MiRNAs in Lung Adenocarcinoma: Role, Diagnosis, Prognosis, and Therapy
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ABSTRACT:
SUBMITTER: Song Y
PROVIDER: S-EPMC10487838 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:Ion channels are known to regulate cancer processes at all stages. The roles of ion channels in cancer pathology are extremely diverse. We systematically analyzed the expression patterns of ion channel genes in lung adenocarcinoma. First, we compared the expression of ion channel genes between normal and tumor tissues in patients with lung adenocarcinoma. Thirty-seven ion channel genes were identified as being differentially expressed between the two groups. Next, we investigated the prognostic power of ion channel genes in lung adenocarcinoma. We assigned a risk score to each lung adenocarcinoma patient based on the expression of the differentially expressed ion channel genes. We demonstrated that the risk score effectively predicted overall survival and recurrence-free survival in lung adenocarcinoma. We also found that the risk scores for ever-smokers were higher than those for never-smokers. Multivariate analysis indicated that the risk score was a significant prognostic factor for survival, which is independent of patient age, gender, stage, smoking history, Myc level, and EGFR/KRAS/ALK gene mutation status. Finally, we investigated the difference in ion channel gene expression between the two major subtypes of non-small cell lung cancer: adenocarcinoma and squamous-cell carcinoma. Thirty ion channel genes were identified as being differentially expressed between the two groups. We suggest that ion channel gene expression can be used to improve the subtype classification in non-small cell lung cancer at the molecular level. The findings in this study have been validated in several independent lung cancer cohorts.
| S-EPMC3900557 | biostudies-literature
Project description:BackgroundLong noncoding RNAs have been demonstrated to play important roles in different kinds of human malignancy. The purpose of this study was to evaluate the diagnostic and prognostic value of long intergenic non-protein coding RNA 1232 (LINC01232) in patients with pancreatic adenocarcinoma (PAAD) and further explore the clinical significance of the potential miRNAs that might be sponged by LINC01232.MethodsThe potential target miRNAs that might be sponged by LINC01232 were analyzed using bioinformatics analysis. The Real-Time quantitative PCR was adopted to measure the relative expression of LINC01232 and target miRNAs in PAAD serum and tissue samples. The diagnostic and prognostic value of LINC01232 was evaluated using the receiver operating characteristic analysis and Kaplan-Meier survival analysis, respectively.ResultsLINC01232 expression was upregulated in PAAD serum and tissues and associated with patients' TNM stage. Serum LINC01232 expression had diagnostic value, and the high levels of LINC01232 could predict unfavorable prognosis in PAAD patients. miR-204-5p, miR-370-5p and miR-654-3p were proposed as 3 targets of LINC01232 in PAAD, and their decreased expression levels in PAAD patients showed certain clinical significance in diagnosis and prognosis.ConclusionThe data of this study revealed that LINC01232 expression is upregulated in PAAD serum and tissue samples with considerable diagnostic and prognostic significance. In addition, miR-204-5p, miR-370-5p and miR-654-3p may be sponged by LINC01232 in PAAD, which also show potencies in PAAD diagnosis and prognosis.
| S-EPMC7871353 | biostudies-literature
Project description:BackgroundConsidering the absence of apparent symptoms at the early stage, most patients with lung adenocarcinoma (LUAD) present at an advanced stage, leading to a dismal 5-year survival rate of <20%. Thus, finding perspective non-invasive biomarkers for early LUAD is very essential.MethodsWe developed a fucose-captured strategy based on lentil lectin-magnetic beads to isolate fucosylated exosomes from serum. Then, a prospective study was conducted to define the diagnostic value of serum exosomal miRNAs for early LUAD. A total of 310 participants were enrolled, including 146 LUAD, 98 benign pulmonary nodules (BPNs), and 66 healthy controls (HCs). Firstly, exosome miRNAs in the discovery cohort (n = 24) were profiled by small RNA sequencing. Secondly, 12 differentially expressed miRNAs (DEmiRs) were selected for further screening in a screening cohort (n = 64) by qRT-PCR. Finally, four candidate miRNAs were selected for further validation in a validating cohort (n = 222).ResultsThis study demonstrated the feasibility of a fucose-captured strategy for the isolation of fucosylated exosomes from serum, evidenced with exosomal characteristics identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting, as well as rapid and convenient operation of <10 min. Furthermore, a miRNA panel for early LUAD composed of miR4732-5p, miR451a, miR486-5p, and miR139-3p was defined with an AUC of 0.8554 at 91.07% sensitivity and 66.36% specificity.ConclusionsThe fucose-captured strategy provides a reliable, as well as rapid and convenient, approach for the isolation of tumor-derived exosomes from serum. A four-fucosylated exosomal miRNA panel presents good performance for early LUAD diagnosis.
