Comprehensive Analysis of Alteration Landscape and Its Clinical Significance of Mitochondrial Energy Metabolism Pathway-Related Genes in Lung Cancers

Background. Mitochondria are the energy factories of cells. The abnormality of mitochondrial energy metabolism pathways is closely related to the occurrence and development of lung cancer. The abnormal genes in mitochondrial energy metabolism pathways might be the novel targets and biomarkers to diagnose and treat lung cancers. Method. Genes in major mitochondrial energy metabolism pathways were obtained from the KEGG database. The transcriptomic, mutation, and clinical data of lung cancers were obtained from The Cancer Genome Atlas (TCGA) database. Genes and clinical biomarkers were mined that affected lung cancer survival. Gene enrichment analysis was performed with ClusterProfiler and the gene set enrichment analysis (GSEA). STRING database and Cytoscape were used for protein-protein interaction (PPI) analysis. The diagnostic biomarker pattern of lung cancer was optimized, and its accuracy was verified with 10-fold cross-validation. The four genes screened by logistic regression model were verified by western blot in 5 pairs of lung cancer specimens collected in hospital. Results. In total, 188 mitochondrial energy metabolism pathway-related genes (MMRGs) were included in this study. GSEA analysis found that MMRGs in the lung cancer group were mainly enriched in the metabolic pathway of oxidative phosphorylation and electron respiratory transport chain compared to the control group. Age did not affect the mutation frequency of MMRGs. Comparative analysis of these 188 MMRGs identified 43 differentially expressed MMRGs (24 upregulated and 19 downregulated) in the lung cancer group compared to the control group. The survival analysis of these 43 differentially expressed MMRGs found that the survival time was better in the low-expressed GAPDHS group than that in the high-expressed GAPDHS group of lung cancers. The advanced age, high expression of GAPDHS, low expressions of ACSBG1 and CYP4A11, and ACOX3 mutation were biomarkers of poor prognosis in lung cancers. PPI analysis showed that proteins such as GAPDH and GAPDHS interacted with many proteins in mitochondrial metabolic pathways. A four-MMRG-signature model ( y = 0.0069 ∗ ACADL − 0.001 ∗ ALDH 18 A 1 − 0.0405 ∗ CPT 1 B + 0.0008 ∗ PPARG − 1.625 ) was established to diagnose lung cancer with the accuracy up to 98.74%, AUC value up to 0.992, and a missed diagnosis rate of only 0.6%. Western blotting showed that ALDH18A1 and CPT1B proteins were significantly overexpressed in the lung cancer group ( p < 0.05 ), and ACADL and PPARG proteins were slightly underexpressed in the lung cancer group ( p < 0.05 ), which were consistent with the results of their corresponding mRNA expressions. Conclusion. Mitochondrial energy metabolism pathway alterations are the important hallmarks of lung cancer. Age did not increase the risk of MMRG mutation. High expression of GAPDHS, low expression of ACSBG1, low expression of CYP4A11, mutated ACOX3, and old age predict a poor prognosis of lung cancer. Four differentially expressed MMRGs (ACADL, ALDH18A1, CPT1B, and PPARG) established a logistic regression model, which could effectively diagnose lung cancer. At the protein level, ALDH18A1 and CPT1B were significantly upregulated, and ACADL and PPARG were slightly underexpressed, in the lung cancer group compared to the control group, which were consistent with the results of their corresponding mRNA expressions.

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Target identification of hepatic fibrosis using Pien Tze Huang based on mRNA and lncRNA

Scientific Reports ◽

10.1038/s41598-021-96459-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jinhang Zhu ◽

Di Zhang ◽

Ting Wang ◽

Zhiliang Chen ◽

Luan Chen ◽

...

