Prognostic Marker For Lung Adenocarcinoma Research Articles

Regulation of overexpression lncRNA ATP2B1-AS1 on lung adenocarcinoma progression

BackgroundLncRNA ATP2B1-AS1 (ATP2B1-AS1) is involved in the occurrence and development of various diseases, while the relationship between lung adenocarcinoma (LUAD) and ATP2B1-AS1 is unclear. This study was to investigate the expression of ATP2B1-AS1 in LUAD and its influence on survival and prognosis of patients.MethodsLUAD tissue samples from patients participating in this study were collected, and the expression levels of ATP2B1-AS1 and miR-141-3p in LUAD sampleswere detected by real-time quantitative polymerase chain reaction (RT-qPCR). The effect of ATP2B1-AS1 on the growth of A549 cells was investigated through cell counting kit-8 (CCK-8) and transwell experiments. Besides, the prognostic value of ATP2B1-AS1 in LUAD was assessed via Kaplan-Meier curve and multivariate Cox regression.ResultsATP2B1-AS1 was downregulated in LUAD tissues and cells, whereas miR-141-3p was upregulated. After pcDNA3.1-ATP2B1-AS1 was transfected into A549 cells, the proliferation ability of A549 cells was decreased, and the migration level and invasion of A549 cells were also inhibited. High expression of ATP2B1-AS1 sponge miR-141-3p exerted prognostic value.ConclusionsATP2B1-AS1 sponge miR-141-3p alleviated the progression of LUAD, and ATP2B1-AS1 may be deemed as a prognostic marker for LUAD.

CircSFMBT2 Plays an Oncogenic Role in Lung Adenocarcinoma Depending on the miR-1305/SALL4 Axis.

Circular RNAs (circRNAs) exhibit significant functions in diverse malignant tumors, including lung adenocarcinoma (LUAD). In this study, we aimed to elucidate the role of circRNA scm like with four mbt domains 2 (circSFMBT2) in LUAD. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot assay or immunohistochemistry (IHC) assay was performed for quantification of circSFMBT2, microRNA-1305 (miR-1305), spalt like transcription factor 4 (SALL4), proliferating Cell Nuclear Antigen (PCNA) or Ki-67. 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assay and flow cytometry analysis were applied to analyze cell proliferation, metastasis and apoptosis, respectively. Mouse xenograft model was established to explore the function of circSFMBT2. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to estimate the relationship between miR-1305 and circSFMBT2 or SALL4. CircSFMBT2 was upregulated in LUAD and related to advanced TNM stage and poor prognosis. CircSFMBT2 knockdown suppressed cell proliferation, metastasis, glycolysis and induced apoptosis in LUAD cells in vitro as well as tumor formation in vivo. CircSFMBT2 directly targeted miR-1305, and miR-1305 inhibition reversed circSFMBT2 knockdown-mediated inhibitory effects on LUAD malignant behaviors. SALL4 was the target gene of miR-1305. MiR-1305 overexpression repressed the malignant phenotypes of LUAD cells, while SALL4 enhancement abated the effects. CircSFMBT2 aggravated the progression of LUAD by the miR-1305/SALL4 axis, which might provide a diagnostic and prognostic marker for LUAD.

Unraveling SARS-CoV-2-associated lncRNAs' prognostic significance in lung adenocarcinoma-survival, immunity, and chemotherapy responses

BackgroundThis study investigates the link between SARS-CoV-2-associated long non-coding RNAs (lncRNAs) and lung adenocarcinoma (LUAD). LUAD is a prevalent and aggressive lung cancer type. The study aims to identify prognostic lncRNAs and construct a predictive model while shedding light on potential therapeutic targets during the COVID-19 era. ResultsEight SARS-CoV-2-associated lncRNAs with significant prognostic value in LUAD were identified, forming a robust prognostic risk model. The model exhibited strong predictive performance, with high area under the ROC curve (AUC) values at one, three, and five years. Furthermore, the risk score was an independent prognostic factor, correlating with the cancer stage. Notably, differences in immune function, drug sensitivity, and immune checkpoint expression were observed between high- and low-risk groups. ConclusionsThis study unveils eight SARS-CoV-2-associated lncRNAs as valuable prognostic markers in LUAD, yielding a reliable prognostic risk model. Additionally, the model's ability to predict patient outcomes and its correlation with cancer stage underscores its clinical utility. The observed variances in immune function, drug sensitivity, and immune checkpoint expression suggest potential avenues for personalized LUAD treatment strategies. Clinicians can utilize the prognostic risk model to predict LUAD patient outcomes, informing treatment decisions. The insights into immune function, drug sensitivity, and immune checkpoints offer opportunities for tailored therapies, potentially enhancing patient outcomes. This study underscores the importance of considering the interplay between SARS-CoV-2-associated factors and cancer biology, especially in the context of the COVID-19 pandemic.How to cite: Zhou Q, Yuan T, Xie Z, et al. Unraveling SARS-CoV-2-associated lncRNAs' prognostic significance in lung adenocarcinoma-survival, immunity, and chemotherapy responses. Electron J Biotechnol 2024;67. https://doi.org/10.1016/j.ejbt.2023.10.001.

