Expression and Clinical Significance of MAGE-A Proteins and mRNA in Lung Cancer Patients: A Retrospective Study.

Objective: This study investigated the expression and clinical significance of Melanoma Associated Antigen (MAGE)-A proteins and mRNA in patients with non-small cell lung cancer (NSCLC). Methods: A retrospective study was conducted, and we selected a cohort of 88 NSCLC patients treated at our hospital from January 2015 to January 2020. Adjacent tissues were chosen as controls. The expression of MAGE-A proteins in lung cancer and adjacent tissues was assessed via Western blot, while MAGE-As mRNA expression was measured using RT-PCR. Results: The relative expression levels of MAGE-A proteins and mRNA in NSCLC tissues were significantly higher than those in adjacent tissues (P < .05), with values of (0.343 ± 0.101) and (0.728 ± 0.112), respectively. Furthermore, MAGE-As protein expression was significantly higher in stage III - IV lung cancer compared to stage I - II (P < .05). No significant differences were observed in MAGE-A protein expression concerning gender, age, tumor diameter, pathological type, and differentiation degree (P > .05). The relative expression of MAGE-As mRNA was significantly higher in clinical stage III - IV and moderately differentiated lung cancer tissues compared to stage I - II and well-differentiated tissues (P < .05). No significant differences were found in MAGE-As mRNA expression concerning gender, age, tumor diameter, and pathological type (P > .05). Patients with high MAGE-As mRNA expression had a significantly shorter median overall survival of 33 months (95% CI: 31.64-34.36) compared to those with low MAGE-As mRNA expression (P < .05). However, no significant difference was observed in median overall survival between patients with high and low MAGE-As protein expression (P > .05). Conclusions: In NSCLC, the up-regulation of MAGE-A proteins and mRNA is associated with clinical stage and differentiation degree, warranting further investigation.

Predictive Value of EGFR Mutation Status for First-Line Tyrosine Kinase Inhibitor Treatment in Patients with Advanced Lung Cancer.

Objective: This study aims to investigate and analyze the correlation between EGFR-TKI first-line therapy and EGFR mutation status in patients with advanced lung cancer. Methods: We selected 60 patients with advanced lung cancer and EGFR mutations (diagnosed as stage IIIb or IV) from our hospital between January 2019 and November 2022. Each patient underwent an EGFR mutation test and was categorized into two groups based on their mutation status: 28 patients with exon 21 mutations and 32 with exon 19 deletions. After three months of therapy, we assessed treatment efficacy and adverse reactions. Results: Our data revealed that in the EGFR exon 21 mutation group, the objective response rate (ORR) and disease control rate (DCR) were 57.14% and 60.71%, respectively. In the EGFR exon 19 deletion group, the ORR and DCR were 68.75% and 84.38%, respectively. There were significant differences in DCR and ORR between the two EGFR mutation states, with statistical significance (P < .05). The progression-free survival (PFS) in the EGFR exon 21 mutant group was 8.4 months after third-generation EGFR-TKI treatment, while the EGFR exon 19 deletion group had a PFS of 12.7 months after the same treatment, with a statistically significant difference (P < .05). Cox regression analysis showed that female patients with no smoking history and an adenocarcinoma pathological type had significantly better PFS after treatment compared to male patients with a smoking history and squamous cell carcinoma type, with statistical significance (P < .05). Age and clinical stage did not significantly impact PFS after third-generation EGFR-TKI treatment (P > .05). Adverse reaction incidences, such as nausea, fatigue, diarrhea, vomiting, and rash, did not significantly differ in either the EGFR exon 21 mutation group or the EGFR exon 19 deletion group (P > .05). Conclusion: The status of EGFR mutations serves as a predictive factor for PFS, DCR, and ORR in lung cancer patients undergoing EGFR-TKI first-line therapy. This status can be a valuable predictive indicator of lung cancer treatment efficacy, with potential applications in clinical practice.

L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome.

Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer.

