Prognostic Marker In Lung Cancer Research Articles

Exosomal microRNAs in lung cancer: a narrative review.

Exosomes are nanoscale extracellular vesicles secreted by cells, which can release bioactive macromolecules, such as microRNA (miRNA) to receptor cells. Exosomes can efficiently penetrate various biological barriers which mediate intercellular communication. MiRNA are a class of non-coding RNA that primarily regulate messenger RNA (mRNA) at the post-transcriptional level. MiRNA is abundant in exosomes, which plays an important role by being transported and released through exosomes secreted by lung cancer cells. This review aims to elucidate the roles of exosome-derived miRNAs in lung cancer. We focused on the roles of exosome-derived miRNAs in cancer occurrence and development, including angiogenesis, cell proliferation, invasion, metastasis, immune escape, drug resistance, and their clinical value as new diagnostic and prognostic markers for lung cancer. Exosomal miRNA can not only affect angiogenesis of lung cancer, induce epithelial-mesenchymal transformation, and promote reprogramming of tumor microenvironment, but also affect immune regulation and drug resistance transmission and participate in regulating lung cancer cell proliferation. Therefore, understanding the regulatory roles of exosomal miRNAs in tumor invasion and metastasis can provide new ideas for the treatment of lung cancer. Exosomal miRNA can provide some unique ideas on how to improve the efficiency of diagnosis and treatment of lung cancer in the future. Targeting tumor-specific exosomal miRNA represents a new strategy for clinical treatment of lung cancer, which can provide potential non-invasive biomarkers in the early diagnosis of lung cancer. Investigation of the involvement of exosomal miRNAs in the occurrence and progression of tumors can yield new opportunities for the clinical diagnosis and treatment of lung cancer.

The impact of alpha-1 antitrypsin deficiency alleles on lung cancer survival.

Different studies have shown that carrying an alpha-1 antitrypsin (AAT) deficiency allele is an independent risk factor for developing lung cancer (LC). However, to date, little is known regarding whether carrying a deficiency allele may be a prognostic factor in the evolution of LC. A prospective observational study was carried out which consecutively included patients diagnosed with LC in University Hospital "Nuestra Señora de Candelaria" between December 2017 and August 2020. A blood sample was taken from each of the patients in order to determine both AAT serum concentration and genotype. Based on AAT genotype, patients were divided into the deficiency (Pi*≠MM) or non-deficiency (Pi*=MM) group. One hundred and sixty-four patients were included. The average length of follow-up was 13±10 months. Patients were classified as stage I (4.2%), stage II (8.3%), stage III (31.2%) and stage IV (56.3%), according to tumour, node and metastasis (TNM) staging. Twenty-eight patients (17%) were carriers of a deficiency allele (6 Pi*MS, 1 Pi*MZ, 1 Pi*MMheerlen). No significant differences were found with respect to baseline characteristics between Pi*≠MM and Pi*=MM. Patients in the Pi*≠MM group had a higher risk of death in the first 6 months after the LC diagnosis compared to Pi*=MM subjects (HR =2.04; 95% CI: 1.04-4.0; P=0.038). The presence of an AAT deficiency genotype could be a potential prognostic marker in LC. However, larger studies that justify these findings are needed.

Impact of KIF4A on Cancer Stem Cells and EMT in Lung Cancer and Glioma

Kinesin family member 4A (KIF4A) belongs to the kinesin 4 subfamily of kinesin-related proteins and is involved in the regulation of chromosome condensation and segregation during mitotic cell division. The expression of KIF4A in various types of cancer, including lung, breast, and colon cancer, has been found to be associated with poor prognosis in cancer patients. However, the exact mechanism by which it promotes tumorigenesis is not yet understood. In osteosarcoma, the expression of KIF4A has been shown to be associated with cancer stem cells (CSCs), whereas in breast cancer, it is not associated with the maintenance of CSCs but regulates the migratory ability of cells. In this light, we identified phenotypic phenomena affecting the malignancy of cancer in lung cancer and glioma, and investigated the mechanisms promoting tumorigenesis. As a result, we demonstrated that KIF4A affected lung cancer stem cells (LCSCs) and glioma stem cells (GSCs) and regulated CSC signaling mechanisms. In addition, the migratory ability of cells was regulated by KIF4A, and epithelial-to-mesenchymal transition (EMT) marker proteins were controlled. KIF4A regulated the expression of the secretory factor plasminogen activator inhibitor-1 (PAI-1), demonstrating that it sustains cancer malignancy through an autocrine loop. Taken together, these findings suggest that KIF4A regulates CSCs and EMT, which are involved in cancer recurrence and metastasis, indicating its potential value as a novel therapeutic target and prognostic marker in lung cancer and glioma.

