Potential Biomarker For Lung Cancer Research Articles

CLEC3B Identified as a Potential Lung Cancer Biomarker in Serum by Aptamer‐Capture Technology

AbstractLung cancer is the first malignant tumor with morbidity and mortality in the world. To identify a novel lung cancer biomarker facilitating early detection lung cancer, we had obtained a nucleic acid aptamer (Apt‐5) that specifically recognized lung cancer serum. An affinity purification experiment by using magnetic nanoparticles was used to pull down the target proteins, protein CLEC3B was subsequently identified as the target of the aptamer Apt‐5 by MS analysis. The aptamer Apt‐5 displayed high affinity to the CLEC3B protein with a dissociation constant (KD) of 23.9±5.5 nM by SPR. The specificity and selectivity of the CLEC3B protein with the aptamer Apt‐5 were verified by EMSA. It was further confirmed by ELISA experiments that the average concentration of CLEC3B in lung cancer serum was higher than that in healthy human serum (3.272±0.1732 ng/mL vs. 2.104±0.1174 ng/mL, P<0.001.). Moreover, the sensitivity and specificity of ELISA assay in this study are 90 % and 80 %, respectively. So the protein CLEC3B might serve as a potential lung cancer biomarker for early diagnosis and therapy.

Long non-coding RNA FAM201A promotes lung squamous cell carcinoma progression through interaction with miR-101.

This study aimed to investigate the mechanism of LncRNA FAM201A mediating lung squamous cell carcinoma progression through interaction with miR-101. NCI-H520 cells and SK-MES-1 cells were transfected with miRNA-101-mimics and miRNA-101-inhibitor, the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect FAM201A and miR-101 expression. CCK-8, Wound healing assay and transwell assay were utilized to detect the influence of FAM201A on the malignancy of NCI-H520NCI-H520 and SK-MES-1SK-MES-1 cells. Cell apoptosis was determined by flow cytometry. The underlying pathways of FAM201A were measured using Western blot. Xenograft tumor experiments were conducted to detect tumor growth and metastasis in vivo.NCI-H520SK-MES-1 Kaplan-Meier method calculated patient survival. (1) Silencing of FAM201A inhibited the proliferation, migration and invasion of NCI-H520 and SK-MES-1cells and stimulated cell apoptosis significantly. Furthermore, FAM201A elimination hindered tumor growth and metastasis in vivo. (2) Compared with the si-control group, the protein expression of Ki67, Vimentin, Cleaved-caspase-3 and N-cadherin were decreased in the si-FAM201A group. (3) After transfection of miR-101-mimics, the expression level of Vimentin protein was significantly increased, while the expression level of Vimentin protein was significantly decreased after miR-101-inhibitor transfection. (4) MiR-101 mimics could alleviate FAM201A silencing-induced inhibitive effects on cell proliferation, migration, invasion and promotive effects on cell apoptosis. FAM201A could target miR-101 and upregulate Vimentin to inhibit lung cancer progression. FAM201A was expected to be a potential biomarker and therapeutic target for lung cancer.

Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer.

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) degrade tryptophan (Trp) into kynurenine (Kyn) at the initial step of an enzymatic pathway affecting T cell proliferation. IDO1 is highly expressed in various cancer types and associated with poor prognosis. Nevertheless, the serum Kyn/Trp concentration ratio has been suggested as a marker of cancer-associated immune suppression. We measured Kyn and Trp in blood samples of a wide cohort of non-small-cell lung cancer (NSCLC) patients, before they underwent surgery, and analyzed possible correlations of the Kyn/Trp ratio with either IDO1 expression or clinical–pathological parameters. Low Kyn/Trp significantly correlated with low IDO1 expression and never-smoker patients; while high Kyn/Trp was significantly associated with older (≥68 years) patients, advanced tumor stage, and squamous cell carcinoma (Sqcc), rather than the adenocarcinoma (Adc) histotype. Moreover, high Kyn/Trp was associated, among the Adc group, with higher tumor stages (II and III), and, among the Sqcc group, with a high density of tumor-infiltrating lymphocytes. A trend correlating the high Kyn/Trp ratio with the probability of recurrences from NSCLC was also found. In conclusion, high serum Kyn/Trp ratio, associated with clinical and histopathological parameters, may serve as a serum biomarker to optimize risk stratification and therapy of NSCLC patients.