Purpose: Chromosomal abnormalities represent genomic signatures linked to cancer prognosis and responses to chemotherapy, immunotherapy, and drug resistance. This study aimed to investigate the impact of chromosome copy number variants (CNVs) on the efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC) patients, as well as its prognostic implications for progression-free survival (PFS) and overall survival (OS) in EGFR wild-type patients. Methods: A total of 110 patients with advanced NSCLC were enrolled in this study and categorized into EGFR-mutated and wild-type groups. Utilizing next-generation sequencing (NGS) technology, we assessed 24 genes and chromosome CNVs associated with lung cancer pathways in patients' tissue samples. Results: Within the EGFR-mutated group, patients with a gain in Chr 1p13.3-p13.1 exhibited poor TKI responses, a high relapse rate, and shortened PFS (P = 0.002). Conversely, EGFR-mutated patients with a gain in 14q31.1-q31.3 demonstrated favorable TKI responses and relatively extended PFS (P = 0.005). Among EGFR wild-type patients, the presence of 7q31.1-q31.31 CNV emerged as an independent factor influencing both PFS and OS (P = 0.013, P = 0.004). Notably, patients with a gain in 7q31.1-q31.31 exhibited prolonged PFS and OS. Additionally, independent prognostic significance for OS in EGFR wild-type patients was observed for CNVs in 9q21.31-q22.2 and 11p11.11-q12.1 regions (P = 0.001). Patients with gains in these regions experienced extended OS, while losses were predictive of poorer outcomes. Conclusion: Our results suggested that chromosomal copy number variation is a practical indicator for predicting the response of EGFR-targeted therapy and prognosis for NSCLC patients.

Long-Chain Branched Bio-Based Poly(butylene dodecanedioate) Copolyester Using Pentaerythritol as Branching Agent: Synthesis, Thermo-Mechanical, and Rheological Properties.

The introduction of long-chain branched structures into biodegradable polyesters can effectively improve the melt strength and blow-molding properties of polyesters. In this study, pentaerythritol (PER) was used as a branching agent to synthesize branched poly(butylene dodecanedioate) (PBD), and the resulting polymers were characterized by Nuclear Magnetic Resonance Proton Spectra (1H NMR) and Fourier Transform Infrared spectroscopy (FT-IR). It was found that the introduction of a small amount of PER (0.25-0.5 mol%) can generate branching and even crosslinking structures. Both impact strength and tensile modulus can be greatly improved by the introduction of a branching agent. With the introduction of 1 mol% PER content in PBD, the notched impact strength of PBD has been increased by 85%, and the tensile modulus has been increased by 206%. Wide-angle X-ray diffraction and differential scanning calorimetry results showed that PER-branched PBDs exhibited improved crystallization ability compared with linear PBDs. Dynamic viscoelastics revealed that shear-thickening behaviors can be found for all branched PBD under low shear rates.

Corrigendum: Advanced NSCLC patients with EGFR T790M harbouring TP53 R273C or KRAS G12V cannot benefit from osimertinib based on a clinical multicentre study by tissue and liquid biopsy.

[This corrects the article DOI: 10.3389/fonc.2021.621992.].

Effect of PTGES3 on the Prognosis and Immune Regulation in Lung Adenocarcinoma.

Background: PTGES3 is upregulated in multiple cancer types and promotes tumorigenesis and progression. However, the clinical outcome and immune regulation of PTGES3 in lung adenocarcinoma (LUAD) are not fully understood. This study aimed to explore the expression level and prognostic value of PTGES3 and its correlation with potential immunotherapy in LUAD. Methods: All data were obtained from several databases, including the Cancer Genome Atlas database. Firstly, gene and protein expression of PTGES3 were analyzed using Tumor Immune Estimation Resource (TIMER), R software, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA). Thereafter, survival analysis was conducted using the R software, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and Kaplan-Meier Plotter. In addition, gene alteration and mutation analyses were conducted using the cBio Cancer Genomics Portal (cBioPortal) and Catalog of Somatic Mutations in Cancer (COSMIC) databases. The molecular mechanisms associated with PTGES3 were assessed via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), GeneMANIA, GEPIA2, and R software. Lastly, the role of PTGES3 in immune regulation in LUAD was investigated using TIMER, Tumor-Immune System Interaction Database (TISIDB), and SangerBox. Results: The gene and protein expression of PTGES3 were elevated in LUAD tissues and compared to the normal tissues, and the high expression of PTGES3 was correlated with cancer stage and tumor grade. Survival analysis revealed that overexpression of PTGES3 was associated with poor prognosis of LUAD patients. Moreover, gene alteration and mutation analysis revealed the occurrence of several types of PTGES3 gene alterations in LUAD. Moreover, co-expression analysis and cross-analysis revealed that three genes, including CACYBP, HNRNPC, and TCP1, were correlated and interacted with PTGES3. Functional analysis of these genes revealed that PTGES3 was primarily enriched in oocyte meiosis, progesterone-mediated oocyte maturation, and arachidonic acid metabolism pathways. Furthermore, we found that PTGES3 participated in a complex immune regulation network in LUAD. Conclusion: The current study indicated the crucial role of PTGES3 in LUAD prognosis and immune regulation. Altogether, our results suggested that PTGES3 could serve as a promising therapeutic and prognosis biomarker for the LUAD.