| S-EPMC9414872 | biostudies-literature
Project description:MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.
| S-EPMC7072450 | biostudies-literature
Project description:Lung cancer is often diagnosed at an advanced stage and has a poor prognosis. Conventional treatments are not effective for metastatic lung cancer therapy. Although some of molecular targets have been identified with favorable response, those targets cannot be exploited due to the lack of suitable drug carriers. Lung cancer cell-derived exosomes (LCCDEs) receive recent interest in its role in carcinogenesis, diagnosis, therapy, and prognosis of lung cancer due to its biological functions and natural ability to carry donor cell biomolecules. LCCDEs can promote cell proliferation and metastasis, affect angiogenesis, modulate antitumor immune responses during lung cancer carcinogenesis, regulate drug resistance in lung cancer therapy, and be now considered an important component in liquid biopsy assessments for detecting lung cancer. Therapeutic deliverable exosomes are emerging as promising drug delivery agents specifically to tumor high precision medicine because of their natural intercellular communication role, excellent biocompatibility, low immunogenicity, low toxicity, long blood circulation ability, biodegradable characteristics, and their ability to cross various biological barriers. Several studies are currently underway to develop novel diagnostic and prognostic modalities using LCCDEs, and to develop methods of exploiting exosomes for use as efficient drug delivery vehicles. Current status of lung cancer and extensive applicability of LCCDEs are illustrated in this review. The promising data and technologies indicate that the approach on LCCDEs implies the potential application of LCCDEs to clinical management of lung cancer patients.
| S-EPMC7839206 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD), the most common histological type of non-small cell lung cancer, is one of the most malignant and deadly diseases. Current treatments for advanced LUAD patients are far from ideal and require further improvements. Here, we utilized a systematic integrative analysis of LUAD microRNA sequencing (miRNA-seq) and RNA-seq data from The Cancer Genome Atlas (TCGA) to identify clinically relevant tumor suppressor miRNAs. Three miRNA candidates (miR-195-5p, miR-101-3p, and miR-338-5p) were identified based on their differential expressions, survival significance levels, correlations with targets, and an additive effect on survival among them. We further evaluated mimics of the three miRNAs to determine their therapeutic potential in inhibiting cancer progression. The results showed not only that each of the miRNA mimics alone but also the three miRNA mimics in combination were efficient at inhibiting tumor growth and progression with equal final concentrations, meaning that the three miRNA mimics in combination were more effective than the single miRNA mimics. Moreover, the combined miRNA mimics provided significant therapeutic effects in terms of reduced tumor volume and metastasis nodules in lung tumor animal models. Hence, our findings show the potential of using the three miRNAs in combination to treat LUAD patients with poor survival outcomes.
| S-EPMC8181588 | biostudies-literature
Project description:Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), circulating freely in the blood stream or entrapped in extracellular vesicles (EVs), have been shown to have a potential diagnostic, prognostic or predictive power. In this review, recent findings are summarized, both at a preclinical and clinical level, related to miRNA applicability in the context of breast cancer. Different aspects, including clinical and technical challenges, are discussed, describing the potentialities of miRNA use in breast cancer. Even though more methodological standardized studies conducted in larger and selected patient cohorts are needed to support the effective clinical utility of miRNA as biomarkers, they could represent novel and accessible tools to be transferred into clinical practice.
