Serum Of Lung Cancer Patients Research Articles

Dynamic mutation late acceptance hill climbing aided red fox optimization for metabolomic biomarkers selection from lung cancer patient sera

The accurate selection of serum metabolomic biomarkers for early lung cancer screening remains a significant challenge in the clinical context. Consequently, this study introduces the Red Fox Optimization (RFO) that integrates Dynamic Mutation Late Acceptance Hill Climbing (DM-LAHC), with the aim of selecting a panel of serum metabolomic biomarkers suitable for distinguishing between benign and malignant pulmonary nodules. The key innovation is the dynamic adjustment of the mutation probability in the Late Acceptance Hill Climbing algorithm, which greatly enhances the local search capabilities. And the RFO's reproduction mechanism has been improved through the utilization of a more efficient interpolation form. The biomarker selection model employs a multi-objective fitness function that takes into account both accuracy and quantity. After this, the optimal model yielded a biomarker panel, including Inosine, Hippuric acid, Alanine, and other metabolites. This model demonstrates outstanding performance on an independent test dataset, achieving a fitness value of 0.9136, an AUC (Area Under the Curve) of 0.9926, a sensitivity of 0.9643, and a specificity of 0.9412. Furthermore, the clinical net benefit is highlighted across various risk thresholds by decision curve analysis. These results underscore the significance of DM-LAHC aided RFO in the selection of serum metabolomic biomarkers for lung cancer. The supporting source codes of this work can be found at: https://github.com/zzl2022/DM-LAHC-aided-RFO.

The expression of miR-21, HSP90α and GASP-1 in serum of patients with lung cancer and their correlation with pathological subtypes

Background: To investigate the expression of miR-21, heat shock protein-90α (HSP90α) and G protein-coupled receptor-related sorting protein 1(GASP-1) in the serum of lung cancer patients and their correlation with pathological subtypes. 
 Methods: Eighty patients with lung cancer were included in the lung cancer group from May 2020 to May 2022, and 40 volunteers who underwent physical examination were randomly included in the control group according to the group ratio of 2:1. Serum miR-21, HSP90α and GASP-1 levels of patients in the two groups were detected. To explore the correlation between it and pathological subtypes, TNM stage and lymph node metastasis of lung cancer patients. 
 Results: The serum levels of miR-21, HSP90α and GASP-1 in lung cancer group were higher than those in control group (P < 0.05). ROC curve analysis showed that serum miR-21, HSP90α and GASP-1 levels had certain value in the diagnosis of lung cancer, and their AUC values were 0.901, 0.874 and 0.865, respectively (P < 0.05). There was no difference in the relative expression level of serum miR-21 between squamous cell carcinoma group and adenocarcinoma group (P>0.05), but the levels of HSP90α and GASP-1 in adenocarcinoma group were higher than those in squamous cell carcinoma group (P < 0.05). There was no difference in the levels of serum miR-21, HSP90α and GASP-1 between stage I and stage II groups (P>0.05). The levels of serum miR-21, HSP90α and GASP-1 in stage III and stage IV groups were higher than those in stage I and stage II groups, and those in stage IV were higher than those in stage III group (P < 0.05). The serum levels of miR-21, HSP90α and GASP-1 in patients with metastasis were higher than those in patients without metastasis (P < 0.05). 
 Conclusions: In patients with lung cancer, serum miR-21, HSP90α and GASP-1 levels were increased, which were associated with pathological subtypes, stage and lymph node metastasis, and had high diagnostic significance in the clinic.

LncRNA MIR31HG fosters stemness malignant features of non-small cell lung cancer via H3K4me1- and H3K27Ace-mediated GLI2 expression.

Non-coding RNAs are responsible for oncogenesis and the development of stemness features, including multidrug resistance and metastasis, in various cancers. Expression of lncRNA MIR31HG in lung cancer tissues and peripheral sera of lung cancer patients were remarkably higher than that of healthy individuals and indicated a poor prognosis. Functional analysis showed that MIR31HG fosters stemness-associated malignant features of non-small cell lung cancer cells. Further mechanistic investigation revealed that MIR31HG modulated GLI2 expression via WDR5/MLL3/P300 complex-mediated H3K4me and H3K27Ace modification. In vivo MIR31HG repression with an antisense oligonucleotide attenuated tumor growth and distal organ metastasis, whereas MIR31HG promotion remarkably encouraged cellular invasion in lung and liver tissues. Our data suggested that MIR31HG is a potential diagnostic indicator and druggable therapeutic target to facilitate multiple strategic treatments for lung cancer patients.