L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome.

Synthesis of Biodegradable Polyester-Polyether with Enhanced Hydrophilicity, Thermal Stability, Toughness, and Degradation Rate.

Novel poly(butylene succinate-butylene furandicarboxylate/polyethylene glycol succinate) (PBSF-PEG) was synthesized using two-step transesterification and polycondensation in the melt. There are characterized by intrinsic viscosity, GPC, 1H NMR, DSC, TGA, tensile, water absorption tests, and water degradation at different pH. GPC analysis showed that PBSF-PEG had high molecular weight with average molecular weight (Mw) up to 13.68 × 104 g/mol. Tensile tests showed that these polymers possessed good mechanical properties with a tensile strength as high as 30 MPa and elongation at break reaching 1500%. It should be noted that the increase of PEG units improved the toughness of the polyester material. In addition, the introduction of PEG promoted the water degradation properties of PBSF, and the copolymer showed a significantly faster water degradation rate when the PEG unit content was 20%. This suggests that the amount of PEG introduced could be applied to regulate the water degradation rate of the copolymers. Hence, these new polymers have great potential for application as environmentally friendly and sustainable plastic packaging materials.

Comparison of operation time, efficacy and safety between through-the-scope stent and over-the-while stent in malignant central airway obstruction: a multi-center randomized control trial.

Background: Self-expandable metallic (SEM) airway stents are an important approach to treating malignant central airway obstruction (CAO). Standard over-the-while (OTW) stent needs the guidance of a guide-wire. It should be implanted under flouroscopy or the guidance of bronchoscope visualization. In this study, we evaluated the operation time and safety between OTW stent and a novel through-the-scope (TTS) SEM airway stent. Methods: In this multi-center, randomized, parallel-group superiority study, malignant CAO patients were enrolled randomly assigned (2:1) to the TTS stent implantation group (TTS group) or the standard OTW stent group (OTW group) in six sites across China. The entire process of all surgical procedures was recorded by video. Primary endpoint was the operation time of the airway stent implantation and secondary endpoint was the success rate of the stent implantation as well as its efficacy and safety. Results: From May 15, 2017, to December 30, 2018, 148 patients were enrolled from the six sites. We analyzed 134 patients (including 91 patients from the TTS group and 43 patients from the OTW group) according to the per-protocol set. There were no significant differences in the ages, genders, underlying diseases, and stenosis sites between the two groups. The operation time in the TTS group was significantly shorter than that in the OTW group (104±68 vs. 252±111 seconds, P<0.001). Compared to the OTW group, the efficacy of stent implantation (97.80% vs. 90.70%, P=0.093) and rate of first-time successful stent implantation (78.02% vs. 74.42%, P=0.668) were higher in the TTS group, but did not reach statistically significance. The rates of granulation (28.57% vs. 41.86%, P=0.128) and restenosis (15.38% vs. 30.23%, P=0.064) in the TTS group were slightly lower as compared with the OTW group without achieving statistical significance. Conclusions: The TTS stent implantation procedure time was significantly shorter than that of the OTW airway stent with similar efficacy and complications, which might reduce the risk and flexibility of stent implantation. Trial Registration: Chinese Clinical Trial Registry ChiCTR-IOR-17011431.

Clinical Study of Airway Stent Implantation in the Treatment of Patients with Malignant Central Airway Obstruction.