| S-EPMC9101355 | biostudies-literature
Project description:Background: Because lung cancer is the main cause of cancer deaths and lung adenocarcinoma (LUAD) accounts for more than 40% of all lung malignancies, it is essential to develop clinically useful biomarkers for the disease. The aim of this investigation is to assess the potential application of tubulin alpha-1b (TUBA1B) as a biomarker for diagnosing and monitoring the outcome of LUAD. Methods: The clinical data of the LUAD patients was retrospectively analyzed. Immunohistochemistry (IHC) analysis of a tissue microarray containing 90 LUAD cases was implemented to examine the expression of TUBA1B. The protein and mRNA levels of TUBA1B in serum were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) analysis respectively. UALCAN was employed to confirm the expression levels and survival probability of TUBA1B in LUAD patients. Results: Compared to adjacent non-cancerous tissues in the microarray, the expression of TUBA1B in LUAD tissues was much higher. The expression of TUBA1B in LUAD was statistically correlated with lymph node status (P = .031). Moreover, patients with higher TUBA1B expression had shorter overall survival (P < .0001). Furthermore, cox multi-factor analysis also suggested that TUBA1B may be an independent predictor for LUAD prognosis (P = .030). The results of TCGA data analysis by UALCAN were consistent with the microarray results, except for that TUBA1B was also significantly correlated with clinical tumor stages. Protein levels of TUBA1B in serum were obviously elevated in LUAD patients than control (P < .0001), and the area under the ROC curve was 0.99. TUBA1B also showed better sensitivity of 92.9% for LUAD than common clinical biomarkers. Conclusion: TUBA1B may be a non-invasive prognostic and diagnostic biomarker for LUAD patients.
| S-EPMC10369087 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. At present, most patients with LUAD are diagnosed at an advanced stage, and the prognosis of advanced LUAD is poor. Hence, we aimed to identify novel biomarkers for the diagnosis and treatment of early stage LUAD and to explore their predictive value.MethodsThe microarray datasets GSE63459, GSE27262, and GSE33532 were searched, and the differentially expressed genes (DEGs) were obtained using GEO2R. The DEGs were subjected to gene ontology (GO) and pathway enrichment analyses using METASCAPE. A protein-protein interaction (PPI) network was plotted with STRING and visualized by Cytoscape. Module analysis of the PPI network was performed using MCODE. Overall survival (OS) analysis and analysis of the mRNA expression levels of genes identified by MCODE were performed with UALCAN. Western blot analysis of hub genes in LUAD patients, MTS assays, and clonogenic assays were performed to test the effects of the hub genes on cell proliferation in vitro.ResultsA total of 341 DEGs were obtained, which were mainly enriched in terms related to blood vessel development, growth factor binding, and extracellular matrix organization. A PPI network consisting of 300 nodes and 1140 edges was constructed, and a significant module including 15 genes was identified. Elevated expression of ASPM, CCNB2, CDCA5, PRC1, KIAA0101, and UBE2T was associated with poor OS in LUAD patients. In the protein level, the hub gene was overexpressed in LUAD patients. In vitro experiments showed that knockdown of the hub genes in the LUAD cell lines could promote cell proliferation.ConclusionsDEGs are potential biomarkers for early stage lung adenocarcinoma and could have utility for the diagnosis and predicting treatment efficacy.
| S-EPMC8085413 | biostudies-literature
Project description:Previous studies have reported that the aberrant expression of circulating microRNAs (miRNAs/miRs) can be used as diagnostic and prognostic markers in non-small cell lung cancer (NSCLC). The present study aimed to assess the diagnostic and prognostic predictive values of four plasma miRNAs for NSCLC. A total of 12 candidate miRNAs were selected that have previously been reported to be aberrantly expressed in NSCLC, and their plasma levels in the training set were detected via reverse transcription-quantitative PCR analysis. The screened out miRNAs were further validated in the testing set. The area under the curve (AUC) of the receiver operating characteristic curve was constructed to evaluate diagnostic performance. Kaplan-Meier survival analysis was performed to assess the association between the plasma miRNA levels and disease-free survival (DFS) time. The results demonstrated that 4/12 plasma miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) were highly expressed in patients with NSCLC compared with their expression levels in patients with benign lung disease (BLD) and healthy controls in the training and testing sets, respectively. The AUC values of the four-miRNA panel were 0.96 and 0.93 in the training and testing sets, respectively, for distinguishing patients with NSCLC from healthy controls, which were similar to the AUC values for distinguishing patients with NSCLC from patients with BLD (0.96 and 0.94). The AUC values of the four-miRNA panel in patients with stage I NSCLC were comparable to that of patients with stage II-III NSCLC (0.942 and 0.965). Patients with high plasma levels of miR-210 and miR-150 had worse DFS than those with low plasma levels of these miRNAs. In addition, patients whose plasma levels of the four miRNAs decreased by >50% after surgery exhibited a good DFS. Taken together, the results of the present study suggest that these four miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) act as useful biomarkers for early diagnosis and prognosis of NSCLC.
| S-EPMC8477070 | biostudies-literature