Combined SERS Microfluidic Chip with Gold Nanocone Array for Effective Early Lung Cancer Prognosis in Mice Model.

As the most common malignant tumor in the world, the prognosis of patients with advanced lung cancer remains poor even after treatment. There are many prognostic marker assays available, but there is still more room for the development of high-throughput and sensitive detection of circulating tumor DNA (ctDNA). Surface-enhanced Raman spectroscopy (SERS), a spectroscopic detection method that has received wide attention in recent years, can achieve exponential amplification of Raman signals by using different metallic nanomaterials. Integrating SERS with signal amplification strategy into the microfluidic chip and applying it to ctDNA detection is expected to be an effective tool for the prognosis of lung cancer treatment effect in the future. To construct a high-throughput SERS microfluidic chip integrated with enzyme-assisted signal amplification (EASA) and catalytic hairpin self-assembly (CHA) signal amplification strategies, using hpDNA-functionalized Au nanocone arrays (AuNCAs) as capture substrates and cisplatin-treated lung cancer mice to simulate the detection environment for sensitive detection of ctDNA in serum of lung cancer patients after treatment. The SERS microfluidic chip constructed by this scheme, with two reaction zones, can simultaneously and sensitively detect the concentrations of four prognostic ctDNAs in the serum of three lung cancer patients with a limit of detection (LOD) as low as the aM level. The results of the ELISA assay are consistent with this scheme, and its accuracy is guaranteed. This high-throughput SERS microfluidic chip has high sensitivity and specificity in the detection of ctDNA. This could be a potential tool for prognostic assessment of lung cancer treatment efficacy in future clinical applications.

Identification of hsa-miR-619-5p and hsa-miR-4454 in plasma-derived exosomes as a potential biomarker for lung adenocarcinoma.

Introduction: Lung cancer has long been at the forefront of all cancers in terms of incidence and mortality. Lung adenocarcinoma is the most common type of lung cancer, accounting for 40% of all lung cancer types. Exosomes can act as biomarkers of tumors and thus play an important role. Methods: In this article, high-throughput sequencing of miRNAs in plasma exosomes from lung adenocarcinoma patients and healthy individuals was performed to obtain 87 upregulated miRNAs, which were then combined with data from the GSE137140 database uploaded by others for screening. The database included 1566 preoperative lung cancer patients, 180 postoperative patients, and 1774 non-cancerous controls. We overlapped the miRNAs upregulated in the serum of lung cancer patients in the database relative to those of non-cancer controls and post-operative patients with the upregulated miRNAs obtained from our next-generation sequencing to obtain nine miRNAs. Two miRNAs that were not reported as tumor markers in lung cancer, hsa-miR-4454 and hsa-miR-619-5p, were selected from them and then validated by qRT-PCR, and further analysis of miRNAs was performed using bioinformatics. Results: Real-time quantitative PCR showed that the expression levels of hsa-miR-4454 and hsa-miR-619-5p in plasma exosomes of patients with lung adenocarcinoma were significantly up-regulated. The AUC values of hsa-miR-619-5p and hsa-miR-4454 were 0.906 and 0.975, respectively, both greater than 0.5, showing good performance. The target genes of miRNAs were screened by bioinformatics methods, and the regulatory network between miRNAs and lncRNAs and mRNAs was studied. Discussion: Our work demonstrated that hsa-miR-4454 and hsa-miR-619-5p have the potential to be used as biomarkers for the early diagnosis of lung adenocarcinoma.