Background: Airway stenting is a therapeutic option for malignant central airway obstructions (MCAO), including both intraluminal and extraluminal obstructions. The objective of this study is to investigate the clinical features and results of long-term improved prognosis for MCAO patients after airway stent implantation. Methods: Ninety-eight MCAO patients who underwent stent placement in our hospital from January 2013 to April 2020 were included in this study. The data included baseline data, clinical characteristics, laboratory test data, stent implantation data, and treatment as well as survival after stent implantation. The survival rates among individuals were compared via log-rank tests. Potential prognostic factors were identified using multivariate cox hazard regression models. Results: A retrospective analysis of these patients was generated. MCAO was mainly caused by lung cancer (53/98, 54.08%), esophageal cancer (22/98, 22.45%), and thyroid cancer (3/98, 3.06%). The median survival time of participants was 5.5 months. Univariate analysis indicated that the survival rate was related to primary disease, ECOG PS score, stent site, hemoglobin (Hb), albumin (ALB), and serum lactate dehydrogenase (LDH) (P < 0.05). The cox risk regression model showed that the survival rate was significantly influenced by ECOG PS score (OR = 3.468, 95%CI = 1.426-8.432, P = 0.006) and stent site (OR = 1.544, 95%CI = 1.057-2.255, P = 0.025). Conclusions: Compared with the site of stent placement, the ECOG PS score is the primary factor in the survival rate of MCAO patients after airway stenting.

Improving Suspected Pulmonary Infection Diagnosis by Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing: a Multicenter Retrospective Study.

Metagenomic next-generation sequencing (mNGS) has been gradually applied to clinical practice due to its unbiased characteristics of pathogen detection. However, its diagnostic performance and clinical value in suspected pulmonary infection need to be evaluated. We systematically reviewed the clinical data of 246 patients with suspected pulmonary infection from 4 medical institutions between January 2019 and September 2021. The diagnostic performances of mNGS and conventional testing (CT) were systematically analyzed based on bronchoalveolar lavage fluid (BALF). The impacts of mNGS and CT on diagnosis modification and treatment adjustment were also assessed. The positive rates of mNGS and CT were 47.97% and 23.17%, respectively. The sensitivity of mNGS was significantly higher than that of CT (53.49% versus 23.26%, P < 0.01), especially for infections of Mycobacterium tuberculosis (67.86% versus 17.86%, P < 0.01), atypical pathogens (100.00% versus 7.14%, P < 0.01), viruses (92.31% versus 7.69%, P < 0.01), and fungi (78.57% versus 39.29%, P < 0.01). The specificity of mNGS was superior to that of CT, with no statistical difference (90.32% versus 77.42%, P = 0.167). The positive predictive value (PPV) and negative predictive value (NPV) of mNGS were 97.46% and 21.88%, respectively. Diagnosis modification and treatment adjustment were conducted in 32 (32/246, 13.01%) and 23 (23/246, 9.35%) cases, respectively, according to mNGS results only. mNGS significantly improved the diagnosis of suspected pulmonary infection, especially infections of M. tuberculosis, atypical pathogens, viruses, and fungi, and it demonstrated the pathogen distribution of pulmonary infections. It is expected to be a promising microbiological detection and diagnostic method in clinical practice. IMPORTANCE Pulmonary infection is a heterogeneous and complex infectious disease with high morbidity and mortality worldwide. In clinical practice, a considerable proportion of the etiology of pulmonary infection is unclear, microbiological diagnosis being challenging. Metagenomic next-generation sequencing detects all nucleic acids in a sample in an unbiased manner, revealing the microbial community environment and organisms and improving the microbiological detection and diagnosis of infectious diseases in clinical settings. This study is the first multicenter, large-scale retrospective study based entirely on BALF for pathogen detection by mNGS, and it demonstrated the superior performance of mNGS for microbiological detection and diagnosis of suspected pulmonary infection, especially in infections of Mycobacterium tuberculosis, atypical pathogens, viruses, and fungi. It also demonstrated the pathogen distribution of pulmonary infections in the real world, guiding targeted treatment and improving clinical management and prognoses.

A Non-Isocyanate Route to Poly(Ether Urethane): Synthesis and Effect of Chemical Structures of Hard Segment.

A series of non-isocyanate poly(ether urethane) (PEU) were prepared by an environmentally friendly route based on dimethyl carbonate, diols and a polyether. The effect of the chemical structure of polyurethane hard segments on the properties of this kind of PEU was systematically investigated in this work. Polyurethane hard segments with different structures were first prepared from hexamethylene di-carbamate (BHC) and different diols (butanediol, hexanediol, octanediol and decanediol). Subsequently, a series of non-isocyanate PEU were obtained by polycondensation of the polyurethane hard segments with the polyether soft segments (PTMG2000). The PEU were characterized by GPC, FT-IR, 1H NMR, DSC, WAXD, SAXS, AFM and tensile testing. The results show that the urea groups generated by the side reaction affect the degree of crystallization of hard segments by influencing the hydrogen bonding of the hard segments molecular chains. The degree of hard segment crystallization, in turn, affects the thermal and mechanical properties of the polymer. The urea group content is related to the carbon chain length of the diol used for the synthesis of hard segments. When butanediol is applied to synthesize hard segment, the hard segment of the resulting PEU is unable to crystallize. Therefore, the tensile strength and modulus of elasticity of butanediol-based PEU is lowest among three, though it possesses the highest urea group content. When longer octanediol or decanediol is applied to synthesize the hard segment, the hard segments in the resulting polyether-based polyurethane are crystallizable and the resulting PEU possesses higher tensile strength.