Potential Prospective Biomarkers for Non-small Cell Lung Cancer: Mini-Chromosome Maintenance Proteins.

Minichromosome maintenance proteins (MCMs) are considered to be essential factors coupling DNA replication to both cell cycle progression and checkpoint regulation. Previous studies have shown that dysregulation of MCMs are implicated in tumorigenesis of lung cancer. However, the distinct expression/mutation patterns and prognostic values of MCMs in lung cancer have yet to be systematically elucidated. In the present study, we analyzed the transcriptional levels, mutations, and prognostic value of MCM1-10 in non-small cell lung cancer (NSCLC) patients using multiple bioinformatics tools, including ONCOMINE, GEPIA, Kaplan–Meier Plotter, cBioPortal, and GESA. The analysis results from GEPIA dataset showed that MCM2/4/10 was significantly high expressed in both lung adenocarcinoma (LUAD) and squamous cell lung carcinomas (LUSCs). Meanwhile, the expression levels of MCM2/4/6/7/8 were associated with advanced tumor stages. Subsequent survival analysis using the Kaplan–Meier Plotter indicated that high expression levels of MCM1/2/3/4/5/6/7/8/10 were associated with worse overall survival (OS), while high expression level of MCM9 predicted better OS in these patients. Furthermore, we experimentally validated overexpression of MCM2 and MCM4 in NSCLC, thus the results from this study support a view that they may serve as potential prospective biomarkers to identify high-risk subgroups of NSCLC patients.

Regulatory function of peroxiredoxin I on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung cancer development.

Smoking is a major cause of lung cancer, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most important carcinogens in cigarette smoke. NNK modulates the expression of peroxiredoxin (Prdx) I in lung cancer. Prdx1 is upregulated in lung squamous cell carcinoma and lung adenocarcinoma, and considered a potential biomarker for lung cancer. The current article reviewed the role and regulatory mechanisms of Prdx1 in NNK-induced lung cancer cells. Prdx1 protects erythrocytes and DNA from NNK-induced oxidative damage, prevents malignant transformation of cells and promotes cytotoxicity of natural killer cells, hence suppressing tumor formation. In addition, Prdx1 has the ability to prevent NNK-induced lung tumor metabolic activity and generation of large amount of reactive oxygen species (ROS) and ROS-induced apoptosis, thus promoting tumor cell survival. In contrast to this, Prdx1, together with NNK, can promote the epithelial-mesenchymal transition and migration of lung tumor cells. The signaling pathways associated with NNK and Prdx1 in lung cancer cells have been discussed in present review; however, numerous potential pathways are yet to be studied. To develop novel methods for treating NNK-induced lung cancer, and improve the survival rate of patients with lung cancer, further research is needed to understand the complete mechanism associated with NNK.

RUNX2 as a Potential Prognosis Biomarker and New Target for Human Lung Cancer

Background and objectivesThe role of runt-related transcription factor 2 (RUNX2) in tumorigenesis and tumor progression in many cancers has been identified except for lung cancer. This study aimed to explore the expression level, functions and prognostic values of RUNX2 in lung cancer.

CD5L as an Extracellular Vesicle-Derived Biomarker for Liquid Biopsy of Lung Cancer.

Cancer screening and diagnosis can be achieved by analyzing specific molecules within serum-derived extracellular vesicles (EVs). This study sought to profile EV-derived proteins to identify potential lung cancer biomarkers. EVs were isolated from 80 serum samples from healthy individuals and cancer patients via polyethylene glycol (PEG)-based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM. Proteomic analysis was performed using 2-D gel electrophoresis and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI–TOF MS). The expression of proteins that were differentially upregulated in the EVs or tissue of lung cancer samples was validated by Western blotting. The area under the curve (AUC) was calculated to assess the predictability of each differentially expressed protein (DEP) for lung cancer. A total of 55 upregulated protein spots were selected, seven of which (CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3) were found to be expressed at high levels in patient-derived EVs by Western blotting. Meanwhile, only the expression of EV CD5L correlated with that in cancer tissues. CD5L also demonstrated the highest AUC value (0.943) and was found to be the core regulator in a pathway related to cell dysfunction. Cumulatively, these results show that EV-derived CD5L may represent a potential biomarker—detected via a liquid biopsy—for the noninvasive diagnosis of lung cancer.

