR mutation (p = 0.223), KRAS mutation (p = 0.151), and ALK fusion (p = 0.310). CONCLUSION: CD66b had a relatively high positive expression rate and special clinicopathological features in patients with LUAD. CD66b + TINs were related to the expression of ICs and associated with poor prognoses in LUAD. A combination of CD66b and ICs, especially LAG-3 could further stratify patients into different groups with distinct prognoses.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Procedimientos Quirúrgicos Pulmonares , Adenocarcinoma/genética , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Pronóstico , Microambiente TumoralRESUMEN
BACKGROUND AND OBJECTIVE: Increasing evidence has elucidated the clinicopathological significance of individual TME component in predicting outcomes and immunotherapeutic efficacy in lung adenocarcinoma (LUAD). Therefore, we aimed to investigate whether comprehensive TME-based signatures could predict patient survival and therapeutic responses in LUAD, and to assess the associations among TME signatures, single nucleotide variations and clinicopathological characteristics. METHODS: In this study, we comprehensively estimated the TME infiltration patterns of 493 LUAD patients and systematically correlated the TME phenotypes with genomic characteristics and clinicopathological features of LUADs using two proposed computational algorithms. A TMEscore was then developed based on the TME signature genes, and its prognostic value was validated in different datasets. Bioinformatics analysis was used to evaluate the efficacy of the TMEscore in predicting responses to immunotherapy and chemotherapy. RESULTS: Three TME subtypes were identified with no prognostic significance exhibited. Among them, naïve B cells accounted for the majority in TMEcluster1, while M2 TAMs and M0 TAMs took the largest proportion in TMEcluster2 and TMEcluster3, respectively. A total of 3395 DEGs among the three TME clusters were determined, among which 217 TME signature genes were identified. Interestingly, these signature genes were mainly involved in T cell activation, lymphocyte proliferation and mononuclear cell proliferation. With somatic variations and tumor mutation burden (TMB) of the LUAD samples characterized, a genomic landscape of the LUADs was thereby established to visualize the relationships among the TMEscore, mutation spectra and clinicopathological profiles. In addition, the TMEscore was identified as not only a prognosticator for long-term survival in different datasets, but also a predictive biomarker for the responses to immune checkpoint blockade (ICB) and chemotherapeutic agents. Furthermore, the TMEscore exhibited greater accuracy than other conventional biomarkers including TMB and microsatellite instability in predicting immunotherapeutic response (p < 0.001). CONCLUSION: In conclusion, our present study depicted a comprehensive landscape of the TME signatures in LUADs. Meanwhile, the TMEscore was proved to be a promising predictor of patient survival and therapeutic responses in LUADs, which might be helpful to the future administration of personalized adjuvant therapy.
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The morbidity of lung cancer ranks top in the world. At present, lung adenocarcinoma (LUAD) is the most common histologic type of lung cancer. However, the prognoses of LUAD patients with the same subtype remain heterogeneous. Histological heterogeneity is one of the main causes of diverse prognoses of patients with LUAD. Studies have shown that there are other histologic patterns that affect the clinical outcomes of LUAD patients, in addition to the five growth patterns of invasive LUAD classified by the World Health Organization (WHO) in 2015. The cribriform component (CC) is one of the research hotspots among histopathology of LUAD. Previous studies have shown that the presence of CC can further stratify the prognoses of patients with LUAD. Along with the progressively deep insights into the aforementioned topic, researchers are dedicating to unveiling the relationships among CC and and other clinicopathological factors as well as their joint influence on the survival of LUAD patients. The review manages to generalize the latest research progress in the CC in LUAD patients.
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Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/terapia , Humanos , PronósticoRESUMEN
The industrial waste coal combustion fly ash (CCFA) was used as a cheap catalyst support and by facile co-impregnation method, the active component Ni and promoter Re was loaded to form a bimetallic catalyst for high-performance CO2 methanation. The physico-chemical properties of the prepared catalyst were further measured by a series of characterizations such as X-ray fluorescence (XRF), N2 isothermal adsorption-desorption, X-ray diffraction (XRD), H2 temperature-programmed reduction (H2-TPR) et al. The effect of reaction temperature and gas hourly space velocity (GHSV) on the catalytic performance was carefully investigated on a continuous fixed-bed reactor. The results showed that in comparison with the non-promoted monometallic Ni/CCFA catalyst, the bimetallic Ni-Re/CCFA catalyst displayed a superior activity, which could achieve 99.55% of CO2 conversion and 70.27% of CH4 selectivity under the condition of 400 °C, 2000 h-1, 1 atm and H2:CO2:N2 = 4:1:0.5, possibly owing to the higher Ni dispersion and more active sites in Ni-Re/CCFA. Besides, the addition of Re promoter was beneficial to enhance the catalyst anti-sintering and anti-coking abilities as reflected by the smaller Ni particle size growth and less carbon deposition amount in Ni-Re/CCFA. The in-situ diffuse reflection infrared Fourier transform spectrum (in-situ DRIFTS) was finally carried out to determine the CO2 adsorption state and its methanation intermediates, from which a loop mechanism of CO2 methanation process was proposed and depicted.