Exploring the Prognostic Value and Immune Infiltration Patterns of GPRC5A Across Multiple Cancer Types.

Objective: This study aimed to investigate the expression of GPRC5A in pan-cancer and its correlation with clinical outcomes, tumor immune microenvironment, and biological functions. Methods: The expression of GPRC5A was analyzed using 33 tumor datasets from the TCGA, GTEx and TCGA databases. Immunohistochemical images from the HPA database were also examined. Kaplan-Meier survival analysis was conducted to assess the prognostic value of GPRC5A. Correlations between GPRC5A expression and clinical parameters were investigated. Nomogram models were developed to predict survival probabilities. The correlation between GPRC5A expression and tumor immune microenvironment was analyzed using the GEPIA2 database. Functional enrichment analysis and Gene Set Enrichment Analysis were performed to explore the biological functions associated with GPRC5A. Results: GPRC5A exhibited varying expression levels across different types of tumors, with high expression observed in 11 types of cancer tissues. Aberrant GPRC5A expression was correlated with overall survival, disease-specific survival, and progression-free interval in specific cancers. Specific clinicopathological features were found to be associated with GPRC5A expression in six tumors. Nomogram models incorporating GPRC5A expression demonstrated significant clinical utility in predicting survival probabilities for patients with ACC, KIRC, LGG, and PAAD. GPRC5A was also found to be associated with the tumor immune microenvironment. Functional enrichment analysis revealed the involvement of GPRC5A-related genes in various biological processes and functions. Conclusion: This study highlights the differential expression of GPRC5A in pan-cancer and its correlation with clinical outcomes. GPRC5A shows potential as a prognostic biomarker and therapeutic target in specific cancers. Moreover, its association with the tumor immune microenvironment suggests its involvement in the tumor immune response. The findings provide valuable insights into the biological roles of GPRC5A in tumors and contribute to our understanding of its clinical implications.

Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.

Recent progress in aqueous aluminum-ion batteries.

Aqueous aluminum-ion batteries have many advantages such as their safety, environmental friendliness, low cost, high reserves and the high theoretical specific capacity of aluminum. So aqueous aluminum-ion batteries are potential substitute for lithium-ion batteries. In this paper, the current research status and development trends of cathode and anode materials and electrolytes for aqueous aluminum-ion batteries are described. Aiming at the problem of passivation, corrosion and hydrogen evolution reaction of aluminum anode and dissolution and irreversible change of cathode after cycling in aqueous aluminum-ion batteries. Solutions of different research routes such as ASEI (artificial solid electrolyte interphase), alloying, amorphization, elemental doping, electrolyte regulation, etc and different transformation mechanisms of anode and cathode materials during cycling have been summarized. Moreover, it looks forward to the possible research directions of aqueous aluminum-ion batteries in the future. We hope that this review can provide some insights and support for the design of more suitable electrode materials and electrolytes for aqueous aluminum-ion batteries.

Synergistic effect of modified anhydrous magnesium carbonate and hexaphenoxycyclotriphosphazene on flame retardancy of ethylene-vinyl acetate copolymer.

Ethylene-vinyl acetate copolymer (EVA) is widely used in various applications; however, its flammability limits its application in wire and cable industries. In this study, 3-methacryloxypropyltrimethoxysilane (KH570) was successfully grafted onto the surface of anhydrous magnesium carbonate (AMC) by alkali activation treatment. The KH570 modified AMC (AMC@KH570) was then introduced into the EVA matrix along with hexaphenoxycyclotriphosphazene (HPCTP) to assess their effects on the flame retardancy and mechanical properties of EVA composites. The results illustrate a significant synergistic effect in enhancing the flame retardancy of EVA composites by using AMC@KH570 and HPCTP, and the limiting oxygen index (LOI) and vertical burning test (UL-94) of EVA filled with 5 wt% HPCTP and 45 wt% AMC@KH570 (mAMC/H-45-5) reached 27.6% and V-0, respectively. The flame retardant mechanism was investigated by thermogravimetric/infrared (TG-IR) spectroscopy and residual carbon composition analysis. The results show that the thermal decomposition of AMC@KH570 and HPCTP consists of gas dilution, free radical quenching, and catalytic carbonization. Furthermore, KH570 works as a bridge to improve the compatibility of AMC and EVA matrix, which offsets the mechanical loss of EVA to some extent. The present research provides a new path to modify AMC and fabricate EVA composites with excellent flame retardant properties.