B-365 Serum MAGE-A3 and MAGE-A4 Protein Levels as Potential Prognostic Biomarkers for Lung Cancer

Abstract Background Melanoma-associated antigen 3 (MAGE-A3) and MAGE-A4 are members of Melanoma Antigen Gene (MAGE) family, which have restricted expression to the testis and are abnormally expressed in cancer cells. MAGE-A3 and MAGE-A4 are overexpressed in lung cancer and have been shown to be associated with cancer progression and poor prognosis. Elevated MAGE-A4 protein level in lung cancer serum samples has been reported in the literature, however, it is unclear whether MAGE-A3 protein can be detected in serum samples of lung cancer patients. Methods We developed human MAGE-A3 and MAGE-A4 sandwich ELISA kits and used them to measure serum MAGE-A3 and MAGE-A4 protein levels in 21 lung cancer patients and 30 non-cancer controls. Results Serum MAGE-A3 protein was detected in all 21 lung cancer patients (range: 34 to 78871 pg/mL, mean: 5600 pg/mL) and was significantly elevated compared to non-cancer controls (range: 23–308 pg/mL, mean: 140 pg/mL) (P < 0.05). Serum MAGE-A4 protein was detected in 5 of 21 (24%) lung cancer patients (range: 280 to 35096 pg/mL, mean: 1819 pg/mL), and the samples with high serum MAGE-A4 concentration matched those with high serum MAGE-A3 concentration. Serum MAGE-A4 protein was not detectable in non-cancer controls. Conclusion Our findings suggest that serum MAGE-A3 and MAGE-A4 may serve as potential prognostic biomarkers for lung cancer. The detection of elevated serum MAGE-A3 and MAGE-A4 in lung cancer patients indicates their specificity for the disease. Larger studies with more samples, different cancer stages, and longer follow-up are needed to validate these results and establish the clinical utility of serum MAGE-A3 and MAGE-A4 levels as prognostic markers for lung cancer. If further validated, these biomarkers could aid in early diagnosis and better management of lung cancer.

Exploration of selected monoterpenes as potential TRPC channel family modulator in lung cancer, an in-silico upshot

Lung cancer is still the most frequent cause of cancer-related death, accounting for nearly two million cases yearly. As cancer is a multifactorial disease, developing novel molecular therapeutics that can simultaneously target multiple associated cellular processes has become necessary. Ion channels are diverse regulators of cancer-related processes such as abnormal proliferation, invasion, migration, tumor progression, inhibition of apoptosis, and chemoresistance. Among the various families of ion channels, the transient receptor potential canonical channel family steps out in the context of lung cancer, as several members have been postulated as prognostic markers for lung cancer. Phytochemicals have been found to have health benefits in the treatment of a variety of diseases and disorders. Among phytochemicals, monoterpenes are effective in treating both the early and late stages of cancer. The molecular docking interaction analysis was conducted to evaluate the binding potential of selected monoterpenes with TRPC3, TRPC4, TRPC5, and TRPC6 involved in different phases of carcinogenesis. Amongst the selected monoterpenes, thymoquinone exhibited the highest binding energy of −6.7 kcal/mol against the TRPC4 channel, and all amino acid binding residues were similar to those of the known inhibitor for TRPC4. In addition, molecular-dynamic simulation results parameters, such as RMSD, RMSF, and Rg, indicated that thymoquinone did not impact the protein compactness and exhibited stability during the interaction. The average interaction energy between thymoquinone and TRPC4 protein was −26.85 kJ/mol. In-silico Drug-likeness and ADMET profiling indicated that thymoquinone is a druggable candidate with minimal toxicity. We propose further investigation and evaluation of thymoquinone for lead optimization and drug development. Communicated by Ramaswamy H. Sarma