Role of Prognostic Marker PRR11 in Immune Infiltration for Facilitating Lung Adenocarcinoma Progression

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.

Erythropoietin receptor is a risk factor for prognosis: A potential biomarker in lung adenocarcinoma

Lung cancer has the highest mortality rate of all cancers, and LUAD's survival rate is particularly poor. Erythropoietin receptor (EPOR) can be detected in lung adenocarcinoma (LUAD), however, the expression levels and prognostic value of EPOR in LUAD are still unclear. In our study, clinicopathological data of 92 LUAD patients between January 2008 and June 2016, multiple bioinformatics databases and immunohistochemistry were used to explore the EPOR expression, the mutant genes affecting EPOR expression, and the correlation of EPOR expression with oxidative stress - related genes, prognosis, immune microenvironment. All statistical analyses were performed in the R version 4.1.1. The study found that EPOR expression might be down-regulated at the mRNA levels and significantly up-regulated at the protein levels in LUAD, which indicates that the mRNA and protein levels of EPOR are inconsistent. The muTarget showed that the expression of EPOR was significantly different between the mutant group and the wild group of 15 genes, including DDX60L and C1orf168. Importantly, we found that EPOR was associated with VEGF and HIF family members, and had significant positive correlation with oxidative stress - related genes such as CCS, EPX and TXNRD2. This suggests that EPOR may be involved in the regulation of oxidative stress. The Kaplan-Meier Plotter and PrognoScan databases consistently concluded that EPOR was associated with prognosis in LUAD patients. Our clinicopathological data showed that high EPOR expression was associated with poorer overall survival (29.5 vs 46 months) and had a good predictive ability for 4-year and 5-year survival probability. EPOR is expected to be a potential new prognostic marker for LUAD.

Identification of TLRs as potential prognostic biomarkers for lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most common tumors with the highest cancer-related death rate worldwide. Early diagnosis of LUAD can improve survival. Abnormal expression of the Toll-like receptors (TLRs) is related to tumorigenesis and development, inflammation and immune infiltration. However, the role of TLRs as an immunotherapy target and prognostic marker in lung adenocarcinoma is not well understood and needs to be analyzed. Relevant data obtained from databases such as ONCOMINE, UALCAN, GEPIA, and the Kaplan-Meier plotter, GSCALite, GeneMANIA, DAVID 6.8, Metascape, LinkedOmics and TIMER, to compare transcriptional TLRs and survival data of patients with LUAD. The expression levels of TLR1/2/3/4/5/7/8 in LUAD tissues were significantly reduced while the expression levels of TLR6/9/10 were significantly elevated. LUAD patients having low expression of TLR1/2/3/5/8 and high expression of TLR9 had a poor overall survival while patients with low expression of TLR2/3/7 presented with worse first progress. TLR4, TLR7 and TLR8 are the 3 most frequently mutated genes in the TLR family. Correlation suggested a low to moderate correlation among TLR family. TLR family was also involved in the activation or inhibition of the famous cancer related pathways. Analysis of immune infiltrates analysis suggested that TLR1/2/7/8 levels significantly correlated with immune infiltration level. Enrichment analysis revealed that TLRs were involved in TLR signaling pathway, immune response, inflammatory response, primary immunodeficiency, regulation of IL-8 production and PI3K-Akt signaling pathway. Our results provided information on TLRs expression and potential regulatory networks in LUAD. Moreover, our results suggested TLR2/7/8 as a potential prognostic biomarker for lung adenocarcinoma.

Lysosome-related genes: A new prognostic marker for lung adenocarcinoma.