Oncogenic functions and therapeutic potentials of targeted inhibition of SMARCAL1 in small cell lung cancer.

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.

Norcantharidin inhibits the malignant progression of cervical cancer by inducing endoplasmic reticulum stress.

The antitumor effect of norcantharidin (NCTD) has been widely reported. However, whether NCTD can inhibit cervical cancer remains unknown. In the present study, it was shown that NCTD inhibited the viability of cervical cancer cells and caused cell cycle arrest in a concentration­dependent manner. Further analysis revealed that the NCTD­induced reduction in cell viability could be reversed by the inhibitor of apoptosis z­VAD­FMK and by the inhibitor of endoplasmic reticulum (ER) stress, 4­phenylbutyric acid (4­PBA). Additionally, NCTD led to the accumulation of reactive oxygen species as well as a decrease in the mitochondrial membrane potential in cervical cancer cells, whereas 4­PBA pre­treatment attenuated these alterations. In addition, NCTD increased the expression of the apoptosis­related proteins Bip, activating transcription factor (ATF) 4 and C/EBP homologous protein in a concentration­dependent manner. Moreover, NCTD significantly increased the expression of the ER stress­related signaling molecules protein kinase R­like ER kinase, inositol­requiring enzyme 1 and ATF6, but 4­PBA abolished these effects. In vivo experiments showed that NCTD significantly inhibited the growth of subcutaneous tumors in mice. Additionally, the expression of ER stress­related molecules and apoptosis­related proteins increased significantly after NCTD treatment. In conclusion, NCTD induces apoptosis by activating ER stress and ultimately curtails the progression of cervical cancer.

CIP2A induces PKM2 tetramer formation and oxidative phosphorylation in non-small cell lung cancer.

Tumor cells are usually considered defective in mitochondrial respiration, but human non-small cell lung cancer (NSCLC) tumor tissues are shown to have enhanced glucose oxidation relative to adjacent benign lung. Here, we reported that oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibited glycolysis and promoted oxidative metabolism in NSCLC cells. CIP2A bound to pyruvate kinase M2 (PKM2) and induced the formation of PKM2 tetramer, with serine 287 as a novel phosphorylation site essential for PKM2 dimer-tetramer switching. CIP2A redirected PKM2 to mitochondrion, leading to upregulation of Bcl2 via phosphorylating Bcl2 at threonine 69. Clinically, CIP2A level in tumor tissues was positively correlated with the level of phosphorylated PKM2 S287. CIP2A-targeting compounds synergized with glycolysis inhibitor in suppressing cell proliferation in vitro and in vivo. These results indicated that CIP2A facilitates oxidative phosphorylation by promoting tetrameric PKM2 formation, and targeting CIP2A and glycolysis exhibits therapeutic potentials in NSCLC.

Multimodal fusion of liquid biopsy and CT enhances differential diagnosis of early-stage lung adenocarcinoma.

This research explores the potential of multimodal fusion for the differential diagnosis of early-stage lung adenocarcinoma (LUAD) (tumor sizes < 2 cm). It combines liquid biopsy biomarkers, specifically extracellular vesicle long RNA (evlRNA) and the computed tomography (CT) attributes. The fusion model achieves an impressive area under receiver operating characteristic curve (AUC) of 91.9% for the four-classification of adenocarcinoma, along with a benign-malignant AUC of 94.8% (sensitivity: 89.1%, specificity: 94.3%). These outcomes outperform the diagnostic capabilities of the single-modal models and human experts. A comprehensive SHapley Additive exPlanations (SHAP) is provided to offer deep insights into model predictions. Our findings reveal the complementary interplay between evlRNA and image-based characteristics, underscoring the significance of integrating diverse modalities in diagnosing early-stage LUAD.

Acetylshikonin induces apoptosis through the endoplasmic reticulum stress-activated PERK/eIF2α /CHOP axis in oesophageal squamous cell carcinoma.