Microporous PdCuB nanotag-based electrochemical aptasensor with Au@CuCl2 nanowires interface for ultrasensitive detection of PD-L1-positive exosomes in the serum of lung cancer patients

Programmed cell death ligand 1 protein-positive (PD-L1+) exosomes have been found to be a potential biomarker for the diagnosis of non-small cell lung cancer (NSCLC). However, the development of highly sensitive detection technique for PD-L1+ exosomes is still a challenge in clinical applications. Herein, a sandwich electrochemical aptasensor based on ternary metal-metalloid palladium-copper-boron alloy microporous nanospheres (PdCuB MNs) and Au@CuCl2 nanowires (NWs) was designed for the detection of PD-L1+ exosomes. The excellent peroxidase-like catalytic activity of PdCuB MNs and the high conductivity of Au@CuCl2 NWs endow the fabricated aptasensor with intense electrochemical signal, thus enabling the detection of low abundance exosomes. The analytical results revealed that the aptasensor maintained favorable linearity over a wide concentration range of 6 orders of magnitude and reached a low detection limit of 36 particles/mL. The aptasensor is successfully applied to the analysis of complex serum samples and achieves the accurate identification of clinical NSCLC patients. Overall, the developed electrochemical aptasensor provides a powerful tool for early diagnosis of NSCLC.

Extracellular vesicles derived from lung cancer cells promote the progression of lung cancer by delivering miR-151a-5p

Extracellular vesicles (EVs) participate in the occurrence and development of lung cancer. MiR-151a-5p has been reported to be highly expressed in the tumor tissues of lung cancer. The aim of this work was to investigate whether EVs can affect lung cancer progression by delivering miR-151a-5p. In this work, we found that miR-151a-5p was highly expressed in serum of lung cancer patients. Up-regulation of miR-151a-5p and down-regulation of Nedd4-binding partner-1 (N4BP1) were observed in lung cancer cell lines. The expression of miR-151a-5p was also increased in H520-derived EVs. H520-derived EVs promoted cell proliferation, inhibited apoptosis of H520 cells by delivering miR-151a-5p. EVs containing miR-151a-5p repressed E-cadherin expression and elevated N-cadherin and Vimentin expression to impede epithelial-mesenchymal transition (EMT) of H520 cells. Additionally, the interaction between miR-151a-5p and N4BP1 was verified by luciferase reporter assay, showing that miR-151a-5p interacted with N4BP1. MiR-151a-5p repressed N4BP1 expression by interacting with N4BP1. EVs containing miR-151a-5p promoted malignant phenotypes of H520 cells by targeting N4BP1. Finally, a tumor-bearing mouse model was constructed by inoculation of H520 cells with miR-151a-5p overexpression or knockdown. Overexpression of miR-151a-5p accelerated tumor growth of lung cancer in vivo, and repressed N4BP1 expression in the tumor tissues. Knockdown of miR-151a-5p caused opposite results. In conclusion, this work demonstrated that lung cancer cell-derived EVs secreted miR-151a-5p to promote cell proliferation, and inhibit apoptosis and EMT of lung cancer cells by targeting N4BP1, thereby accelerating lung cancer progression. Thus, this study suggests that EVs-derived miR-151a-5p may be a potential target for lung cancer treatment.

N-Glycan and Glycopeptide Serum Biomarkers in Philippine Lung Cancer Patients Identified Using Liquid Chromatography-Tandem Mass Spectrometry.

Aberrant glycosylation has been extensively reported in cancer, with fundamental changes in the glycosylation patterns of cell-surface and secreted proteins largely occurring during cancer progression. As such, serum glycan and glycopeptide biomarkers have been discovered using mass spectrometry and proposed for cancer detection. Here, we report for the first time potential serum N-glycan and glycopeptide biomarkers for Philippine lung cancer patients. The N-glycan and glycoprotein profiles of a cohort (n = 26 patients, n = 22 age- and gender-matched) of lung cancer patients were analyzed and compared to identify potential N-glycan and glycopeptide serum biomarkers using nano-QToF-MS/MS and ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry dynamic multiple monitoring methods, respectively. Statistical analyses identified differential N-glycan and glycopeptide abundances. The N-glycans were mostly sialylated and sialofucosylated branched structures. The glycopeptides involved proteins in complement and coagulation cascades (p adj = 6.418 × 10-4), innate immunity (p adj = 6.094 × 10-3), acute inflammatory response (p adj = 6.404 × 10-5), defense response (p adj = 2.082 × 10-4), complement activation pathways (p adj = 1.895 × 10-2), and immunoglobulin-mediated immune response pathways (p adj = 4.818 × 10-2). Biomarker models were constructed using serum N-glycans [area under the curve (AUC) = 0.775; 95% CI: 0.617-0.931] and glycopeptides (AUC = 0.959; 95% CI: 0.85-1.0), with glycopeptides having higher accuracies than N-glycans. The results suggest that in the Philippine lung cancer patient sera, specific N-glycans and site-specific glycans are differentially expressed between cases and controls. This report represents the first serum glycan and glycopeptide biomarkers of Philippine lung cancer patients, further demonstrating the utility of mass spectrometry-based glycomic and glycoproteomic methods.