Currently, a reliable early prognostic marker has not been identified for lung adenocarcinoma (LUAD), the most common malignancy. Recent studies demonstrated that lysosomal rupture is involved in cancer migration, progression, and immune microenvironment formation. We performed a bioinformatics analysis of lysosomal rupture to investigate whether lysosome-related genes (LRGs) are key in LUAD. The analysis identified 23 LRGs. Cytoscape visualization identified 10 core genes (CCNA2, DLGAP5, BUB1B, KIF2C, PBK, CDC20, NCAPG, ASPM, KIF4A, ANLN). With the 23 LRGs, we established a new risk scoring rule to classify patients with LUAD into high- and low-risk groups and verified the accuracy of the risk score by receiver operating characteristic curves and established a nomogram to evaluate clinical patients. Immunotherapy effectiveness between the high- and low-risk groups was evaluated based on the tumor mutational burden and analyses of immune cell infiltration and drug sensitivity. Pathway enrichment analysis revealed that lysosomes were closely associated with glucose metabolism, amino acid metabolism, and the immune response in patients with LUAD. Lysosomes are a likely new therapeutic target and provide new directions and ideas for treating and managing patients with LUAD.

Granzyme B (GZMB)-Positive Tumor-Infiltrating Lymphocytes in Lung Adenocarcinoma: Significance as a Prognostic Factor and Association with Immunosuppressive Proteins.

Granzyme B (GZMB) is a serine protease produced by cytotoxic lymphocytes that reflects the activity of anti-tumor immune responses in tumor-infiltrating lymphocytes (TILs); however, the prognostic significance of GZMB+ TILs in lung adenocarcinoma is poorly understood. We analyzed 273 patients with pathological stage (pStage) I-IIIA lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We evaluated GZMB+ TIL counts by immunohistochemistry. We set the cut-off values at 12cells/0.04mm2 for GZMB+ TILs and divided the patients into GZMB-High (n=171) and GZMB-Low (n=102) groups. Then, we compared the clinicopathological characteristics of the two groups and clinical outcomes. Programmed cell death ligand-1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression in tumor cells was also evaluated, and combined prognostic analyses of GZMB+ TILs with PD-L1 or IDO1 were performed. GZMB-Low was significantly associated with pStage II-III, PD-L1 positivity, and IDO1 positivity. Disease-free survival (DFS) and overall survival (OS) in the GZMB-Low group were significantly worse than in the GZMB-High group. In multivariable analysis, GZMB-Low was an independent prognostic factor for both DFS and OS. Furthermore, combined prognostic analyses of GZMB+ TILs with PD-L1 or IDO1 showed that GZMB-Low with high expression of these immunosuppressive proteins had the worst prognosis. We analyzed GZMB+ TIL counts in lung adenocarcinoma and elucidated its prognostic significance and association with PD-L1 and IDO1. GZMB+ TIL counts might reflect the patient's immunity against cancer cells and could be a useful prognostic marker of lung adenocarcinoma.

Dipeptidase‑2 is a prognostic marker in lung adenocarcinoma that is correlated with its sensitivity to cisplatin.

Lung cancer accounts for the highest percentage of cancer morbidity and mortality worldwide, and lung adenocarcinoma (LUAD) is the most prevalent subtype. Although numerous therapies have been developed for lung cancer, patient prognosis is limited by tumor metastasis and more effective treatment targets are urgently required. In the present study, gene expression profiles were extracted from the Gene Expression Omnibus database and mRNA expression data were downloaded from The Cancer Genome Atlas database. In addition, TIMER 2.0 database was used to analyze the expression of genes in normal and multiple tumor tissues. Protein expression was confirmed using the Human Protein Atlas database and LUAD cell lines, sphere formation assay, western blotting, and a xenograft mouse model were used to confirm the bioinformatics analysis. Dipeptidase‑2 (DPEP2) expression was significantly decreased in LUAD and was negatively associated with prognosis. DPEP2 overexpression substantially inhibited epithelial‑mesenchymal transition (EMT) as well as LUAD cell metastasis, and limited the expression of the cancer stem cell transformation markers, CD44 and CD133. In addition, DPEP2 improved LUAD sensitivity to cisplatin by inhibiting EMT; this was verified invitro and invivo. These data indicated that DPEP2 upregulates E‑cadherin, thereby regulating cell migration, cancer stem cell transformation, and cisplatin resistance, ultimately affecting the survival of patients with LUAD. Overall, the findings of the present suggest that DPEP2 is important in the development of LUAD and can be used both as a prognostic marker and a target for future therapeutic research.