Expression of Serum sLOX-1 in Patients with Non-Small-Cell Lung Cancer and Its Correlation with Lipid Metabolism.

Objective: The aim of this study was to investigate the expression level of soluble LOX-1 (sLOX-1) in the serum of non-small-cell lung cancer (NSCLC) patients and its correlation with lipid metabolism. Methods: 99 inpatients with NSCLC and 81 healthy controls were enrolled in this study. The levels of serum sLOX-1 were compared between the two groups, and the correlation of sLOX-1 with clinicopathological characteristics, blood lipid indices, and carcinoembryonic antigen was analyzed. Results: Compared with the healthy controls, sLOX-1, low-density lipoprotein, triglyceride, and carcinoembryonic antigen in the patients with NSCLC were significantly higher (p < 0.05), while the expression level of high-density lipoprotein was lower (p < 0.05). The expression level of sLOX-1 in the serum of patients with healthy controls was positively correlated with low-density lipoprotein (r = 0.72, p < 0.05). The levels of sLOX-1 and low-density lipoprotein in the serum of patients with NSCLC were closely related to the lymph node metastasis, distant metastasis, and TNM stage (p < 0.05). Compared with a single index, when the sLOX-1 was combined with the CEA, its specificity increased significantly to 97.5% (AUC = 0.995, p < 0.01, 95% CI: 0.989-1.000). Conclusion: sLOX-1 and low-density lipoprotein were overexpressed in the serum of patients with NSCLC, positively correlated, and closely related to the TNM stage and metastasis. This result suggested that lipid metabolic disorders may promote the progression of NSCLC through sLOX-1, which could be a potential serological marker with diagnostic value for NSCLC.

GRK6 Depletion Induces HIF Activity in Lung Adenocarcinoma.

G protein-coupled receptor kinase 6 (GRK6) is expressed in various tissues and is involved in the development of several diseases including lung cancer. We previously reported that GRK6 is down-regulated in lung adenocarcinoma patients, which induces cell invasion and metastasis. However, further understanding of the role of GRK6 in lung adenocarcinoma is required. Here we explored the functional consequence of GRK6 inhibition in lung epithelial cells. Analysis of TCGA data was coupled with RNA sequencing (RNA-seq) in alveolar epithelial type II (ATII) cells following depletion of GRK6 with RNA interference (RNAi). Findings were validated in ATII cells followed by tissue microarray analysis. Pathway analysis suggested that one of the Hallmark pathways enriched upon GRK6 inhibition is 'Hallmark_Hypoxia' (FDR = 0.014). We demonstrated that GRK6 depletion induces HIF1α (hypoxia-inducible factor 1 alpha) levels and activity in ATII cells. The findings were further confirmed in lung adenocarcinoma samples, in which GRK6 expression levels negatively and positively correlate with HIF1α expression (P = 0.015) and VHL expression (P < 0.0001), respectively. Mechanistically, we showed the impact of GRK6 on HIF activity could be achieved via regulation of VHL levels. Taken together, targeting the HIF pathway may provide new strategies for therapy in GRK6-depleted lung adenocarcinoma patients.

Clinical value of serum and exhaled breath condensate inflammatory factor IL-11 levels in non-small cell lung cancer: Clinical value of IL-11 in non-small cell lung cancer.