Keyword(s):

Liver Injury ◽

Hepatic Fibrosis ◽

Drug Targets ◽

Enrichment Analysis ◽

Inflammatory Cells ◽

Differentially Expressed ◽

Control Group ◽

Traditional Chinese Herbal Medicine ◽

Hepatic Diseases ◽

Pien Tze Huang

AbstractHepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury. Pien Tze Huang (PZH), a traditional Chinese herbal medicine, has been widely used to treat various hepatic diseases in Asia. We used a CCl4-induced mouse model to establish a PZH group of hepatic fibrosis mice treated with PZH and a control group of hepatic fibrosis mice without any treatment. We performed RNA-seq and mass spectrometry sequencing to investigate the mechanism of the PZH response in hepatic fibrosis and identified multiple differentially expressed transcripts (DETs) and proteins (DEPs) that may be drug targets of PZH. Liver functional indices, including serum albumin (ALB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in the PZH treatment group (P < 0.05) in the eighth week. Hematoxylin–eosin (HE), Masson and Sirius red staining demonstrated that PZH significantly inhibited infiltration of inflammatory cells and collagen deposition. A total of 928 transcripts and 138 proteins were differentially expressed in PZH-treated mice compared to the control group. Gene Ontology (GO) enrichment analysis suggested that PZH may alleviate liver injury and fibrosis by enhancing the immune process. Taken together, our results revealed that multiple DETs and DEPs may serve as drug targets of PZH in hepatic fibrosis patient in future clinical practice.

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Mobile Low-Dose Computed Tomographic (LDCT) Scanning combined with Remote Reading: a feasible approach to lung cancer screening among rural population

10.21203/rs.3.rs-430566/v1 ◽

2021 ◽

Author(s):

Bojiang Chen ◽

Jun Shao ◽

Jinghong Xian ◽

Pengwei Ren ◽

Wenxin Luo ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Screening ◽

Rural Areas ◽

Pulmonary Nodules ◽

Lung Cancer Screening ◽

Western China ◽

Control Group ◽

Local Hospital ◽

Lung Cancers ◽

Computed Tomographic

Abstract BackgroundLow-dose computed tomographic (LDCT) screening has been proven to be powerful in detecting lung cancers in early stage. However, it’s hard to carry out in less-developed regions in lacking of facilities and professionals. The feasibility and efficacy of mobile LDCT scanning combined with remote reading by experienced radiologists from superior hospital for lung cancer screening in deprived areas was explored in this study.MethodsA prospective cohort was conducted in rural areas of western China. Residents over 40 years old were invited for lung cancer screening by mobile LDCT scanning combined with remote image reading or local hospital-based LDCT screening. Rates of positive pulmonary nodules and detected lung cancers in the baseline were compared between the two groups.ResultsAmong 8073 candidates with preliminary response, 7251 eligibilities were assigned to the mobile LDCT with remote reading (n = 4527) and local hospital-based LDCT screening (n = 2724) for lung cancer. Basic characteristics of the subjects were almost similar in the two cohorts except that the mean age of participants in mobile group was relatively older than control (61.18 vs. 59.84 years old, P < 0.001). 1778 participants with mobile LDCT scans with remote reading (39.3%) revealed 2570 pulmonary nodules or mass, and 352 subjects in the control group (13.0%) were detected 472 ones (P < 0.001). Proportions of nodules less than 8 mm or subsolid were both more frequent in the mobile LDCT group (83.3% vs. 76.1%, 32.9% vs. 29.8%, respectively; both P < 0.05). In the baseline screening, 26 cases of lung cancer were identified in the mobile LDCT scanning with remote reading cohort, with a lung cancer detection rate of 0.57% (26/4527), which was significantly higher than control (4/2724 = 0.15%, P = 0.006). Moreover, 80.8% (21/26) of lung cancer patients detected by mobile CT with remote reading were in stage I, remarkedly higher than that of 25.0% in control (1/4, P = 0.020).ConclusionMobile LDCT combined with remote reading is probably a potential mode for lung cancer screening in rural areas.Trial registrationNo. of registration trial was ChiCTR-DDD-15007586 (http://www.chictr.org).

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MicroRNA expression profiling involved in Borax-induced anti-tumor effect using gene-chip analysis

10.21203/rs.2.20621/v1 ◽

2020 ◽

Author(s):

Lun Wu ◽

Ying Wei ◽

Wen-Bo Zhou ◽

Jiao Zhou ◽

Li-Hua Yang ◽

...