EVI2B may be a novel prognostic marker for lung adenocarcinoma.

Objective: This study intended to unravel the relationship of EVI2B expression with lung adenocarcinoma (LUAD). Methods: TIMER1.0, Gene Expression Profiling Interactive Analysis and Human Protein Atlas databases, as well as the University of Alabama at Birmingham Cancer website, were used to analyze the expression of EVI2B and its relationship with clinical features. The relationship between survival curve analysis and prognosis was analyzed. The role of EVI2B in LUAD was verified by wet experiments. Results: EVI2B was markedly downregulated in LUAD. There was a relationship between the expression of EVI2B and clinical features. Low EVI2B level was substantially implicated in low survival in LUAD. EVI2B overexpression constrained LUAD cell viability, migration and invasion. Conclusion: EVI2B was related to prognosis and immune microenvironment in LUAD, suggesting that EVI2B may be a novel prognostic marker for LUAD.

The prognostic effect of ADH1B and ALDH2in lung adenocarcinoma.

e15167 Background: Alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) are major enzymes involved in the metabolism of carcinogenic acetaldehyde, converting alcohol to acetaldehyde and detoxifying acetaldehyde to harmless acetic acid, respectively. To investigate the role of ADH isoenzymes and ALDH isoenzymes in the development of lung adenocarcinoma (LUAD), we performed a retrospective analysis of gene expression. Methods: RNA sequencing data derived from 497 tumour samples and 54 adjacent normal samples were obtained from the Cancer Genome Atlas (TCGA) database. The transcript levels of ADH and ALDH family genes were compared between tumour tissue and adjacent normal tissue through a Wilcoxon test. The results were validated in transcriptomic data from 111 lung cancer patients available as part of a prior study. The diagnostic and prognostic value of ADH and ALDH family genes was further investigated by survival analysis and nomogram through the TCGA database. Insights into the mechanism of action were gained through gene set enrichment analysis (GSEA). Results: Numerous ADH and ALDH family genes showed nominally significant differential expression between tumour and adjacent normal tissues. The expression levels of ADH1B and ALDH2 showed significant and replicable depression in tumour tissue. Low expression of ADH1B and ALDH2 was associated with worse overall survival, with the combination of these genes providing greater prognostic value than the additive effects of these genes individually in the TCGA database. ADH1B and ALDH2 transcript levels were linked with the regulation of metabolism, cell cycle, DNA repair and cancer-associated pathways. A risk score model for predicting LUAD prognosis was developed and showed good performance in predicting 1, 3 and 5-year overall survival (OS). Consistent with TCGA results, our 111-patient replication dataset showed that the tumour-specific depression was most pronounced for ADH1B, and the lower expression was associated with vascular, pleural and lymphatic invasions. Moreover, smoking status and/or cumulative smoking history do not provide a direct, clinically accessible proxy for tumour ADH1B or ALDH2 expression. Conclusions: The combination of ADH1B and ALDH2 are potential prognostic markers in LUAD and may have utility as an independent clinical factor for evaluating the prognosis of LUAD.

Identification of GPD1L as a Potential Prognosis Biomarker and Associated with Immune Infiltrates in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most prevalent pathological kinds of lung cancer, which is a common form of cancer that has a high death rate. Over the past several years, growing studies have indicated that GPD1L was involved in the advancement of a number of different cancers. However, its clinical significance in LUAD has not been investigated. In this study, following an examination of the TGCA datasets, we found that GPD1L displayed a dysregulated state in a wide variety of cancers; this led us to believe that GPD1L is an essential regulator in the progression of malignancies. In addition, we found that the expression of GPD1L was much lower in LUAD tissues when compared with nontumor specimens. According to the findings of ROC tests, GPD1L was able to effectively identify LUAD specimens from nontumor samples with an AUC value of 0.828 (95% confidence interval: 0.793 to 0.863). On the basis of the clinical study, a low expression of GPD1L was clearly related with both the N stage and the clinical stage. Moreover, based on the findings of a Kaplan-Meier survival study, elevated GPD1L expression was a strong indicator of considerably improved overall survival (OS) and disease-specific survival (DSS). GPD1L expression and clinical stages were found to be independent prognostic indicators for overall survival and disease-free survival in LUAD patients, according to multivariate analyses. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram demonstrated an effective prediction performance for LUAD patients. Besides, the expression of GPD1L was positively related to mast cells, eosinophils, Tcm, TFH, iDC, DC, and macrophages, while negatively associated with Th2 cells, NK CD56dim cells, Tgd, Treg, and neutrophils. Finally, qRT-PCR was able to demonstrate that GPD1L had a significant amount of expression in LUAD. Additionally, according to the results of functional tests, overexpression of GPD1L had a significant inhibiting effect on the proliferation of LUAD cells. In general, the results of our study suggested that GPD1L had the potential to serve as a diagnostic and prognostic marker for LUAD.