Circular RNAs as biomarkers for lung cancer

Lung cancer is the leading cause of death and morbidity from malignant neoplasms worldwide, and its poor prognosis places a heavy burden on patients. A large percentage of lung cancer cases are associated with smoking. A significant number of non-smokers also develop the disease, suggesting an epigenetic and genetic mechanism for the development of lung cancer. The current situation with the diagnosis and treatment of lung cancer remains grim, and effective therapeutic targets and molecular markers are urgently needed. Circular RNAs (circRNAs) are covalently closed non-coding RNAs that have received much attention due to their biological properties such as conservatism, stability, and tissue specificity. Many studies have shown that circRNAs are involved in the regulation of lung cancer through various mechanisms, such as microRNA adsorption, and play an important role in the early diagnosis, treatment, and prognosis of lung cancer. In recent years, it has become increasingly clear that circRNAs are involved in the proliferation, migration, and invasion of lung cancer cells. Differentially expressed circRNAs can be used as non-invasive diagnostic and prognostic markers of lung cancer. This article summarizes the current advances of circRNAs in the diagnosis, treatment and prognosis of lung cancer.

Pretreatment Platelet Count is a Prognostic Marker in Lung Cancer: A Danish Registry-based Cohort Study

BackgroundThrombocytosis has been associated with a poor prognosis in a wide range of malignancies. However, the results have been conflicting for lung cancer. Therefore, we evaluated the prognostic value of platelet count in a large cohort of lung cancer patients. Patients and MethodsAll lung cancer patients diagnosed in The Central Denmark Region from 2009 to 2018 were included in the study. Data from the Danish Lung Cancer Registry were combined with data from the clinical laboratory information system on pretreatment platelet count. Platelet count was defined as low, normal, or high based on being below, within, or above the reference intervals. The prognostic value of platelet count was assessed by the Cox proportional hazard model. C-statistics were conducted to investigate if the platelet count added additional prognostic value to existing prognostic markers. ResultsTotally, 6,758 patients with non–small-cell lung cancer (NSCLC) and 1150 patients with small-cell lung cancer (SCLC) were included. Low and high platelet count were significantly associated with decreased overall survival (OS) in NSCLC patients (low: adjusted hazard ratio (HR)=1.75 (95% confidence interval [CI]: 1.49-2.06); high: adjusted HR=1.24 (95% CI: 1.16-1.33)). In SCLC patients, only low platelet count was significantly associated with decreased OS (adjusted HR = 2.71 [95% CI: 2.02-3.65]). C-statistics showed that the prognostic models were significantly improved by the addition of platelet count for both NSCLC and SCLC patients (P < .0001). ConclusionLow and high platelet count were adverse prognostic factors in NSCLC patients, while only low platelet count was a prognostic marker in SCLC patients.

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.

Synergistic polymorphic interactions of phase II metabolizing genes and their association toward lung cancer susceptibility in North Indians

ABSTRACT Lung cancer is a multifactorial carcinoma with diverse heterogeneity. Genetic variations in drug-metabolizing enzymes may lead to defective detoxification and clearance of carcinogenic compounds. The high-order gene-gene interaction has been carried out between different genotypes of Phase II detoxification genes (NQO1, SULT1A1, NAT2, and EPHX1). Our results depict the genetic combination of SULT1A1 R 213 H with NAT2 × 5B L 161 L, SULT1A1 R 213 H with NAT2 × 5C K 268 R, EPHX1 H 139 R and NAT2 × 5B L 161 L exhibit a protective effect towards lung cancer risk. Further, the triple combinations of NQO1 P 187 S, EPHX1 Y 113 H, and EPHX1 H 139 R; NQO1 P 187 S, EPHX1 Y 113 H, and NAT2 × 6 R 197 Q; NQO1 P 187 S, EPHX1 Y 113 H, and NAT2 × 7 G 286 E; SULT1A1 R 213 H, EPHX1 H 139 R, and NAT2 × 7 G 286 E suggested a two-fold increased risk of lung cancer for subjects. Genetic polymorphisms of phase II detoxifying genes (NAT2, NQO1, EPHX1, SULT1A1) are prognostic markers for lung cancer.

Integrative weighted molecular network construction from transcriptomics and genome wide association data to identify shared genetic biomarkers for COPD and lung cancer.