Serum Exosomes and Their miRNA Load-A Potential Biomarker of Lung Cancer.

Simple SummaryExosomes are an emerging source of cancer biomarkers. Molecular components of serum-derived exosomes have been addressed in several reports in the context of biomarkers for early detection of lung cancer. However, despite the promising results of pilot studies, the clinical applicability of such biomarkers has not been validated yet. In this review, the diagnostic potential of miRNA content of serum-derived exosomes is presented. Moreover, potential target genes and signaling pathways affected by miRNA present in lung cancer signatures are discussed.Early detection of lung cancer in screening programs is a rational way to reduce mortality associated with this malignancy. Low-dose computed tomography, a diagnostic tool used in lung cancer screening, generates a relatively large number of false-positive results, and its complementation with molecular biomarkers would greatly improve the effectiveness of such programs. Several biomarkers of lung cancer based on different components of blood, including miRNA signatures, were proposed. However, only a few of them have been positively validated in the context of early cancer detection yet, which imposes a constant need for new biomarker candidates. An emerging source of cancer biomarkers are exosomes and other types of extracellular vesicles circulating in body fluids. Hence, different molecular components of serum/plasma-derived exosomes were tested and showed different levels in lung cancer patients and healthy individuals. Several studies focused on the miRNA component of these vesicles. Proposed signatures of exosome miRNA had promising diagnostic value, though none of them have yet been clinically validated. These signatures involved a few dozen miRNA species overall, including a few species that recurred in different signatures. It is worth noting that all these miRNA species have cancer-related functions and have been associated with lung cancer progression. Moreover, a few of them, including known oncomirs miR-17, miR-19, miR-21, and miR-221, appeared in multiple miRNA signatures of lung cancer based on both the whole serum/plasma and serum/plasma-derived exosomes.

Biglycan, tumor endothelial cell secreting proteoglycan, as possible biomarker for lung cancer

ObjectivesIn lung cancer, surgery remains the most curative treatment and limited resection is beneficial for patients with low cardiopulmonary function and low malignancy tumors. However, there are no biomarkers of low malignancy to select candidates for limited resection without compromising the outcome of treatments. Recently we identified biglycan (BGN) as a tumor endothelial cell (TEC) marker that is associated with tumor progression in various cancers. In this study, we analyzed the association between BGN expression in TECs in lung cancer and cancer progression in patients.Materials and MethodsFirst, we performed immunohistochemistry of BGN with resected lung tumor tissues of 155 patients who had undergone thoracic surgery and analyzed the correlation between BGN‐positive vessel density in primary lung tumors and clinicopathological factors. Second, we measured the BGN levels in preoperative serum of other 46 patients with lung cancer by ELISA, and analyzed the correlation between BGN expression in tumor tissues and blood BGN levels.ResultsHigh BGN expression in the TECs was significantly associated with T factor, and was a significant negative predictor. BGN levels in preoperative serum of 46 patients with lung cancer was significantly correlated with BGN expression in the TECs. Preoperative serum BGN level was significantly lower in healthy volunteers and less invasive adenocarcinoma than in invasive adenocarcinoma and other lung carcinomas. These results suggest that low BGN level in preoperative serum in patients with lung cancer might indicate low malignancy.ConclusionsBGN can be a potential biomarker for lung cancer.

Musashi 2 (MSI2) expression as an independent prognostic biomarker in non-small cell lung cancer (NSCLC).