Identification of four metabolic subtypes and key prognostic markers in lung adenocarcinoma based on glycolytic and glutaminolytic pathways

BackgroundGlucose and glutamine are the main energy sources for tumor cells. Whether glycolysis and glutaminolysis play a critical role in driving the molecular subtypes of lung adenocarcinoma (LUAD) is unknown. This study attempts to identify LUAD metabolic subtypes with different characteristics and key genes based on gene transcription profiling data related to glycolysis and glutaminolysis, and to construct prognostic models to facilitate patient outcome prediction.MethodsLUAD related data were obtained from the Cancer Genome Atlas and Gene Expression Omnibus, including TCGA-LUAD, GSE42127, GSE68465, GSE72094, GSE29013, GSE31210, GSE30219, GSE37745, GSE50081. Unsupervised consensus clustering was used for the identification of LUAD subtypes. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and CytoNCA App in Cytoscape 3.9.0 were used for the screening of key genes. The Cox proportional hazards model was used for the construction of the prognostic risk model. Finally, qPCR analysis, immunohistochemistry and immunofluorescence colocalization were used to validate the core genes of the model.ResultThis study identified four distinct characterized LUAD metabolic subtypes, glycolytic, glutaminolytic, mixed and quiescent types. The glycolytic type had a worse prognosis than the glutaminolytic type. Nine genes (CXCL8, CNR1, AGER, ALB, S100A7, SLC2A1, TH, SPP1, LEP) were identified as hub genes driving the glycolytic/glutaminolytic LUAD. In addition, the risk assessment model constructed based on three genes (SPP1, SLC2A1 and AGER) had good predictive performance and could be validated in multiple independent external LUAD cohorts. These three genes were differentially expressed in LUAD and lung normal tissues, and might be potential prognostic markers for LUAD.ConclusionLUAD can be classified into four different characteristic metabolic subtypes based on the glycolysis- and glutaminolysis-related genes. Nine genes (CXCL8, CNR1, AGER, ALB, S100A7, SLC2A1, TH, SPP1, LEP) may play an important role in the subtype-intrinsic drive. This metabolic subtype classification, provides new biological insights into the previously established LUAD subtypes.

CDC25C Protein Expression Correlates with Tumor Differentiation and Clinical Outcomes in Lung Adenocarcinoma

Given that, even after multimodal therapy, early-stage lung cancer (LC) often recurs, novel prognostic markers to help guide therapy are highly desired. The mRNA levels of cell division cycle 25C (CDC25C), a phosphatase that regulates G2/M cell cycle transition in malignant cells, correlate with poor clinical outcomes in lung adenocarcinoma (LUAD). However, whether CDC25C protein detected by immunohistochemistry can serve as a prognostic marker in LUAD is yet unknown. We stained an LC tissue array and a cohort of 61 LUAD tissue sections for CDC25C and searched for correlations between CDC25C staining score and the pathological characteristics of the tumors and the patients' clinical outcomes. Clinical data were retrieved from our prospectively maintained departmental database. We found that high expression of CDC25C was predominant among poorly differentiated LUAD (p < 0.001) and in LUAD > 1cm (p < 0.05). Further, high expression of CDC25C was associated with reduced disease-free survival (p = 0.03, median follow-up of 39 months) and with a trend for reduced overall survival (p = 0.08). Therefore, high expression of CDC25C protein in LUAD is associated with aggressive histological features and with poor outcomes. Larger studies are required to further validate CDC25C as a prognostic marker in LUAD.

NCAPD2 is a novel marker for the poor prognosis of lung adenocarcinoma and is associated with immune infiltration and tumor mutational burden.