Keyword(s):

Signaling Pathway ◽

Hepg2 Cells ◽

Enrichment Analysis ◽

Gene Chip ◽

Differentially Expressed ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Ras Signaling ◽

Therapeutic Benefits ◽

Differentially Expressed Mirnas

Abstract Background Borax, a boron compound, which is becoming widely recognized for its biological effects, including antioxidant activity, cytotoxicity, and potential therapeutic benefits. However, the specific molecular mechanisms underlying borax-induced anti-tumor effect still remain to be to further elucidated. MicroRNAs (miRNAs) may play key roles in cellular processes including tumor progression, cell apoptosis and cytotoxicity. Thus, this study aimed to investigate, whether miRNAs were involved in the borax-mediated anti-tumor effect using miRNA profiling of a human liver cancer cell line (HepG2) using gene-chip analysis.Methods Total RNA was extracted and purified from HepG2 cells that were treated with 4 mM borax for either 2 or 24 h. The samples underwent microarray analysis using an Agilent Human miRNA Array. Differentially expressed miRNAs were analysed by volcano plot and heatmap, and were validated using real-time fluorescent quantitative PCR (qPCR).ResultsAmong this, 2- or 24-h exposure to borax significantly altered the expression level of miRNAs in HepG2 cells, 4 or 14 were upregulated and 3 were downregulated compared with the control group, respectively (≥2-fold; P<0.05). GO enrichment analysis and KEGG pathway enrichment analysis revealed that target genes of differentially expressed miRNAs in HepG2 cells predominantly participated in MAPK signaling pathway, TGF-beta signaling pathway, NF-kappa B signaling pathway, etc; in 2-h borax treatment group, while Ras signaling pathway, FoxO signaling pathway, Cellular senescence, etc; involved in 24-h treatment group.Conclusions Result indicates that borax-induced anti-tumor effect may be associated with alterations in miRNAs.

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Proteomic analysis of tears and serum for dry eye disease using ovariectomized cynomolgus monkey

10.21203/rs.2.21889/v1 ◽

2020 ◽

Author(s):

xiaolong yang ◽

Yue Xu ◽

Yun Wang ◽

Chang Li ◽

Xiaofeng Zhang

Keyword(s):

Gene Ontology ◽

Growth Factor ◽

Dry Eye ◽

Cynomolgus Monkey ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Control Group ◽

Differentially Expressed Proteins ◽

Dry Eyes ◽

Experimental Group

Abstract Background Ovariectomized cynomolgus monkey 30 months after surgery was selected as the research object to identify protein changes in tears and serum to provide a reference for the diagnosis and pathogenesis of dry eye in menopausal women. Methods Six cynomolgus monkey were randomly divided into an experimental group and a control group (3 in each group). The experimental group underwent bilateral ovariectomy, while the control group underwent sham surgery with their ovaries reserved. Proteomic analysis was performed by LC-MS/MS on tears and serum collected from two groups. Differentially expressed proteins were identified and were performed cluster analysis, which included gene ontology, the Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction. Results 33 differentially expressed proteins have been identified in tears and17 differentially expressed proteins have been identified in serum. Kyoto Encyclopedia of Genes and Genomes enrichment analysis in tears has discovered Glucagon signaling pathway and neurotrophin signaling pathway may play an important role in the pathogenesis of dry eye. Gene ontology enrichment analysis in serum has discovered insulin-like growth factor binding and growth factor binding in molecular function probably make effort in pathogenesis of dry eye. KEGG analysis in serum has discovered salivary secretion may be the key pathway in pathogenesis of dry eye. Conclusions Protein G7PCH4, Q2PG17 and G7PT55 in tears may be the key protein in pathogenesis of dry eyes. Protein G7P1T1, G7PUN9 and G8F302 in serum may play an important role in pathogenesis of dry eyes.

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Genomic profiling of cancerous patients identifies FPR2 as an alternative immunotherapeutic target in glioblastoma multiforme

10.1101/2020.12.26.424414 ◽

2020 ◽

Author(s):

Yuqing Yang ◽

Ting Sun ◽

Chuchen Qiu ◽

Dongjing Chen ◽

You Wu

Keyword(s):

Glioblastoma Multiforme ◽

Tumor Progression ◽

Differentially Expressed Genes ◽

Primary Tumor ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Control Group ◽