Chronic obstructive pulmonary disease (COPD) is a multifactorial progressive airflow obstruction in the lungs, accounting for high morbidity and mortality across the world. This study aims to identify potential COPD blood-based biomarkers by analyzing the dysregulated gene expression patterns in blood and lung tissues with the help of robust computational approaches. The microarray gene expression datasets from blood (136 COPD and 6 controls) and lung tissues (16 COPD and 19 controls) were analyzed to detect shared differentially expressed genes (DEGs). Then these DEGs were used to construct COPD protein network-clusters and functionally enrich them against gene ontology annotation terms. The hub genes in the COPD network clusters were then queried in GWAS catalog and in several cancer expression databases to explore their pathogenic roles in lung cancers. The comparison of blood and lung tissue datasets revealed 63 shared DEGs. Of these DEGs, 12 COPD hub gene-network clusters (SREK1, TMEM67, IRAK2, MECOM, ASB4, C1QTNF2, CDC42BPA, DPF3, DET1, CCDC74B, KHK, and DDX3Y) connected to dysregulations of protein degradation, inflammatory cytokine production, airway remodeling, and immune cell activity were prioritized with the help of protein interactome and functional enrichment analysis. Interestingly, IRAK2 and MECOM hub genes from these COPD network clusters are known for their involvement in different pulmonary diseases. Additional COPD hub genes like SREK1, TMEM67, CDC42BPA, DPF3, and ASB4 were identified as prognostic markers in lung cancer, which is reported in 1% of COPD patients. This study identified 12 gene network- clusters as potential blood based genetic biomarkers for COPD diagnosis and prognosis.

Emerging role of N6-methyladenosine RNA methylation in lung diseases.

In recent years, with the increase of air pollution, smoking, aging, and respiratory infection, the incidence rate and mortality of lung diseases are increasing annually, which has become a major hazard to human health. N6-methyladenosine (m6A) RNA methylation is the most abundant modifications in eukaryotes, and such modified RNA can be specifically recognized and combined by m6A recognition proteins and then mediate RNA splicing, maturation, enucleation, degradation, and translation. More and more studies have revealed that the m6A modification is involved in the pathogenesis and development of some diseases; however, the mechanisms of m6A in lung diseases are poorly understood. In this review, we summarize the latest progress in the biological function of m6A modifications in lung diseases and discuss the potential therapeutic and prognostic strategies. The dysregulation of global m6A levels and m6A regulators may affect the occurrence and development of asthma, chronic obstructive pulmonary disease, lung cancer, and other lung diseases through inflammation and immune function. In lung cancer, this modification has an important impact on malignant cell proliferation, migration, invasion, and drug resistance. In addition, abnormally changed m6A-modified proteins in lung cancer tissue samples and circulating tumor cells (CTCs) may be used as diagnostic and prognostic markers of lung cancer. Models composed of multiple m6A regulators can be used to evaluate the risk prediction or prognosis of asthma and pulmonary fibrosis. In general, the in-depth study of m6A modifications is a frontier direction in disease research. It provides novel insights for understanding of the molecular mechanisms underlying disease occurrence, development, and drug resistance, as well as for the development of effective novel therapeutics.

Tumor Microenvironment CD14+ Cells Correlate with Poor Overall Survival in Patients with Early-Stage Lung Adenocarcinoma.

Simple SummaryLung cancer is the leading cause of cancer-related deaths worldwide in part due to high rates of recurrence even with early-stage disease. This suggests that new biomarkers are needed to improve predictions for patient outcomes and better understand the underlying biology that drives poor outcomes. We believe the immune cells within the tumor microenvironment (TME) are a key differentiator between patients who are cured and patients who experience lung cancer relapse. In this study, we investigated the presence of CD14+ cells within the lung adenocarcinoma TME through immunohistochemistry and found that higher levels of CD14+ cells were correlated with shorter patient survival. In vitro studies revealed a bi-directional cross-talk between CD14+ cells and lung cancer that improved lung cancer cell recovery after chemotherapy. Our observations suggest that TME CD14+ infiltration is a prognostic marker in lung cancer and that further studies are needed to understand CD14+-cell-mediated mechanisms that influence patient outcomes.Patients with early-stage lung adenocarcinoma have a high risk of recurrent or metastatic disease despite undergoing curative intent therapy. We hypothesized that increased CD14+ cells within the tumor microenvironment (TME) could stratify patient outcomes. Immunohistochemistry for CD14 was performed on 189 specimens from patients with lung adenocarcinoma who underwent curative intent surgery. Outcomes and associations with clinical and pathologic variables were determined. In vitro studies utilized a coculture system to model the lung cancer TME containing CD14+ cells. Patients with high levels of TME CD14+ cells experienced a median overall survival of 5.5 years compared with 8.3 and 10.7 years for those with moderate or low CD14 levels, respectively (p < 0.001). Increased CD14+ cell tumor infiltration was associated with a higher stage at diagnosis and more positive lymph nodes at the time of surgery. This prognostic capacity remained even for patients with early-stage disease. Using an in vitro model system, we found that CD14+ cells reduced chemotherapy-induced cancer cell death. These data suggest that CD14+ cells are a biomarker for poor prognosis in early-stage lung adenocarcinoma and may promote tumor survival. CD14+ cell integration into the lung cancer TME can occur early in the disease and may be a promising new therapeutic avenue.