Relationship between Trace Elements Levels and Lung Cancer Patients in Southern Iraq

Background: Our life relies on our ability to use all sorts of materials, like trace elements, in the world for our needs. The using of heavy metals has greatly contributed to the comfort of our everyday lives. Blood is directly affected by poisoning when such metals are inhaled from environments where heavy metals occur in high levels. Research is constantly advancing our knowledge of the connection between various trace elements and disease, particularly cancer, since the effects of heavy metals on human health remain a serious health concern.
 Objective: The objective of this work is to establish levels of a range of elements in human blood, serum and hair samples of patient undergo lung cancer comparing with control (healthy persons) so that potential exposures can be better identified in future cases.
 Methods: Elements concentrations including As(arsenic), Ba(barium), Co(cobalt), Li(lithium), Mg(magnesium), Mn(manganese), Mo(molybdenum), Rb(rubidium), Sr(strontium) and Ti(titanium) was analysis used MS ICP (an inductively coupled plasma atomic absorption spectrophotometer).
 Results: Test found that Mn has substantially (p<0.05) high concentration in three tissues including whole blood, serum, and hair of patients with lung cancer (291,487.2,68.03) ug / l respectively. In comparison as occurs in the lowest concentration. Sr was 77.5ug / l, Rb 41.6ug / l, and Ba 35.2ug / g. On other hand, Co, Li, Mg, Mo and Ti were found in low levels ranged 1.7-5.5 ug/l, in whole blood of patients. Hair samples accumulated the lowest concentration of As, Ba, Co, Mg, Mn and Rb. When we compare the concentration of trace elements between lung patients and control samples, that clear most of the elements accumulate at high levels in lung cancer patients. Result found significantly high As, Ba, Co, Mg, Mo concentration in whole blood and serum of lung cancer patients, in contract, Li, Mn and Rb occur in high levels in whole blood of control sample. Even as hair of control samples have elevated levels of As, Sr and Ti. However, concentrations of trace elements in the whole blood of smokers and non-smokers showed that all ten elements accumulated at elevated levels in the blood of smokers relative to non-smokers. Spearman correlation found significantly positive correlation among trace elements in the blood of patients with smoker lung cancer and non-smokers.
 Conclusion: The study conclude that trace metals level in smokers persons are elevated than non-smokers. The findings of this study lend some support to the link between heavy metals pollution and lung cancer cases.

Expression of SARS-CoV-2-Related Surface Proteins in Non-Small-Cell Lung Cancer Patients and the Influence of Standard of Care Therapy.