Western Blots ◽

Potential Biomarker

ABSTRACTBackgroundGlioblastoma multiforme (GBM) is a type of high-grade brain tumor known for its proliferative, invasive property, and low survival rate. Recently, with the advancement in therapeutics for tumors such as targeted therapy, individual cancer-specific biomarkers could be recognized as targets for curative purposes. This study identified six differentially expressed genes that have shown significant implications in clinical field, including FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3. FPR2 was of the same protein family with FPR1, and the latter has been repeatedly reported to promote motility and invasiveness of multiple tumor forms.MethodsThe gene expression profiling of 40 GBM samples and five normal samples from the TCGA database were comprehensively analyzed. The differentially expressed genes (DEGs) were identified using R package and screened by enrichment analysis and examination of protein–protein interaction networks, in order to further explore the functions of DEGs with the highest association with clinical traits and to find hub genes. A qRT-PCR and Western blots were conducted to verify the results of this study.ResultsOur investigation showed that FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly up-regulated in GBM primary tumor compared to the control group. Functional enrichment analysis of the DEGs demonstrated that biological functions related to immune systems, cell division and cell cycle were significantly increased, which were closely related to tumor progression and development. Downstream construction of PPI network analysis indicated that FPR2 was a hub gene involved in high level of interaction with CR3 and VEGFA, which played a key role in inflammatory pathways and cellular dysfunction.ConclusionFPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly over-expressed in primary tumor samples of GBM patients and were involved in cellular functions and pathways contributing to tumor progression. Out of these six pivotal genes, we intensively focused on FPR2, and our analysis and experimental data both suggested its efficacy as a potential biomarker, serving as an alternative immunotherapeutic target for glioblastoma multiforme.

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Expression Signatures of Long Noncoding RNAs in Left Ventricular Noncompaction

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.763858 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qingshan Tian ◽

Hanxiao Niu ◽

Dingyang Liu ◽

Na Ta ◽

Qing Yang ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Noncoding Rnas ◽

Enrichment Analysis ◽

Left Ventricular ◽

Long Noncoding Rnas ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Control Group ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction

Long noncoding RNAs have gained widespread attention in recent years for their crucial role in biological regulation. They have been implicated in a range of developmental processes and diseases including cancer, cardiovascular, and neuronal diseases. However, the role of long noncoding RNAs (lncRNAs) in left ventricular noncompaction (LVNC) has not been explored. In this study, we investigated the expression levels of lncRNAs in the blood of LVNC patients and healthy subjects to identify differentially expressed lncRNA that develop LVNC specific biomarkers and targets for developing therapies using biological pathways. We used Agilent Human lncRNA array that contains both updated lncRNAs and mRNAs probes. We identified 1,568 upregulated and 1,141 downregulated (log fold-change > 2.0) lncRNAs that are differentially expressed between LVNC and the control group. Among them, RP11-1100L3.7 and XLOC_002730 are the most upregulated and downregulated lncRNAs. Using quantitative real-time reverse transcription polymerase chain reaction (RT-QPCR), we confirmed the differential expression of three top upregulated and downregulated lncRNAs along with two other randomly picked lncRNAs. Gene Ontology (GO) and KEGG pathways analysis with these differentially expressed lncRNAs provide insight into the cellular pathway leading to LVNC pathogenesis. We also identified 1,066 upregulated and 1,017 downregulated mRNAs. Gene set enrichment analysis (GSEA) showed that G2M, Estrogen, and inflammatory pathways are enriched in differentially expressed genes (DEG). We also identified miRNA targets for these differentially expressed genes. In this study, we first report the use of LncRNA microarray to understand the pathogenesis of LVNC and to identify several lncRNA and genes and their targets as potential biomarkers.

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Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Blood to Distinguish Lung Cancer Patients from Healthy Subjects

Disease Markers ◽

10.1155/2020/8844698 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Xuming Zhu ◽