WD repeat domain 6 as a novelty prognostic biomarker correlates with immune infiltration in lung cancer: A preliminary study.

BackgroundWD repeat domain 6 (WDR6), a novel human WD‐repeat gene, encodes a member of the WD repeat protein family, and its tumorigenic effect has rarely been reported so far.MethodsOur study used Oncomine, TIMER2.0, GEPIA2, Kaplan–Meier plotter, PrognoScan, and TISIDB tools to analyze the differential expression between pan‐cancer, especially lung cancer, and corresponding normal tissue, and further explore the prognostic and immunological role of WDR6 expression.ResultsOur results showed WDR6 was lower expressed in lung squamous cell carcinoma than in normal tissue, but WDR6 expression was correlated obviously with clinical stage in Lung adenocarcinoma. The overall survival, first progression, postprogression survival, and Relapse‐free survival of lung cancer patients were longer in the WDR6 high‐expression group than in the low‐expression group. We found the expression of WDR6 significantly correlated with immune molecules, including immunomodulators, lymphocytes, and chemokines in lung cancer.ConclusionWDR6 can be used as a prognostic marker for lung cancer and is significantly associated with immune cell infiltration.

The Identification of NIFK’s RNA Binding Targets and Its Prognostic Values in Lung Cancer

BackgroundWe previously identified nucleolar protein interacting with the FHA domain of pKi‐67 (NIFK) as a poor prognostic marker in lung cancer. Furthermore, NIFK overexpression promotes cancer metastasis via decreasing casein kinase 1α (CK1α) expression, a suppressor of pro‐metastatic TCF4/β‐catenin signaling. We further observe the axis is induced by the downregulation of a novel transcription factor RUNX1. It is also known for NIFK’s biological function in regulating RNA metabolism via RNA recognition motif (RRM). However, a comprehensive analysis for identifying the RNA binding targets has not yet been reported. In this study, we aim to unravel the interactive mechanism and to characterize its potential clinical value in cancer patient cohort.MethodNIFK is pointed out to possess RNA binding function via RRM. RNA immunoprecipitation assay was performed using specific NIFK antibody in lung cancer PC13 and A549 cells after NIFK overexpression. RNA targets were analyzed by RT‐PCR and Next Generation Sequencing (NGS). In addition, expression levels were investigated by IHC staining and omics data mining. The association of the respective expression with patient survival outcome were explored in lung cancer cohorts.ResultsWe observe the increase in amount of RNA binding targets after NIFK overexpression respectively in PC13 and A549 cells as comparing with the control. Moreover, NIFK appears to bind with RUNX1 RNA but not CK1α suggesting it is the initial step of NIFK‐mediated TCF4/β‐catenin signaling regulation. NIFK also leads to RUNX1 RNA instability of which mechanism remains to be explored. RUNX1 level is observed to associate with good prognosis in lung cancer datasets (jacob‐00182‐CANDF and GSE13213). Furthermore, direct interactive RNA targets of NIFK are identified by RNA immunoprecipitation and RNA‐Seq, which indicate SYNE2 as one of targets with prognostic significance in lung cancer. Increased SYNE2 is detected upon NIFK overexpression, and the lung cancer patients stratified in high SYNE2 group appear to associate with inferior clinical outcomes.ConclusionWe first show the interactive mechanism of pro‐metastatic molecule NIFK in regulating TCF4/β‐catenin signaling and SYNE2, which might provide insights into therapeutic development for lung cancer patients.