Simple SummarySARS-CoV-2 is a respiratory virus that uses ACE2 for host cell entry and the spike protein is primed by, among others, TMPRSS2 and FURIN. The goal of this study was to determine in which non-small-cell lung cancer (NSCLC) patients these proteins are expressed on the membrane of the lung cancer cells and in which patients this increased ACE2 expression results in higher levels of soluble (s)ACE2 in their serum. In addition, we studied the influence of standard of care (SOC) therapies on sACE2 levels. Membranous (m)ACE2 was co-expressed with mFURIN and/or mTMPRSS2 in 16% of the NSCLC patients, and mACE2 and sACE2 were more frequently expressed in mutant EGFR patients but not mutant-KRAS patients. Importantly, systemic SOC therapies did not result in increased sACE2 levels. This indicates that cancer cells can be infected by SARS-CoV-2 in these patients, as well as that soluble ACE2 could impact the course of COVID-19.In this study, we aimed to study the expression of SARS-CoV-2-related surface proteins in non-small-cell lung cancer (NSCLC) cells and identify clinicopathological characteristics that are related to increased membranous (m)ACE2 protein expression and soluble (s)ACE2 levels, with a particular focus on standard of care (SOC) therapies. ACE2 (n = 107), TMPRSS2, and FURIN (n = 38) protein expression was determined by immunohistochemical (IHC) analysis in NSCLC patients. sACE2 levels (n = 64) were determined in the serum of lung cancer patients collected before, during, or after treatment with SOC therapies. Finally, the TCGA lung adenocarcinoma (LUAD) database was consulted to study the expression of ACE2 in EGFR- and KRAS-mutant samples and ACE2 expression was correlated with EGFR/HER, RAS, BRAF, ROS1, ALK, and MET mRNA expression. Membranous (m)ACE2 was found to be co-expressed with mFURIN and/or mTMPRSS2 in 16% of the NSCLC samples and limited to the adenocarcinoma subtype. TMPRSS2 showed predominantly atypical cytoplasmic expression. mACE2 and sACE2 were more frequently expressed in mutant EGFR patients, but not mutant-KRAS patients. A significant difference was observed in sACE2 for patients treated with targeted therapies, but not for chemo- and immunotherapy. In the TCGA LUAD cohort, ACE2 expression was significantly higher in EGFR-mutant patients and significantly lower in KRAS-mutant patients. Finally, ACE2 expression was positively correlated with ERBB2-4 and ROS1 expression and inversely correlated with KRAS, NRAS, HRAS, and MET mRNA expression. We identified a role for EGFR pathway activation in the expression of mACE2 in NSCLC cells, associated with increased sACE2 levels in patients. Therefore, it is of great interest to study SARS-CoV-2-infected EGFR-mutated NSCLC patients in greater depth in order to obtain a better understanding of how mACE2, sACE2, and SOC TKIs can affect the course of COVID-19.

Assessment of iron status markers in patients with lung cancer

Lung cancer is one of the most diagnosed diseases in men and women and is the leading cause of cancer-related mortality worldwide. The purpose of this study is to examine the impact of lung cancer on the role of iron status markers in patient serum. The present study included fifty (50) lung cancer patients (males and females) and forty (40) healthy subjects. The levels of iron status markers that include iron, ferritin, transferrin, transferrin saturation (TS%), total iron binding capacity (TIBC), and unsaturated iron binding capacity (UIBC) were estimated in the serum of lung cancer patients, as well as the value of interleukin 6 (IL-6) were recorded. Generally, the results of the present study revealed significant differences (p<0.05) in the levels of iron status markers and IL-6 in the serum of lung cancer patients in comparison with the control groups. The findings of this study suggest that these indicators play an important role in lung cancer at multiple levels and that the specific activity of these biomarkers may be relevant as an independent predictor of lung cancer disease progression.

Evaluation of some hematological criteria in lung cancer patients

Lung cancer is one of the most commonly diagnosed diseases in both men and women and the leading cause of cancer-related death worldwide. This study aims to investigate the effect of lung cancer on the role of some hematological criteria in patient serum. There were fifty (50) lung cancer patients (males and females) and forty (40) healthy subjects in the present study. The levels of some hematological parameters that include erythrocyte indices [red blood cell (RBCs) count, hemoglobin (Hb), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), and red cell distribution width (RDW)], leukocyte indices [total white blood cell (WBCs) count, neutrophil percentage (%), lymphocyte percentage (%)], and thrombocyte indices [platelet count and mean platelet volume (MPV)] was recorded. In general, the levels of all hematological criteria in the serum of lung cancer patients were significantly different (p<0.05) from those of the control groups. In conclusion, hematological measurements can provide important prognostic information for patients with lung cancer, and they are simple and readily available at medical centers.

Assessment of iron status markers in patients with lung cancer

Lung cancer is one of the most diagnosed diseases in men and women and is the leading cause of cancer-related mortality worldwide. The purpose of this study is to examine the impact of lung cancer on the role of iron status markers in patient serum. The present study included fifty (50) lung cancer patients (males and females) and forty (40) healthy subjects. The levels of iron status markers that include iron, ferritin, transferrin, transferrin saturation (TS%), total iron binding capacity (TIBC), and unsaturated iron binding capacity (UIBC) were estimated in the serum of lung cancer patients, as well as the value of interleukin 6 (IL-6) were recorded. Generally, the results of the present study revealed significant differences (p<0.05) in the levels of iron status markers and IL-6 in the serum of lung cancer patients in comparison with the control groups. The findings of this study suggest that these indicators play an important role in lung cancer at multiple levels and that the specific activity of these biomarkers may be relevant as an independent predictor of lung cancer disease progression.