OBJECTIVE: Our study aimed to observe and evaluate the clinical value of interleukin (IL)-11 in the serum and exhaled breath condensate of patients with non-small cell lung cancer (NSCLC). METHODS: A total of 91 patients with NSCLC and 72 healthy volunteers were included in this study. IL-11 concentration was determined by ELISA, and the relationship between IL-11 expression in serum and exhaled breath condensate specimens, and the clinicopathological characteristics of patients with NSCLC were analyzed. The relationship between serum IL-11 expression and traditional tumor markers and inflammation indicators of NSCLC was also analyzed. The correlation between serum IL-11 and exhaled breath condensate IL-11 level was determined. The receiver operating characteristic curve was used to evaluate the diagnostic value of IL-11 and carcinoembryonic antigen single and combined detection for NSCLC. The published data from online databases were used to analyze the relationship between the expression of IL-11 and the prognosis of NSCLC. RESULTS: IL-11 concentration in serum and exhaled breath condensate specimens of patients with NSCLC were significantly increased. IL-11 expression was positively correlated with lymph node metastasis, distant metastasis, tumor node metastasis stage, and tumor differentiation degree of NSCLC. The expression of IL-11 in serum was positively correlated with that in exhaled breath condensate specimens. IL-11 expression was closely related to that of neutrophil-to-lymphocyte ratio and carcinoembryonic antigen. The combination of serum IL-11 with exhaled breath condensate IL-11 and carcinoembryonic antigen showed significantly higher diagnostic value than any one marker alone. Besides, the high IL-11 expression was closely related to the poor prognosis of NSCLC. CONCLUSION: IL-11 can be used as a potential diagnostic and prognostic biomarker for NSCLC.

Advanced NSCLC Patients With EGFR T790M Harboring TP53 R273C or KRAS G12V Cannot Benefit From Osimertinib Based on a Clinical Multicentre Study by Tissue and Liquid Biopsy.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients treated with first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) almost always acquire resistance, and the development of novel techniques analyzing circulating tumor DNA (ctDNA) have made it possible for liquid biopsy to detect genetic alterations from limited amount of DNA with less invasiveness. While a large amount of patients with EGFR exon 21 p.Thr790 Met (T790M) benefited from osimertinib treatment, acquired resistance to osimertinb has subsequently become a growing challenge. METHODS: We performed tissue and liquid rebiopsy on 50 patients with EGFR-mutant NSCLC who acquired resistance to first-generation EGFR-TKIs. Plasma samples underwent droplet digital PCR (ddPCR) and next-generation sequencing (NGS) examinations. Corresponding tissue samples underwent NGS and Cobas® EGFR Mutation Test v2 (Cobas) examinations. RESULTS: Of the 50 patients evaluated, the mutation detection rates of liquid biopsy group and tissue biopsy group demonstrated no significant differences (41/48, 85.4% vs. 44/48, 91.7%; OR=0.53, 95% CI=0.15 to 1.95). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 78.3% (36/46, 95% CI=0.39 to 2.69). Moreover, our results showed that almost half of the patients (46%, 23/50) resistant to first-generation EGFR-TKI harbored p.Thr790 Met (T790M) mutation. 82.6% (19/23) of the T790M positive patients were analyzed by liquid biopsy and 60.9% (14/23) by tumor tissue sequencing. Meanwhile, a wide range of uncommon mutations was detected, and novel mechanisms of osimertinib resistance were discovered. In addition, 16.7% (2/12) of the T790M positive patients with either TP53 R237C or KRAS G12V failed to benefit from the subsequent osimertinib treatment. CONCLUSION: Our results emphasized that liquid biopsy is applicable to analyze the drug resistance mechanisms of NSCLC patients treated with EGFR-TKIs. Moreover, we discovered two uncommon mutations, TP53 R273C and KRAS G12V, which attenuates the effectiveness of osimertinib.

The value of red blood cell distribution width, neutrophil-to-lymphocyte ratio, and hemoglobin-to-red blood cell distribution width ratio in the progression of non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. Inflammation has been proven to be one of the characteristics of malignant tumors. Chronic inflammatory response mediated by cytokines in the tumor microenvironment is an important factor in tumorigenesis. The purpose of this study was to observe and evaluate the value of red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and hemoglobin-to-red blood cell distribution width ratio (HRR) in the progression of NSCLC. METHODS: A total of 245 patients with NSCLC, 97 patients with benign pulmonary nodules, and 94 healthy volunteers were included in this study. Factors, such as age, gender, smoking history, histological type, lymph node metastasis, distant metastasis, TNM stage, and differentiation degree were statistically analyzed. The correlation of RDW, NLR, and HRR of patients with NSCLC with other clinical experimental parameters were also analyzed. Then, the diagnostic value of RDW, NLR, and HRR in the progression of NSCLC was evaluated. RESULTS: RDW, NLR, and HRR could be used to distinguish patients with NSCLC from healthy controls (p < 0.05). In addition, only the RDW in the NSCLC group with III-IV stage was significantly different from that in the benign pulmonary nodules group (p = 0.033), while NLR and HRR could significantly distinguish patients with NSCLC and benign pulmonary nodules (p < 0.001). RDW and NLR were positively correlated with NSCLC stage, whereas HRR was negatively correlated with NSCLC stage. RDW, NLR, and HRR were also significantly associated with the differentiation degree of NSCLC (p < 0.05). The ROC curve analysis showed that the combination of RDW with NLR, HRR, and CEA could show significantly higher diagnostic value than any one marker alone (AUC = 0.925, 95% CI: 0.897-0.954, and sensitivity and specificity of 79.60% and 93.60%, respectively). CONCLUSION: RDW, NLR, and HRR can be utilized as simple and effective biomarkers for the diagnosis and evaluation of NSCLC progression.