Glycosylated Cathepsin V Serves as a Prognostic Marker in Lung Cancer.

Dysregulation of cysteine cathepsin protease activity is pivotal in tumorigenic transformation. However, the role of cathepsin protease in lung cancer remains unknown. Here, we analyzed GEO database and found that lung cancer presented high expression of cathepsin V (CTSV). We then performed immunohistochemistry assay in 73 paired lung cancer tissues and normal lung tissues and confirmed that CTSV is overexpressed in lung cancer and correlates with poor prognosis. The mass spectrometry experiment showed that the N-glycosylation locus of CTSV are N221 and N292, glycosylated CTSV (band 43 kDa) was particularly expressed in lung cancer samples and correlated with lymph node metastasis. Mechanistic studies showed that only glycosylated CTSV (43-kDa band) are secreted to extracellular matrix (ECM) and promoted the metastasis of lung cancer. Importantly, the Elisa detection in serum of 12 lung cancer patients and 12 healthy donors showed that the level of CTSV in serum distinguished lung cancer patients from healthy donors. Together, our findings reveal the clinical relevance of CTSV glycosylation and CTSV drives the metastasis of lung cancer, suggesting that the glycosylated CTSV in serum is a promising biomarker for lung cancer.

Expression and prognostic analyses of the significance of STEAP1 and STEAP2 in lung cancer

PurposeLung cancer is the leading cause of cancer-related mortality. STEAP1 and STEAP2 are overexpressed in various cancers. The purpose of this study was to evaluate the expression and prognostic value of STEAP1 and STEAP2 in patients with lung cancer.MethodsThe mRNA expression and protein expression of STEAP1 and STEAP2 and their prognostic characteristics were examined using Oncomine, GEPIA, and Kaplan-Meier (KM) plotters. The correlation analysis of STEAP1 and STEAP2 gene and protein levels was conducted using GeneMANIA and STRING. KEGG pathway analysis was used to explore the related signal pathways of STEAP 1 and STEAP2. Immunohistochemical methods were used to compare the expression of STEAP2 in normal lung and non-small cell lung cancer (NSCLC) tissues. Real-time quantitative polymerase chain reaction, western blotting, and immunocytochemistry were used to evaluate the expression of STEAP1 and STEAP2 in three lung cancer cell lines and normal lung epithelial cell lines.ResultsAnalysis of the Oncomine database and GEPIA showed that STEAP1 was upregulated and STEAP2 was downregulated in lung cancer tissue, and both expressions were related to the clinical stage of lung cancer. Immunohistochemical analysis showed that STEAP1 protein expression was significantly upregulated in lung cancer compared to that in adjacent tissues. The expression of STEAP1 was positively correlated with the migration and invasion abilities of lung cancer cells. Compared with paracancer tissues, the expression of STEAP2 protein in lung cancer was significantly downregulated and was correlated with the histological grade of squamous cell carcinoma, pathological classification of adenocarcinoma, tumor, lymph node, and metastasis clinical stage, and lymph node metastasis. The expression of STEAP2 was negatively correlated with the migration and invasion abilities of lung cancer cells. The KM curve showed that the downregulation of STEAP1 expression and upregulation of STEAP2 expression were related to a good lung cancer prognosis.ConclusionSTEAP1 and STEAP2 are expected to be potential diagnostic and prognostic markers for lung cancer, which may provide more accurate prognostic indicators for lung cancer.

Bioinformatics role of the WGCNA analysis and co-expression network identifies of prognostic marker in lung cancer