Acetylshikonin (AS) is an active component of Lithospermum erythrorhizon Sieb. et Zucc that exhibits activity against various cancers; however, the underlying mechanisms of AS against oesophageal squamous carcinoma (ESCC) need to be elusive. The research explores the anti-cancer role and potential mechanism of AS on ESCC in vitro and in vivo, providing evidences for AS treatment against ESCC. In this study, we firstly demonstrated that AS treatment effectively inhibits cell viability and proliferation of ESCC cells. In addition, AS significantly induces G1/S phage arrest and promotes apoptosis in ESCC cell lines. Further studies reveal that AS induces ER stress, as observed by dose- and time-dependently increased expression of BIP, PDI, PERK, phosphorylation of eIF2α , CHOP and splicing of XBP1. CHOP knockdown or PERK inhibition markedly rescue cell apoptosis induced by AS. Moreover, AS treatment significantly inhibits ESCC xenograft growth in nude mice. Elevated expression of BIP and CHOP is also observed in xenograft tumours. Taken together, AS inhibits proliferation and induces apoptosis through ER stress-activated PERK/eIF2α /CHOP pathway in ESCC, which indicates AS represents a promising candidate for ESCC treatment.

Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated by Clonorchis sinensis infection.

Background: Clonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection. Methods: A total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis. Result: A total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI- modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in "Glutathione metabolism", "Caffeine metabolism", "Alanine, aspartate and glutamate metabolism", "Arginine and proline metabolism", "Purine metabolism", "Beta-Alanine metabolism", and "D-glutamine and D-glutamate metabolism". Conclusion: These results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.

Effect of Different Compatibilizers on the Mechanical, Flame Retardant, and Rheological Properties of Highly Filled Linear Low-Density Polyethylene/Magnesium Hydroxide Composites.

Maleic anhydride-modified homopolymerized polypropylene (PP-g-MAH) and maleic anhydride-modified polyolefin elastomer (POE-g-MAH) were used as bulking agents to improve the poor processing and mechanical properties of highly filled composites due to high filler content. In this study, a series of linear low-density polyethylene (LLDPE)/magnesium hydroxide (MH) composites were prepared by the melt blending method, and the effects of the compatibilizer on the mechanical properties, flame retardancy, and rheological behavior of the composites were investigated. The addition of the compatibilizer decreased the limiting oxygen index (LOI) values of the composites, but they were all greater than 30.00%, which belonged to the flame retardant grade. Mechanical property tests showed that the addition of the compatibilizer significantly increased the tensile and impact strengths of the LLDPE/60MH (MH addition of 60 wt%) composites. Specifically, the addition of 5 wt% POE-g-MAH increased 154.07% and 415.47% compared to the LLDPE/60MH composites, respectively. The rotational rheology test showed that the addition of the compatibilizer could effectively improve the processing flow properties of the composites. However, due to the hydrocarbon structure of the compatibilizer, its flame retardant properties were adversely affected. This study provides a strategy that can improve the processing and mechanical properties of highly filled composites.

High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

Association between short-term exposure to PM2.5 and nasal microbiota dysbiosis, inflammation and oxidative stress: A panel study of healthy young adults.

Fine particulate matter (PM2.5) is the primary environmental stressor and a significant threat to public health. However, the effect of PM2.5 exposure on human nasal microbiota and its pathophysiological implication remain less understood. This study aimed to explore the associations of PM2.5 exposure with indices of nasal microbiota and biomarkers of nasal inflammation and oxidative stress. We conducted a panel study with 75 students in Xinxiang, Henan Province, China, from September to December 2017. Biomarkers of nasal inflammation and oxidative stress including interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), 8-epi-prostaglandin F2 alpha (8-epi-PGF2α) and indices of nasal microbiota diversity and phenotypes were measured. Linear mixed-effect models and bioinformatic analyses were performed to assess the association of PM2.5 concentrations with the abovementioned biomarkers and indices. It was found that per 1 µg/m3 increase in PM2.5 was associated with increments of 13.15% (95 % CI: 5.53-20.76 %) and 78.98 % (95 % CI: 21.61-136.36 %) in TNF-α on lag2 and lag02. Indices of microbial diversity and phenotypes including equitability, Shannon index, biofilm forming, and oxidative stress tolerant decreased to different extent with the increment in PM2.5. Notably, thirteen differential microbes in Clostridia, Bacilli, and Gammaproteobacteria classes were recognized as keystone taxa and eight of them were associated with TNF-α, IL-6, or 8-epi-PGF2α. Moreover, environmental adaptation was the most critical functional pathway of nasal microbiota associated with PM2.5 exposure. In summary, short-term exposure to PM2.5 is associated with nasal inflammation, microbiota diversity reduction, and the microbiota phenotype alterations.