BackgroundMusashi-2 (MSI2) is a member of RNA-binding protein family that regulates mRNA translation of numerous intracellular targets and influences maintenance of stem cell identity. This study assessed MSI2 as a potential clinical biomarker in non-small cell lung cancer (NSCLC).MethodsThe current study included 40 patients with NSCLC, of whom one presented with stage 1, 14 presented with stage II, 15 presented with stage III, and 10 patients had stage IV. All patients received standard of care treatments. All patient samples were obtained before treatment started. We used immunohistochemical (IHC) approach to measure MSI2 protein expression in matching specimens of normal lung versus tumor tissues, and primary versus metastatic tumors, followed by correlative analysis in relation to clinical outcomes. In parallel, clinical correlative analysis of MSI2 mRNA expression was performed in silico using publicly available datasets (TCGA/ICGC and KM plots).ResultsMSI2 protein expression in patient samples was significantly elevated in NSCLC primary tumors versus normal lung tissue (P=0.03). MSI2 elevated expression positively correlated with a decreased progression free survival (PFS) (P=0.026) combined for all stages and with overall survival (OS) at stage IV (P=0.013). Elevated MSI2 expression on RNA level was confirmed in primary tumor versus normal tissue samples in TCGA dataset (P<0.0001), and positively correlated with decreased OS (P=0.02). No correlation was observed between MSI2 expression and age, sex, smoking, and treatment type.ConclusionsElevated MSI2 expression in primary NSCLC tumors is associated with poor prognosis and can be used as a novel potential prognostic biomarker in NSCLC patients. Future studies in an extended patient cohort are warranted.

TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction.

Platelets contain a rich repertoire of RNA species, such as mRNAs and long non-coding RNAs. During the development of tumors, platelets are "educated" by cancer cells, altering their transcriptome and molecular content, thereby, tumor educated platelet (TEP) lncRNA profile has the potential to diagnose lung cancer. The current study was aimed to examine whether TEPs might be a potential biomarker for lung cancer. Platelet precipitation was obtained by low-speed centrifugation. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 were selected by lncRNA microarray and validated by qPCR in a large cohort of lung cancer patients and healthy donors. Besides, we analyzed the association of their expression levels with clinicopathological features. TEP linc-GTF2H2-1 and RP3-466P17.2 were significantly downregulated, while lnc-ST8SIA4-12 was significantly upregulated in patients with lung cancer or with early-stage lung cancer as compared to healthy donors, possessing AUCs of 0.781, 0.788, 0.725 for lung cancer and 0.704, 0.771, 0.768 for early-stage lung cancer, respectively. Notably, their combination demonstrated the markedly elevated AUCs of 0.921 for lung cancer and 0.895 for early-stage lung cancer. Besides, the combination of TEP linc-GTF2H2-1 was capable to facilitate diagnostic efficiencies of CEA, Cyfra21-1, or NSE to distinguish advanced-stage lung cancer patients from early ones, with an AUC of 0.899 based on the integration of these four factors. Our data suggested that lncRNAs sequestered in TEPs enabled blood-based lung cancer diagnosis and progression prediction.

Identification of a Lung Cancer Biomarker Using a Cancer Cell Line and Screening of Olfactory Receptors for Biomarker Detection

Several studies investigated the development of a non-invasive and early diagnostic method for cancer. Recently, the volatile organic compounds (VOCs) exhaled from cancer patients have been shown to act as a potential biomarker for cancer. However, the gas profile of breath is highly variable and not conducive to identification of biomarkers accurately. Accordingly, we identified a cancer-specific VOC as a biomarker using an in vitro cancer system in order to exclude the variables from patient condition. VOCs were collected from the headspace gas of lung cancer cell line (SK-MES) and normal lung cell line (MRC-5), followed by analysis using solid-phase microextraction (SPME)-GC/MS. As a result, 2-ethyl-1-hexanol was detected from headspace gas of SK-MES and decided as a potential biomarker for lung cancer. By screening human olfactory receptor libraries to detect a lung cancer biomarker, human olfactory receptor 4D11P (hOR4D11P) was identified as a receptor specific for 2-ethyl-1-hexanol and expressed heterologously in HEK293 cells. Additionally, we generated nanovesicles containing hOR4D11P from HEK293 cells and confirmed the expression and functionality of hOR4D11P in nanovesicles.