Huizhu Song ◽

Yan Chen ◽

Feifei Han ◽

Qiong Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Healthy Subjects ◽

Control Group ◽

Healthy Individuals ◽

Platelet To Lymphocyte Ratio ◽

Lung Cancer Patients ◽

Lymphocyte Ratio ◽

Cancer Group ◽

Level Group

Objective. Inflammation-driven markers play a crucial role in tumorigenesis and tumor progression. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in blood are systemic inflammatory response markers. Some reports have showed that NLR and PLR are related to a poor prognosis in patients with lung cancer. However, little studies have reported whether NLR and PLR can be diagnostic markers for lung cancer. The aim of the current study is to investigate the roles of NLR and PLR in diagnosing lung cancer. Methods. This study analyzed data from lung cancer patients and healthy individuals in Wuxi People’s Hospital Affiliated with Nanjing Medical University. The Mann–Whitney U test was performed to compare differences between the lung cancer group and the control group. Based on white blood cell (WBC) counts, both lung cancer patients and healthy individuals were divided into the low-level group, moderate-level group, and high-level group. The Kruskal-Wallis test was applied to compare differences of NLR and PLR among those groups with different WBC counts. Spearman correlation analysis was used to assess correlations. Receiver operating characteristic (ROC) curves were performed to determine diagnostic accuracy. Results. 210 patients diagnosed with lung cancer and 261 healthy subjects were enrolled in this study. Levels of NLR and PLR increased in the lung cancer group compared with the control group ( P < 0.001 ). For the lung cancer group, NLR levels could rise with the increasing of WBC levels ( P < 0.001 ) while PLR levels had no significant variation with the increasing of WBC levels ( P = 0.206 ). For the control group, NLR levels could rise with the increasing of WBC levels ( P < 0.001 ) while PLR levels would decline with the increasing of WBC levels ( P < 0.001 ). In the lung cancer group, both NLR and PLR had no significant correlations with aspartate transaminase, urea, and glucose. The area under the curve (AUC) with 95% confidence interval (95% CI) of NLR and PLR to distinguish lung cancer patients from healthy subjects was, respectively, 0.684 (0.634-0.735) and 0.623 (0.571-0.674). When NLR and PLR were combined, AUC (95% CI) increased to 0.691 (0.642-0.740). Conclusions. NLR and PLR alone have moderate ability to distinguish lung cancer patients from healthy subjects. Furthermore, combination forms of NLR and PLR can improve diagnostic ability.

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Meta-analysis of Correlation between Peripheral Serum MIC-1 level and Lung Cancer

Tobacco Regulatory Science ◽

10.18001/trs.7.5.1.210 ◽

2021 ◽

Vol 7 (5) ◽

pp. 4324-4331

Author(s):

Lei Dai ◽

Yongyong Wang ◽

Mingwu Chen

Keyword(s):

Lung Cancer ◽

Roc Curve ◽

Clinical Characteristics ◽

Meta Analysis ◽

Search Time ◽

Healthy People ◽

Control Group ◽

High Morbidity ◽

Cancer Group ◽

The Difference

Lung cancer (LC) is a common malignant tumor with high morbidity and mortality. The development of new molecular markers and the early diagnosis of LC and the exploration of emerging targeted therapies are of great significance. Therefore, this study systematically evaluates the correlation between peripheral serum MIC-1 levels and LC. Search PubMed, Web of Science, Medline and other databases, the search time is from the establishment of the database to July 2021. The LC group included LC patients, the Non-cancer group included patients with benign lung diseases (BLD), and the control group included healthy people. The serum MIC-1 levels of LC group and control group, LC group and Non-cancer group were compared respectively, and the correlation between serum MIC-1 and clinical characteristics of LC patients was evaluated and analyzed, and the ROC curve of MIC-1 in prediction of LC. Finally, 5 articles were included, including 1179 patients with LC, 109 patients with BLD, and 1020 healthy people. Meta-analysis results: the level of MIC-1 in LC group was overtop that in healthy group, and the difference was obvious [SMD=1.97, 95%CI (1.35, 2.59), PC0.00001]. The level of MIC-1 in LC group was overtop that in Non-cancer group, and the difference was obvious [SMD=382.97,95%CI (313.74, 452.19), PC0.00001]. The descriptive evaluation analyzes the correlation between MIC-1 and the clinical characteristics of LC group, and the results show that MIC-1 has a certain correlation with the stage of LC group. The AUC of serum MIC-1 in the identification of LC group and the control group was greater than 0.5. The AUC value of MIC-1 in the diagnosis of LC was 0.851-0.906, and the best sensitivity range was 63.50%-99.00%. The best specificity is in the range of 70.4%-95.80%. The Meta-analysis indicated that the serum MIC-1 level in LC group is overtop that in BLD and healthy people, and has a obvious correlation with LC stage staging; and the ROC curve shows that it has important significance in the diagnosis and prognosis of LC.