Serum Alpha-Fetoprotein as a Predictor of Liver Fibrosis in HBeAg-Positive Chronic Hepatitis B Patients.

Background and Objectives: Non-invasive methods for evaluating liver fibrosis have been a crucial focus of clinical research. The aim of the current study is to assess the accuracy of serum alpha-fetoprotein (AFP) in determining the stage of liver fibrosis in patients with chronic hepatitis B (CHB) who are positive for HBeAg. Materials and Methods: The current study included a total of 276 HBeAg-positive CHB patients who underwent liver biopsy. The levels of serum AFP were measured in these patients using electrochemiluminescence immunoassays. The correlations between serum AFP levels and other laboratory parameters were analyzed using Spearman's correlation analysis. Binary logistic regression analysis was performed to determine the independent associations between serum AFP levels and liver fibrosis. The diagnostic performance of serum AFP and other non-invasive markers was evaluated using receiver operating characteristic (ROC) curves. Results: A total of 59 (21.4%) patients were found to have elevated levels of serum AFP (>7 ng/mL). These patients displayed a significantly higher proportion of both advanced fibrosis and cirrhosis compared to those with normal serum AFP levels (0-7 ng/mL). The level of serum AFP was positively associated with levels of serum globulin (GLB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL), as well as the AST-to-platelet ratio (APRI), fibrosis-4 (FIB-4), and Scheuer's classification, and negatively correlated with platelet (PLT) counts. Furthermore, serum AFP was found to be independently associated with significant fibrosis, advanced fibrosis, and cirrhosis. The results of the ROC analysis showed that serum AFP was an effective predictor of significant fibrosis, advanced fibrosis, and cirrhosis, with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95% CI: 0.721-0.821), 0.889 (95% CI: 0.847-0.923), and 0.925 (95% CI: 0.887-0.953), respectively. These values are higher than those of the APRI and FIB-4. Conclusions: Serum AFP could serve as a valuable supplemental biomarker for determining the severity of liver fibrosis in HBeAg-positive patients with chronic hepatitis B.

MTSS1 curtails lung adenocarcinoma immune evasion by promoting AIP4-mediated PD-L1 monoubiquitination and lysosomal degradation.

Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has shown durable clinical benefits in lung cancer. However, many patients respond poorly to ICB treatment, underscoring an incomplete understanding of PD-L1 regulation and therapy resistance. Here, we find that MTSS1 is downregulated in lung adenocarcinoma, leading to PD-L1 upregulation, impairment of CD8+ lymphocyte function, and enhanced tumor progression. MTSS1 downregulation correlates with improved ICB efficacy in patients. Mechanistically, MTSS1 interacts with the E3 ligase AIP4 for PD-L1 monoubiquitination at Lysine 263, leading to PD-L1 endocytic sorting and lysosomal degradation. In addition, EGFR-KRAS signaling in lung adenocarcinoma suppresses MTSS1 and upregulates PD-L1. More importantly, combining AIP4-targeting via the clinical antidepressant drug clomipramine and ICB treatment improves therapy response and effectively suppresses the growth of ICB-resistant tumors in immunocompetent mice and humanized mice. Overall, our study discovers an MTSS1-AIP4 axis for PD-L1 monoubiquitination and reveals a potential combinatory therapy with antidepressants and ICB.

Morphological and Compositional Features of Chronic Internal Carotid Artery Occlusion in MR Vessel Wall Imaging Predict Successful Endovascular Recanalization.