Investigation on Potential Correlation Between Small Nuclear Ribonucleoprotein Polypeptide A and Lung Cancer

SNRPA (small nuclear ribonucleoprotein polypeptide A) gene is essential for the pre-mRNA splicing process. Using the available datasets of TCGA or GEO, we aimed at exploring the potential association between the SNRPA gene and lung cancer by several online tools (such as GEIPA2, MEXPRESS, Oncomine) and bioinformatics analysis software (R or GSEA). SNRPA was highly expressed in the tissues of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma tissue (LUSC), compared with control tissues. The high SNRPA expression was associated with a poor survival prognosis of LUAD cases, while the genetic alteration within SNRPA was linked to the overall survival prognosis of LUSC cases. There was a potential correlation between promoter methylation and the expression of SNRPA for LUAD. Compared with normal tissues, we observed a higher phosphorylation level at the S115 site of SNRPA protein (NP_004587.1) (p = 0.002) in the primary LUAD tissues. The potential ATR kinase of the S115 site was predicted. Besides, SNRPA expression in lung cancer was negatively correlated with the infiltration level of M2 macrophage but positively correlated with that of Follicular B helper T cells, in both LUAD and LUSC. The enrichment analysis of SNRPA-correlated genes showed that cell cycle and ubiquitin mechanism-related issues were mainly observed for LUAD; however, RNA splicing-related cellular issues were mainly for LUSC. In summary, the SNRPA gene was identified as a potential prognosis biomarker of lung cancer, especially lung adenocarcinoma, which sheds new light on the association between the spliceosomal complex component and tumorigenesis.

IGFBP-4: A promising biomarker for lung cancer.

Background: Insulin-like growth factor binding protein-4 (IGFBP-4), a member of the insulin-like growth factor (IGF) family, transports, and regulates the activity of IGFs. The pregnancy-associated plasma protein-A (PAPP-A) has proteolytic activity towards IGFBP-4, and both proteins have been associated with a variety of cancers, including lung cancer. Thus, we aimed to evaluate the use of IGFBP-4 and PAPP-A as potential biomarkers for lung cancer. Methods: Eighty-three volunteers, including 60 patients with lung cancer and 23 healthy individuals, were included in this study. The patients with lung cancer were selected based on their treatment status, histological subgroup, and stage of the disease. Enzyme-linked immunosorbent assays were used to assess the serum levels of IGFBP-4 and PAPPA, whereas the IGF-1 levels were measured using a chemiluminescent immunometric assay. Results: The serum IGFBP-4 levels in all patient groups, regardless of the treatment status and histological differences, were significantly higher than those in the control group (p<0.005). However, the serum PAPP-A levels in the untreated patient group were found to be higher than those in the control group, but this difference was not statistically significant (p=0.086). Conclusions: The serum PAPP-A and IGFBP-4 levels are elevated in lung cancer. However, IGFBP-4 may have better potential than PAPP-A as a lung cancer biomarker.

CXCR4 uses STAT3-mediated slug expression to maintain radioresistance of non-small cell lung cancer cells: emerges as a potential prognostic biomarker for lung cancer

Lung cancer is one of the most common reasons for cancer-induced mortality across the globe, despite major advancements in the treatment strategies including radiotherapy and chemotherapy. Existing reports suggest that CXCR4 is frequently expressed by malignant tumor and is imperative for vascularization, tumor growth, cell migration, and metastasis pertaining to poor prognosis. In this study, we infer that CXCR4 confers resistance to ionizing radiation (IR) in nonsmall cell lung cancer (NSCLC) cells. Further, on the basis of colony forming ability, one finds that drug-resistant A549/GR cells with improved CXCR4 expression exhibited more resistance to IR than A549 cells evidenced along with a reduction in the formation of γ-H2AX foci after IR. Transfection of shRNA against CXCR4 or treatment of pharmacological inhibitor (AMD3100) both led to sensitization of A549/GR cells towards IR. Conversely, the overexpression of CXCR4 in A549 and H460 cell lines was found to improve clonogenic survival, and reduce the formation of γ-H2AX foci after IR. CXCR4 expression was further correlated with STAT3 activation, and suppression of STAT3 activity with siSTAT3 or a specific inhibitor (WP1066) significantly stymied the colony-forming ability and increased γ-H2AX foci formation in A549/GR cells, indicating that CXCR4-mediated STAT3 signaling plays an important role for IR resistance in NSCLC cells. Finally, CXCR4/STAT3 signaling was mediated with the upregulation of Slug and downregulation of the same with siRNA, which heightened IR sensitivity in NSCLC cells. Our data collectively suggests that CXCR4/STAT3/Slug axis is paramount for IR resistance of NSCLC cells, and can be regarded as a therapeutic target to enhance the IR sensitivity of this devastating cancer.