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Comprehensive analysis of coding and non-coding RNA transcriptomes related to hypoxic adaptation in Tibetan chickens

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-021-00582-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ying Zhang ◽

Woyu Su ◽

Bo Zhang ◽

Yao Ling ◽

Woo Kyun Kim ◽

...

Keyword(s):

Energy Metabolism ◽

High Altitude ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Tibet Plateau ◽

Hypoxic Adaptation ◽

Native Breed ◽

Non Coding Rnas

Abstract Background Tibetan chickens, a unique native breed in the Qinghai-Tibet Plateau of China, possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment. Increasing evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play roles in the hypoxic adaptation of high-altitude animals, although their exact involvement remains unclear. Results This study aimed to elucidate the global landscape of mRNAs, lncRNAs, and miRNAs using transcriptome sequencing to construct a regulatory network of competing endogenous RNAs (ceRNAs) and thus provide insights into the hypoxic adaptation of Tibetan chicken embryos. In total, 354 differentially expressed genes (DE genes), 389 differentially expressed lncRNAs (DE lncRNAs), and 73 differentially expressed miRNAs (DE miRNAs) were identified between Tibetan chickens (TC) and control Chahua chickens (CH). GO and KEGG enrichment analysis revealed that several important DE miRNAs and their target DE lncRNAs and DE genes are involved in angiogenesis (including blood vessel development and blood circulation) and energy metabolism (including glucose, carbohydrate, and lipid metabolism). The ceRNA network was then constructed with the predicted DE gene-DE miRNA-DE lncRNA interactions, which further revealed the regulatory roles of these differentially expressed RNAs during hypoxic adaptation of Tibetan chickens. Conclusions Analysis of transcriptomic data revealed several key candidate ceRNAs that may play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and energy metabolism. These results provide insights into the molecular mechanisms of hypoxic adaptation regulatory networks from the perspective of coding and non-coding RNAs.

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Potential for the blood- biomarker cell free UPK2 RNA to detect recurrence during monitoring after surgical resection of adenocarcinoma of the lung

10.21203/rs.3.rs-25690/v2 ◽

2020 ◽

Author(s):

Ji Zhu ◽

Qijue Lu ◽

Bin Li ◽

Huafei Li ◽

Cong Wu ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Malignant Tumors ◽

Early Stage ◽

Enrichment Analysis ◽

Postoperative Recurrence ◽

Expression Level ◽

Central Position ◽

Lung Cancers ◽

Gene Modules

Abstract Background: Lung cancer is one of the most common malignant tumors in the world. Non-small-cell lung cancer (NSCLC) accounting for top of all diagnosed lung cancers. Lung adenocarcinoma(LUAD) is the most common subtype in NSCLC. This study attempts to identify and validate biomarkers that can be used to monitor recurrence after LUAD surgery. Methods: In this research, we downloaded lung adenocarcinoma data from the TCGA database and selected postoperative recurrence samples, and then performed WGCNA analysis to find key co-expression gene modules. Enrichment analysis of key gene modules was also performed using the DAVID database. Finally, we performed a survival analysis of the most interesting biomarker UPK2 obtained from the TCGA analysis in the Oncomine database and evaluated its impact on prognosis. We collected 132 blood samples from patients with early-stage lung adenocarcinoma who were tested the expression level of free mRNA in the plasma.Results: The results revealed that UPK2, KLHDC3, GALR2 and TYRP1 occupied a central position in the co-expression network which were also significantly correlated with the survival of patients. The expression level of free UPK2 in the plasma relative to GADPH in non-relapsed patients was 0.1623, and in relapsed patients, it was 0.2763. ROC was used to evaluate the effectiveness of free UPK2 mRNA in the blood for monitoring postoperative recurrence, with an AUC of 0.767 and a 95% confidence interval of 0.675-0.858. At the same time, patients with high expression of free UPK2 mRNA had significantly poorer survival than those with low expression of UPK2. Conclusions: The expression level of free UPK2 mRNA in plasma has the potential as an indicator of postoperative recurrence in patients with early LUAD. This may have guiding significance for the subsequent clinical treatment of patients.

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