Evaluation of some hematological criteria in lung cancer patients

 
 Lung cancer is one of the most commonly diagnosed diseases in both men and women and the leading cause of cancer-related death worldwide. This study aims to investigate the effect of lung cancer on the role of some hematological criteria in patient serum. There were fifty (50) lung cancer patients (males and females) and forty (40) healthy subjects in the present study. The levels of some hematological parameters that include erythrocyte indices [red blood cell (RBCs) count, hemoglobin (Hb), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), and red cell distribution width (RDW)], leukocyte indices [total white blood cell (WBCs) count, neutrophil percentage (%), lymphocyte percentage (%)], and thrombocyte indices [platelet count and mean platelet volume (MPV)] was recorded. In general, the levels of all hematological criteria in the serum of lung cancer patients were significantly different (p<0.05) from those of the control groups. In conclusion, hematological measurements can provide important prognostic information for patients with lung cancer, and they are simple and readily available at medical centers.

Differentiation of Sialyl Linkages Using a Combination of Alkyl Esterification and Phenylhydrazine Derivatization: Application for N-Glycan Profiling in the Sera of Patients with Lung Cancer.

Alterations in oligosaccharides and types of sialic acid (SA) attachments have been associated with different pathological states. Matrix-assisted laser desorption mass spectrometry (MS) is commonly used for glycosylation studies. However, native sialylated glycans are suppressed or not detected during MS experiments. Consequently, different approaches have been employed to neutralize the negative charge of the carboxyl group. In this study, we present the advantage of phenylhydrazine (PHN) labeling for the detection and efficient discrimination of SA linkages when this derivatization follows alkyl esterification. As expected, PHN-labeled sialylated oligosaccharides with the 2,6-linkage type can be easily recognized according to the additional shift in mass corresponding to the presence of a methyl or ethyl group. Surprisingly, oligosaccharides with the 2,3-linked SA residue instead of a lactone were detected carrying the second PHN unit. This was beneficial as no further processing after esterification was needed to stabilize the lactone form. Moreover, during tandem mass experiments, all modified glycans produced favorable fragmentation patterns with a coherent recognition of SA linkages. Although both types of esterification, herein called the EST-PHN approach, provided comparable results, methylation exhibited marginally higher linkage specificity than ethyl esterification. The simplicity and effectiveness of the methodology are demonstrated on the model compound, sialyllactose, and its applicability for biological studies is presented on N-glycan profiling in the sera of lung cancer patients.

Detection of leucine-rich alpha-2-glycoprotein 1 containing immunocomplexes in the plasma of lung cancer patients with epitope-specific mAbs.

Lung cancer is the leading cause of cancer-related deaths worldwide. With the expectation of improved survival, tremendous efforts and resources have been invested in the discovery of specific biomarkers for early detection of the disease. Several investigators have reported the presence of cancer-associated autoantibodies in the plasma or serum of lung cancer patients. Previously, we used a monoclonal antibody (mAb) proteomics technology platform for the discovery of novel lung cancer-associated proteins. The identification of specific protein epitopes associated with various cancers is a promising method in biomarker discovery. Here, in a preliminary study, we aimed to detect autoantibody-leucine-rich alpha-2-glycoprotein 1 (LRG1) immunocomplexes using epitope-specific monoclonal antibodies (mAbs). We performed sandwich ELISA assays using the LRG1 epitope-specific capture mAbs, Bsi0352 and Bsi0392, and an IgG-specific polyclonal antibody coupled to a reporter system as the detection reagent. We tested the plasma of lung cancer patients and apparently healthy controls. Depending on the epitope specificity of the capture mAb, we were either unable to distinguish the control from LC-groups or showed a higher level of LRG1 and IgG autoantibody containing immunocomplexes in the plasma of non-small cell lung cancer and small cell lung cancer subgroups of lung cancer patients than in the plasma of control subjects. Our findings underline the importance of protein epitope-specific antibody targeted approaches in biomarker research, as this may increase the accuracy of previously described tests, which will need further validation in large clinical cohorts.