The Relationship between Lymphocyte Subsets and the Prognosis and Genomic Features of Lung Cancer: A Retrospective Study.

Background: It has been shown that the prognosis of malignant tumors was closely related to the composition and function of immune system, which was associated with genomic features. However, the prognostic value of peripheral T lymphocyte subsets and its relationship with genomic features in lung cancer has not been analyzed extensively. Therefore, this study was intended to evaluate the relationship between lymphocyte subsets and the prognosis and genomic features of lung cancer.Methods: 598 lung cancer patients with complete data were included in this study between 2011 and 2018. Kaplan-Meier method and Pearson analyses were conducted to study the prognostic value of CD3+, CD4+, CD8+ T lymphocytes and the rate of CD4/CD8.Results: Patients with EGFR mutation has lower mean percentage of CD8+ lymphocytes than patients with EGFR wild-type (24.71 versus 26.62, respectively, P=0.041). Patients with high CD3 had better OS than those with low (27 versus 14 months, P=0.002). Patients with higher CD4 and CD4/CD8 rate had longer OS than with lower (27 versus 12 months, P=0.002; 25 versus 9 months, P=0.008, respectively). Patients with high CD8 had poor PFS than low group (6 versus 11 months, P=0.009). There was a negative correlation between CD3+ and CD4+ cells and OS in smoking stage Ⅱ female lung cancer patients (PCC = 0.626, P<0.05; PCC = 0.534, P<0.05, respectively). In stage Ⅰ male lung cancer patients, CD8+T cell is negatively correlated with OS and PFS (PCC = 0.295, P<0.05; PCC = 0.280, P<0.05, respectively)Conclusions: Lung cancer patients with EGFR mutation had lower percentage of CD8+ lymphocytes. Lymphocyte subsets might be potential prognostic biomarkers of lung cancer, but they are affected by gender and tumor stage.

Bioinformatics Analysis Reveals Centromere Protein K Can Serve as Potential Prognostic Biomarker and Therapeutic Target for Non-small Cell Lung Cancer

Background:: Non-small cell lung carcinoma (NSCLC) accounts for 80% of all lung cancer cases, which have been a leading cause of morbidity and mortality worldwide. Previous studies demonstrated that centromere proteins were dysregulated and involved in regulating the tumorigenesis and development of human cancers. However, the roles of centromere protein family members in NSCLC remained to be further elucidated. Objective:: The present study aimed to explore the roles of centromere protein family members in NSCLC. Method:: GEPIA (http://gepia.cancer-pku.cn/) was used to analyze the target’s expression between normal and human cancers. We explored the prognostic value of centromere proteins in NSCLC using the Kaplan–Meier plotter (http://kmplot.com). The protein-protein interaction among centromere proteins were determined using GeneMANIA (http://www.genemania.org). TISIDB (http://cis.hku.hk/TISIDB) database was used to detect the relationship between centromere proteins expression and clinical stages, lymphocytes, immunomodulators and chemokines in NSCLC. The DAVID database (https://david.ncifcrf.gov) was used to detect potential roles of CENPK using its co-expressing genes Results:: The present study for the first time showed that centromere protein family members including CENPA, CENPF, CENPH, CENPI, CENPK, CENPM, CENPN, CENPO, CENPQ, CENPU were dysregulated and correlated to the poor prognosis of patients with LUAD. CENPK showed the greatest correlation with the prognosis of patients with NSCLC. We found that CENPK was significantly highly expressed in LUAD samples and overexpression of CENPK was remarkably correlated to the shorter OS and DFS on patients with different stage NSCLC. Of note, this study for the first time showed that CENPK was significantly correlated to the lymphocytes and immunomodulators using the TISIDB database Conclusion:: In summary, CENPK can serve as a novel biomarker for the diagnosis of patients with NSCLC.