Lung adenocarcinoma (LUAD) is at present the most prevalent subtype of lung cancer worldwide. Non-SMC condensin I complex subunit D2 (NCAPD2) is one of the 3 non-SMC subunits in condensin I. Previous studies have confirmed that NCAPD2 plays a critical role in chromosome cohesion and segregation. NCAPD2 may be involved in tumorigenesis and progression by participating in abnormal cell cycle division, but the prognostic value of NCAPD2 in LUAD remains unclear. We investigated differences in the expression levels of NCAPD2 and determined their association with clinical features, as well as their diagnostic and prognostic value using the cancer genome atlas database. The function of NCAPD2 was analyzed using gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis. CIBERSORT, single-sample gene set enrichment analysis, and ESTIMATE were used to analyze the immune microenvironment of tumor patients. Tumor mutational burden (TMB) and immune checkpoints were analyzed, while hub genes were identified using weighted gene coexpression network analysis and were used to construct prognostic models. Subsequently, the competing endogenous RNAs network of NCAPD2 in LUAD was explored. Finally, we performed qPCR to verify differences in NCAPD2 expression between the tumor and normal tissues. The expression of NCAPD2 in LUAD was significantly upregulated compared with normal lung tissues. NCAPD2 has been linked to the T stage, N stage, and tumor stage. The elevated expression of NCAPD2 in LUAD can predict a poor prognosis. Functional enrichment analysis indicated that the main function of NCAPD2 was in cell cycle regulation. Moreover, NCAPD2 was also associated with immune cell infiltration and TMB. NCAPD2 is a novel prognostic marker in LUAD and is associated with immune infiltration and TMB.

Leukocyte CH25H is a potential diagnostic and prognostic marker for lung adenocarcinoma

Metastasis, a major challenge during the treatment of lung cancer, causes deterioration in patient health outcomes. Thus, to address this problem, this study aimed to explore the role and contribution of Cholesterol 25-Hydroxylase (CH25H) as a potential diagnostic and prognostic marker in lung cancer. Online public databases were used to analyze the expression level, prognostic value, gene-pathway enrichment, and immune infiltration of CH25H in lung cancer patients. The Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to analyze and detect the CH25H expression levels in leukocytes from lung cancer patients. The expression level of CH25H was significantly reduced in lung adenocarcinoma (LUAD), which is associated with a higher disease stage, but not in lung squamous cell carcinoma (LUSC). Kaplan–Meier survival analysis indicated that LUAD patients with low CH25H expression had a worse prognosis. Mechanistically, our results showed that in LUAD, CH25H may be a regulatory factor affecting the immune cell infiltration level, and the resultant tumor development. Experimental data showed that low expression of CH25H in leukocytes was significantly associated with LUAD metastasis (P < 0.01). Our study suggests that CH25H may function as a prognostic and risk stratification biomarker for LUAD.

Correlation between oncogene integrator complex subunit 7 and a poor prognosis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most common types of cancer worldwide with high incidence and mortality rates. The integrator complex subunit 7 (INTS7) encodes a subunit of the integrator complex that mediates small-nuclear ribonucleic acid (RNA) processing and has been shown to be associated with RNA polymerase II. However, the clinical significance of INTS7 in LUAD is still not clear and needs to be investigated. The single-cell sequencing of a publicly available data set was conducted to compare the expression levels and percentages of INTS7 in lung malignant cells at different classifications and stages. Further, 33 cancer types from The Cancer Genome Atlas (TCGA) database were analyzed, protein-protein interaction (PPI) networks were constructed, and functional annotations were undertaken for the INTS7 gene. INTS7 small-interfering RNAs were transfected into LUAD cell lines, and cell biological behaviors, such as migration, invasion, apoptosis and proliferation capacity, were then examined. We found that the expression of INTS7 was significantly more upregulated in the LUAD tissues than the adjacent normal tissues. Increased INTS7 messenger RNA expression was correlated with TNM (tumor node metastasis classification) stage and gender in LUAD patients. Further, the Kaplan-Meier survival analysis indicated that LUAD patients with high INTS7 expression levels had a worse prognosis than those with low INTS7 expression levels. Finally, we found that silencing INTS7 inhibited LUAD cell viability and invasion in vitro. These results suggest that INTS7 can be used as a potential therapy target and prognostic marker for LUAD. Further, INTS7 may aggravate migration and invasion, induce the proliferation, and attenuate the apoptosis capacity of cells in LUAD.