Lung cancer is the most talked about cancer in the world. It is also one of the cancers that currently has a high mortality rate. The aim of our research is to find more effective therapeutic targets and prognostic markers for human lung cancer. First, we download gene expression data from the GEO database. We performed weighted co-expression network analysis on the selected genes, we then constructed scale-free networks and topological overlap matrices, and performed correlation modular analysis with the cancer group. We screened the 200 genes with the highest correlation in the cyan module for functional enrichment analysis and protein interaction network construction, found that most of them focused on cell division, tumor necrosis factor-mediated signaling pathways, cellular redox homeostasis, reactive oxygen species biosynthesis, and other processes, and were related to the cell cycle, apoptosis, HIF-1 signaling pathway, p53 signaling pathway, NF-κB signaling pathway, and several cancer disease pathways are involved. Finally, we used the GEPIA website data to perform survival analysis on some of the genes with GS > 0.6 in the cyan module. CBX3, AHCY, MRPL12, TPGB, TUBG1, KIF11, LRRC59, MRPL17, TMEM106B, ZWINT, TRIP13, and HMMR was identified as an important prognostic factor for lung cancer patients. In summary, we identified 12 mRNAs associated with lung cancer prognosis. Our study contributes to a deeper understanding of the molecular mechanisms of lung cancer and provides new insights into drug use and prognosis.

The Emerging Roles of Long Noncoding RNAs as Hallmarks of Lung Cancer.

Noncoding ribonucleic acids (ncRNAs) are closely associated with tumor initiation, growth, and progress in lung cancer. Long ncRNAs (lncRNAs), as one of the three subclasses of ncRNAs, play important roles in chromatin modification, transcription, and post-transcriptional processing. Various lncRNAs have recently been reported to be dysfunctional or dysregulated in cancers and have pro- or anti-tumor potential. Importantly, as a new class of cancer biomarkers, studies have demonstrated the plausibility of using certain subsets of lncRNAs as promising diagnostic, therapeutic, or prognostic strategies to manage cancers. This review focuses on lncRNAs associated with hallmarks of lung cancer, especially those discovered in the last five years. The expression levels of these lncRNAs in tumor samples are discussed, alongside their mechanisms of action, drug resistance, and potential as diagnostic and prognostic markers for lung cancer.

Interferon-γ-Inducible Chemokines as Prognostic Markers for Lung Cancer.

Interferon (IFN)-γ-inducible chemokines in the CXCR3/ligand axis are involved in cell-mediated immunity and play a significant role in the progression of cancer. We enrolled patients with lung cancer (n = 144) and healthy volunteers as the controls (n = 140). Initial blood samples were collected and concentrations of IFN-γ and IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 were measured using enzyme-linked immunosorbent assay. Of patients with lung cancer, 125 had non-small cell lung cancer (NSCLC) and 19 had small cell lung cancer. The area under the curve (AUC) (95% CI) of CXCL9 was 0.83 (0.80–0.89) for differentiating lung cancer patients from controls. The levels of all the markers were significantly higher in NSCLC patients with stage IV than in those with stages I–III. A Kaplan-Meier survival analysis showed that NSCLC cancer patients with higher levels of all markers showed poorer survival than those with lower levels. In Cox multivariate analysis of patients with NSCLC, independent prognostic factors for overall survival were CXCL9 and CXCL11. CXCL9 was the only independent prognostic factor for cancer-specific survival. Serum IFN-γ-inducible chemokines may be useful as clinical markers of metastasis and prognosis in NSCLC, and CXCL9 levels showed the most significant results.

Downregulation of FPN1 acts as a prognostic biomarker associated with immune infiltration in lung cancer.

Lung cancer morbidity and mortality remain the leading causes of tumor-associated death worldwide. The discovery of early diagnostic and prognostic markers of lung cancer could significantly improve the survival rate and decrease the mortality rate. FPN1 is the only known mammalian iron exporter. However, the molecular and biological functions of FPN1 in lung cancer remain unclear. Here, FPN1 mRNA expression in lung cancer was estimated using the TCGA, Oncomine, TIMER, and UALCAN databases. The prognostic role of FPN1 was evaluated using Kaplan-Meier plotter and PrognoScan. Associations between FPN1 and immune infiltration in lung cancer were evaluated by the TIMER and CIBERSORT algorithms. FPN1 mRNA and protein expressions were significantly downregulated in lung cancer. Low FPN1 expression was strongly related to worse prognosis in patients with lung cancer. GO and KEGG analyses and GSEA suggested that FPN1 was remarkably related to iron homeostasis and immunity. Importantly, FPN1 was remarkably associated with the infiltrating abundance of multiple immune cells. Moreover, FPN1 displayed a strong correlation with various immune marker sets. We investigated the clinical application value of FPN1 and provided a basis for the sensitive diagnosis, prognostication and targeted therapy of lung cancer.