Long non-coding RNA (lncRNA) PGM5P4-AS1 inhibits lung cancer progression by up-regulating leucine zipper tumor suppressor (LZTS3) through sponging microRNA miR-1275

ABSTRACT It is necessary to explore new molecules for the improvement of precise diagnosis and antitumor therapies in lung cancer. LncRNAs (long non-coding RNAs) play an important role in the regulation of cancer cell malignant behavior and tumor development. In this work, we found that a newly discovered lncRNA, lncRNA PGM5P4-AS1, was lower expressed in lung cancer tissues than adjacent tissues. Then, the lncRNA PGM5P4-AS1 was overexpressed or knocked-down in different lung cancer cells, and its effects on the malignant phenotypes were measured by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, wound healing assay, and transwell assay. The results showed that the overexpression of PGM5P4-AS1 inhibited lung cancer cell proliferation, migration, and invasion activities, while these abilities were prominently promoted by the interference of PGM5P4-AS1. Further, the growth of lung cancer tumors in nude mice was also inhibited by PGM5P4-AS1 overexpression. In mechanism, PGM5P4-AS1 has the binding site of miR-1275 and could positively regulate the expression of LZTS3 via sponging miR-1275. In conclusion, PGM5P4-AS1 could be a potential precise diagnosis and therapeutic target biomarker of lung cancer.

Identification of potential immune-related prognostic biomarkers of lung cancer using gene co-expression network analysis*

Abstract Objective The objective of this study was to identify new carcinogenetic hub genes and develop the integration of differentially expressed genes to predict the prognosis of lung cancer. Methods GSE139032 microarray data packages were downloaded from the Gene Expression Omnibus for planning, testing, and review of data. We identified KRT6C, LAMC2, LAMB3, KRT6A, and MYEOV from a key module for validation. Results We found that the five genes were related to a poor prognosis, and the expression levels of these genes were associated with tumor stage. Furthermore, Kaplan-Meier plotter showed that the five hub genes had better prognostic values. The mean levels of methylation in lung adenocarcinoma (LUAD) were significantly lower than those in healthy lung tissues for the hub genes. However, gene set enrichment analysis (GSEA) for single hub genes showed that all of them were immune-related. Conclusion Our findings demonstrated that KRT6C, LAMC2, LAMB3, KRT6A, and MYEOV are all candidate diagnostic and prognostic biomarkers for LUAD. They may have clinical implications in LUAD patients not only for the improvement of risk stratification but also for therapeutic decisions and prognosis prediction. Abbreviations: LUAD, lung adenocarcinoma; GSEA, gene set enrichment analysis; NSCLC, non-small-cell lung cancer; WGCNA, weighted gene co-expression network analysis; MEs, module eigengenes; GS, gene significance; MS, module significance; KEGG, Kyoto Encyclopedia of Genes and Genomes; GO, gene ontology; CC, cellular component; MF, molecular function; BP, biological process; GEPIA, gene expression profiling interactive analysis; HPA, Human Protein Atlas; TIMER, Tumor Immune Estimation Resource; TCGA, The Cancer Genome Atlas; OS, overall survival; PF, first progression; PPS, post-progression survival; IHC, immunohistochemical

Electrochemical Biosensors Integrating Metallic and Non-Metallic Nanomaterials for Biomedical Applications

In this talk, I will present our latest efforts made on creating highly sensitive and selective electrochemical biosensors integrating either carbon nanotubes or gold nanoparticles in addition to biological molecules or polyelectrolytes for medical diagnostic applications. Single or multi-walled carbon nanotubes and graphenes wrapped with polyelectrolytes were implemented onto screen printed carbon electrode (SPCE) surfaces for enhancing the sensors sensitivity. Whereas target analyte selective enzymes were utilized to improve the selectivity. The oppositely charged polyelectrolyte coated carbon nanomaterials and enzymes were immobilized on the electrode surface via a simple layer by layer assembly process. Our interest of analytes were hypoxanthine, xanthine, uric acid, dopamine and serotonin, which can be used for diagnosis of various diseases including cardiovascular disorders and game addiction syndrome. The developed biosensors were successfully applied to both normal and patient serum analyses. In addition, a brief introduction of utilizing target selective DNA aptamer coated gold nanoparticles deposited on SPCE for the selective voltammetric detection of protein tyrosine kinase-7, which is known to be a potential lung cancer biomarker. Finally, I will discuss future aspects and challenging issues of our nanomaterial integrated biosensing methodologies.