Background: We sought to determine if the morphological and compositional features of chronic internal carotid artery occlusion (CICAO), as assessed by MR vessel wall imaging (MR-VWI), initially predict successful endovascular recanalization. Methods: Consecutive patients with CICAO scheduled for endovascular recanalization were recruited. MR-VWI was performed within 1 week prior to surgery for evaluating the following features: proximal stump morphology, extent of occlusion, occlusion with collapse, arterial tortuosity, the presence of hyperintense signals (HIS) and calcification in the occluded C1 segment. Multivariate logistic regression was used to identify features associated with technical success and construct a prediction model. Results: Eighty-three patients were recruited, of which fifty-seven (68.7%) were recanalized successfully. The morphological and compositional characteristics of CICAO were associated with successful recanalization, including occlusions limited to C1 and extensive HIS, as well as the absence of extensive calcification, absence of high tortuosity, and absence of artery collapse. The MR CICAO score that comprised the five predictors showed a high predictive ability (area under the curve: 0.888, p < 0.001). Conclusion: the MR-VWI characteristics of CICAO predicted the technical success of endovascular recanalization and may be leveraged for identifying patients with a high probability of successful recanalization.

NF-κB represses retinoic acid receptor-mediated GPRC5A transactivation in lung epithelial cells to promote neoplasia.

Chronic inflammation is associated with lung tumorigenesis, in which NF-κB-mediated epigenetic regulation plays a critical role. Lung tumor suppressor G protein-coupled receptor, family C, member 5A (GPRC5A), is repressed in most non-small cell lung cancer (NSCLC); however, the mechanisms remain unclear. Here, we show that NF-κB acts as a transcriptional repressor in suppression of GPRC5A. NF-κB induced GPRC5A repression both in vitro and in vivo. Intriguingly, transactivation of NF-κB downstream targets was not required, but the transactivation domain of RelA/p65 was required for GPRC5A repression. NF-κB did not bind to any potential cis-element in the GPRC5A promoter. Instead, p65 was complexed with retinoic acid receptor α/ß (RARα/ß) and recruited to the RA response element site at the GPRC5A promoter, resulting in disrupted RNA polymerase II complexing and suppressed transcription. Notably, phosphorylation on serine 276 of p65 was required for interaction with RARα/ß and repression of GPRC5A. Moreover, NF-κB-mediated epigenetic repression was through suppression of acetylated histone H3K9 (H3K9ac), but not DNA methylation of the CpG islands, at the GPRC5A promoter. Consistently, a histone deacetylase inhibitor, but not DNA methylation inhibitor, restored GPRC5A expression in NSCLC cells. Thus, NF-κB induces transcriptional repression of GPRC5A via a complex with RARα/ß and mediates epigenetic repression via suppression of H3K9ac.

Extracellular vesicle long RNA markers of early-stage lung adenocarcinoma.

Lung cancer screening by low-dose computed tomography (LDCT) can improve mortality rates among high-risk individuals, especially adenocarcinoma cases with characteristically poor prognosis, although high false-positive rates have limited its clinical application. The objective of our study was to identify biomarkers for early-stage lung adenocarcinoma (ie, tumor diameter <2 cm) through extracellular vesicle long RNA (evlRNA) sequencing. High throughput evlRNA sequencing and support vector machine (SVM) identification of candidate diagnostic marker transcripts were performed using serum samples obtained before lung surgery. A total of 145 upregulated and 363 downregulated differential genes (P value <.05, fold change >1.5) were identified between lung adenocarcinoma (LUAD) patients and benign controls. An SVM model based on a 23-gene signature could distinguish EV samples of LUAD patients from those of control subjects with 86.49% sensitivity, 95.00% specificity and 92.31% accuracy in the training set and 93.75% sensitivity, 85.71% specificity and 88.24% accuracy in the validation set. A 17-gene signature was then identified that could distinguish AIS patient samples from those of MIA/IAD patients with 93.33% sensitivity, 98.00% specificity, and 96.25% accuracy in the trainingset and 83.33% sensitivity, 96.55% specificity, and 94.29% accuracy in the validation set. EvlRNAs in serum show considerable diagnostic value for screening LUAD patients with tumor sizes <2 cm in conjunction with LDCT, potentially reducing false positive rates while improving mortality rates.