The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis

Brain metastasis occurs in approximately 30% of patients with lung adenocarcinoma (LUAD) and is closely associated with poor prognosis, recurrence, and death. However, dynamic gene regulation and molecular mechanism driving LUAD progression remain poorly understood. In this study, we performed a comprehensive single-cell transcriptome analysis using data from normal, early stage, advanced stage, and brain metastasis LUAD. Our single-cell-level analysis reveals the cellular composition heterogeneity at different stages during LUAD progression. We identified stage-specific risk genes that could contribute to LUAD progression and metastasis by reprogramming immune-related and metabolic-related functions. We constructed an early advanced metastatic dysregulated network and revealed the dynamic changes in gene regulations during LUAD progression. We identified 6 early advanced (HLA-DRB1, HLA-DQB1, SFTPB, SFTPC, PLA2G1B, and FOLR1), 8 advanced metastasis (RPS15, RPS11, RPL13A, RPS24, HLA-DRB5, LYPLA1, KCNJ15, and PSMA3), and 2 common risk genes in different stages (SFTPD and HLA-DRA) as prognostic markers in LUAD. Particularly, decreased expression of HLA-DRA, HLA-DRB1, HLA-DQB1, and HLA-DRB5 refer poor prognosis in LUAD by controlling antigen processing and presentation and Tcell activation. Increased expression of PSMA3 and LYPLA1 refer poor prognosis by reprogramming fatty acid metabolism and RNA catabolic process. Our findings will help further understanding the pathobiology of brain metastases in LUAD.

Prognostic impact of tumor microenvironment-related markers in patients with adenocarcinoma of the lung

Cancer-associated fibroblasts (CAFs) are a prominent component in the tumor microenvironment (TME), which plays an important role in lung carcinogenesis. Here, we investigated microenvironmental markers expressed by CAFs, including α-smooth muscle actin, CD10, podoplanin, fibroblast-specific protein 1, platelet-derived growth factor α and β, fibroblast-associated protein, tenascin-C, zinc finger E-box binding homeobox 1 (ZEB1), and twist-related protein 1 expression levels. We evaluated samples from 257 patients with lung adenocarcinoma (LAD) to assess the associations of CAF-related protein expression patterns with prognosis. LAD cases were stratified using cluster analysis. To determine the utility of prognostic markers in LAD, univariate and multivariate analyses were performed. LAD cases were classified into subgroups 1 and 2. Subgroup 2 was shown to be significantly correlated with disease-free and overall survival using univariate and multivariate analyses in this group. Upregulation of podoplanin was identified as a single prognostic marker in this study by univariate and multivariate analyses. In addition, ZEB1 overexpression was correlated with disease-free survival. Our current results suggested that the specific CAF phenotype (e.g., the expression pattern of CAF-related proteins) could predict outcomes in patients with LAD. In addition, podoplanin upregulation may predict outcomes in these patients.

Low expression of INMT is associated with poor prognosis but favorable immunotherapy response in lung adenocarcinoma.

Background: The expression of INMT (indolethylamine N-methyltransferase) has been reported to be downregulated in non-small-cell lung cancer (NSCLC). However, the role of INMT in NSCLC remains elusive. We aim to investigate the underlying mechanisms and clinical value of INMT in NSCLC, especially in lung adenocarcinoma (LUAD). Methods: Gene expression cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess the effect of INMT on NSCLC. Gene expression data from an immunotherapy cohort were used to investigate the association of INMT with immunotherapy in NSCLC. Results: INMT expression was significantly downregulated in NSCLC compared with adjacent normal tissues. Downregulated INMT was associated with poor overall survival in LUAD, but not in lung squamous carcinoma. Multivariate Cox regression analysis suggested that INMT was an independent prognostic marker in LUAD. INMT had a reference value in the diagnosis and prognostic estimation of LUAD. Gene set enrichment analysis showed that pathways of the cell cycle and DNA damage response were enriched in the INMT low-expression group. The top 10 hub genes upregulated in the INMT low-expression group mainly activated the cell cycle pathway. In addition, more frequently mutated TP53 genes, higher aneuploidy scores, a fraction of genomes altered, MANTIS scores, and tumor mutation burden were found in tumors with low expression of INMT. Furthermore, patients with low expression of INMT showed favorable clinical benefits to anti-PD-1 treatment with higher enrichment scores of immune-related signatures. Conclusion: The low expression of INMT was associated with poor prognosis but favorable immunotherapy response in LUAD. INMT may affect the progression of LUAD by regulating the cell cycle and may serve as a valuable independent prognostic biomarker in patients with LUAD.