Exosomal microRNAs array sensor with a bioconjugate composed of p53 protein and hydrazine for the specific lung cancer detection

For the early diagnosis of lung cancer, a novel strategy to detect microRNAs encapsulated in exosomes with immunomagnetic isolation was demonstrated for the selective extraction of exo-miRNAs from patient serum. Here, miRNA was captured from lysed exosomes in specially designed capture probe modified magnetic beads, followed by T4 DNA polymerase-mediated in situ formation of chimeric 5′-miRNA-DNA-3′ (Target). The poly-(2,2′:5′,2′′-terthiophene-3′-(p-benzoic acid)) (pTBA)-modified electrode harbors Probe-1 DNA that hybridizes to the 5′ end of the chimera, followed by hybridization of Probe-2 DNA to the 3′ end of the chimera, resulting in the formation of a 20-nucleotide-long dsDNA consensus sequence for p53 protein binding. A bioconjugate composed of p53 and hydrazine assembled on AuNPs (p53-AuNPs-Hyd) recruits the p53 protein to recognize a specific sequence, forming the final sensor probe (pTBA-Probe-1:Target/Probe-2:bioconjugate), where hydrazine functions as an electrocatalyst to generate amperometric signal from the reduction of H2O2. This sensor has double specificity via selective capture of the target in Probe-1 and p53 recognition, which shows excellent analytical performance, revealing a dynamic range between 100 aM and 10 pM with a detection limit of 92 (±0.1) aM. For practical applications, we prepared a multiplexed array sensor to simultaneously detect four exo-miRNAs (miRNA-21, miRNA-155, miRNA-205, and miRNA-let-7b) up to femtomolar levels from 1.0 mL to 125 μL of cell culture (A549, MCF-7 and BEAS-2B) media and lung cancer patient serum samples, respectively.

Participation of Increased Circulating MAIT Cells in Lung Cancer: a Pilot Study

Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that regulate the immune response via rapidly releasing inflammatory factors, including during progression of some tumors. However, the immunological role of MAIT cells is still unclear in lung cancer. We measured percentage, partial function, and clinical correlation of circulating MAIT cells from lung cancer patients through flow cytometry. Lung cancer patients displayed a high concentration of CD4+, CD8+, and activated CD38+CD8+MAIT cells, and a decrease of PD1+ double negative (DN) MAIT cells in peripheral blood. Meanwhile, increased levels of interferon-γ, interleukin (IL)-6, and 8 were examined in the serum of lung cancer patients. Importantly, we discovered a statistically positive association between accumulation of CD38+CD8+MAIT cells and reduced progression-free survival of lung cancer patients. While preliminary, the altering frequency of MAIT cells might be involved in dysfunctional immune response in lung cancer.

Combining MALDI-MS with machine learning for metabolomic characterization of lung cancer patient sera.

An increasing amount of evidence has proven that serum metabolites can instantly reflect disease states. Therefore, sensitive and reproducible detection of serum metabolites in a high-throughput manner is urgently needed for clinical diagnosis. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a high-throughput platform for metabolite detection, but it is hindered by significant signal fluctuations because of the "sweet spot" effect of organic matrices. Here, by screening two transformation methods and four normalization techniques to reduce the significant signal fluctuations of the DHB matrix, an integrated MALDI-MS data processing approach combined with machine learning methods was established to reveal metabolic biomarkers of lung cancer. In our study, 13 distinctive features with statistically significant differences (p < 0.001) between 34 lung cancer patients and 26 healthy controls were selected as significant potential biomarkers of lung cancer. 6 out of the 13 distinctive features were identified as intact metabolites. Our results demonstrate the potential for clinical application of MALDI-MS in serum metabolomics for biomarker screening in lung cancer.

Detection of antibodies against benzo[a]pyrene in blood sera of lung cancer patients by ELISA using human recombinant idiotypic and anti-idiotypic antibodies.

ELISA was developed and applied for the detection of endogenous idiotypic and anti-idiotypic antibodies against Bp in human blood sera using recombinant human idiotypic and anti-idiotypic antibodies against Bp. Serum samples of LC patients (n = 22) and healthy donors (n = 24) were analyzed by the new method. Statistical analysis showed that in sera of LC patients the levels of endogenous idiotypic and anti-idiotypic antibodies against Bp were significantly higher than in healthy donors. A logistic regression model for the LC detection utilizing such predictors as the serum levels of idiotypic and anti-idiotypic antibodies against Bp, smoking status, and age, identified LC patients with 83% specificity and 82% sensitivity. The proposed method could be further developed as additional lung cancer screening tool.