Clinical Value of Serum and Exhaled Breath Condensate miR-186 and IL-1ß Levels in Non-Small Cell Lung Cancer.

OBJECTIVE: Our study aimed to investigate the expression level and clinical significance of serum and exhaled breath condensate miR-186 and IL-1ß in non-small cell lung cancer patients. METHODS: The serum and exhaled breath condensate specimens of 62 non-small cell lung cancer patients and 60 healthy controls were collected to detect miR-186 expression levels by real-time fluorescent quantitative PCR. Enzyme linked immunosorbent assay was applied to examine IL-1ß concentration. Statistical analyses were used to evaluate the correlation between miR-186 and IL-1ß in serum and clinicopathological features, traditional serum tumor markers, and inflammatory markers. The diagnostic efficacy of miR-186 and IL-1ß for non-small cell lung cancer was evaluated by receiver operating characteristic curve analysis. The correlation between miR-186 and IL-1ß was determined. RESULTS: ① The relative expression level of miR-186 was greatly reduced in the serum and EBC of patients with non-small cell lung cancer, and the miR-186 expression level was reduced in different TNM stages of non-small cell lung cancer, from the early to later stages. ② The IL-1ß concentration in serum and exhaled breath condensate of patients with non-small cell lung cancer was increased. ③ Serum miR-186 and IL-1ß levels were closely related to lymph node metastasis, and the low expression of serum miR-186 and the high concentration of IL-1ß were associated with higher serum carcinoembryonic antigen, C-reactive protein, and erythrocyte sedimentation rate levels. ④ ROC curve analysis showed that exhaled breath condensate miR-186 had higher area under the curve than serum miR-186, and the combined detection showed higher diagnostic efficacy than the separate detection. In addition, the combined detection of IL-1ß and miR-186 has a larger AUC than the separate detection of both. ⑤ The correlation between serum miR-186 and IL-1ß was negative. CONCLUSION: miR-186 and IL-1ß are expected to be potential diagnostic biomarkers for non-small cell lung cancer.

Significance of vascular endothelium growth factor testing in exhaled breath condensate of patients with acute respiratory distress syndrome.

OBJECTIVE: We aimed to observe and investigate the clinical significance of vascular endothelium growth factor (VEGF) levels in exhaled breath condensate (EBC) from patients with acute respiratory distress syndrome (ARDS). METHODS: An improved EcoScreen condenser was used to collect EBC from 31 ARDS patients on mechanical ventilation and from 22 healthy subjects. Serum and EBC VEGF levels were analyzed with ELISA. VEGF levels in the EBC of patients with different grades of lung injuries were analyzed. The correlation between VEGF levels and clinical indicators was analyzed. RESULTS: Serum and EBC VEGF levels were linearly and positively correlated with a correlation coefficient of 0.694 (P< 0.01). The VEGF level in the EBC of ARDS patients was significantly lower than that in the control group (P< 0.01). The VEGF level in the EBC of the mild ARDS group was higher than that in the moderate-severe ARDS group (P< 0.01). The VEGF level in the EBC of the survival group was higher than that in the mortality group. The VEGF level in the EBC of ARDS patients was positively correlated with PaO2/FiO2 and PaO2 and was negatively correlated with lung injury score (LIS) and A-aDO2/PaO2. CONCLUSION: The changes in VEGF levels in the EBC of ARDS patients can Respiratory Medicine, reflect the severity of lung injury. Therefore, VEGF level in EBC can be used as an auxiliary index for judging the severity and prognosis of ARDS patients.