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A curated target gene pool assisting disease prediction and patient-specific biomarker selection for lung squamous cell carcinoma.

ABSTRACT: There have been hundreds of genes demonstrated to be associated with lung squamous cell carcinoma (LSCC), presenting various degrees of association with this disease. In the present study, gene vectors were investigated as genetic biomarkers for the diagnosis and personalized treatment of LSCC. A LSCC genetic database (LSCC_GD) was developed through literature-associated data analysis, where 260 LSCC target genes were curated. Subsequently, numerous associations between these genes and LSCC were studied. Following this, a sparse representation-based variable selection (SRVS) was employed for gene selection from two LSCC gene expression datasets, followed by a case/control classification. Results were compared using analysis of variance (ANOVA)-based gene selection approaches. Using SRVS, a gene vector was selected from each dataset, resulting in significantly higher classification accuracy (CR), compared with randomly selected genes (For datasets GSE18842 and GSE1987, CR=100 and 100% and permutation P=5.0×10-4 and 1.8×10-3, respectively). The SRVS method outperformed ANOVA in terms of the classification ratio. The results indicated that, for a given dataset, there may be a gene vector from the 260 curated LSCC genes that possesses significant prediction power. SRVS is effective in identifying the optimum gene subset target for personalized treatment.

SUBMITTER: Huang B

PROVIDER: S-EPMC6126348 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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A curated target gene pool assisting disease prediction and patient-specific biomarker selection for lung squamous cell carcinoma.

Huang Bin B Zhong Ning N Cao Hongbao H Yu Guiping G

Oncology letters 20180731 4

There have been hundreds of genes demonstrated to be associated with lung squamous cell carcinoma (LSCC), presenting various degrees of association with this disease. In the present study, gene vectors were investigated as genetic biomarkers for the diagnosis and personalized treatment of LSCC. A LSCC genetic database (LSCC_GD) was developed through literature-associated data analysis, where 260 LSCC target genes were curated. Subsequently, numerous associations between these genes and LSCC were ...[more]

PMID: 30197682

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Project description:Objective: The purpose of this study was to investigate the miRNAs basis of tumorigenesis in LSCC, and analyze the physiological processes of target genes predicted by the screened miRNAs that may be useful for the effective therapeutic strategies. Methods: A total number of 6 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for miRNA array analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by the Affymetrix GeneChip miRNA Array 3.0 to screen effective miRNAs, then TargetScan,PITA and microRNAorg were used for target gene prediction in GeneSpring 12.5 software.Moreover, pathway-based methods were adopted to analyse physiological processes of the target genes. The screened miRNAs and the significant target genes were also validated by qRT-PCR in another 36 patients diagnosed for LSCC. Results: Analysed by the miRNAs arrays, there were seven miRNAs (hsa-miR-224, hsa-miR-183, hsa-miR-23a, hsa-miR-675, hsa-miR-27a, hsa-miR-503 and hsa-miR-4800-3p) significantly related to tumorigenesis ,and all the screened miRNAs in laryngeal squamous cell carcinoma tissues were significantly up-regulated(P<0.05). The expressions of these miRNAs were also validated by qRT-PCR. Then analysed by GeneSpring 12.5 software, there were 72 putative target genes corresponding to the seven significant miRNAs. Moreover,analysed by String database,the result indicated that most target genes could be composed of gene networks; Analysed by GO database, we observed that these target genes were involved in processes such as metabolic process, biological regulation,membrane,protein binding,ion binding and so on (P <0.05); Analysed by KEGG pathways database, MAPK signaling pathway, adherens junction and pathways in cancer played especially important role in tumorigenesis of LSCC (P<0.05). As the two important genes in MAPK signaling pathway which plays pivotal roles in tumorigenesis, FGF2 and MAP2K4 were validated by qRT-PCR, and they were significantly down-regulated(P<0.05). Conclusions: The research revealed seven miRNAs expression signature(hsa-miR-224, hsa-miR-183, hsa-miR-23a, hsa-miR-675, hsa-miR-27a, hsa-miR-503 and hsa-miR-4800-3p) of tumorigenesis in laryngeal squamous cell carcinoma,and analysed the physiological processes of the predicted target genes regulated by screened miRNAs in LSCC. The result will contribute to the understanding of the molecular basis of LSCC and help to improve the treatment. A total number of 6 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for miRNA array analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by the Affymetrix GeneChip miRNA Array 3.0 to screen effective miRNAs, then TargetScan,PITA and microRNAorg were used for target gene prediction in GeneSpring 12.5 software.Moreover, pathway-based methods were adopted to analyse physiological processes of the target genes. The screened miRNAs and the significant target genes were also validated by qRT-PCR in another 36 patients diagnosed for LSCC.

Project description:Background: Laryngeal squamous cell carcinoma (LSCC) is the most common type in head and neck squamous cell carcinoma (HNSCC), and the development of LSCC are multistep processes accompanied by changes of molecular biology. Objective: The purpose of this study was to investigate the miRNAs basis of tumorigenesis in LSCC, and analyze the microRNAs dysregulation related with the six targeted genes (CDK1,CDK2, CDK4, MCM2, MCM3, MCM4) which were related to tumorigenesis from the screened miRNAs. Methods: A total number of 5 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for miRNA array analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by the Affymetrix GeneChip miRNA Array 3.0 to screen effective miRNAs, then mirfocus 3.0 database (http://mirfocus.org/index.php) was adopted to select putative regulated miRNAs of the six targeted genes. Moreover, the selected putative regulated miRNAs were also validated by qRT-PCR in another 36 patients diagnosed for LSCC. Results: Analysed by the miRNAs arrays, there were 127 miRNAs significantly related to tumorigenesis ,and 78 showed a higher expression in tumor than in non-tumor tissue while 49 presented the contrasting pattern(P<0.01).Then analyzed by mirfocus 3.0 database, there were 2 putative regulated miRNAs, hsa-miR-24-3p and hsa-miR-183-5p, corresponding to three of the six targeted genes. Among the 2 putative miRNAs, hsa-miR-24-3p regulated MCM4,CDK1 and CDK4,while hsa-miR-183-5p regulated MCM4 only. Another miRNA we should focus on is hsa-miR-30a-5p, a tumor-suppressive factor, which was down-expressed obviously analysed by the miRNAs arrays. The expression of the 3 putative regulated miRNAs were also validated by qRT-PCR in another 36 patients (P<0.05). Conclusions: The research revealed 127 miRNAs expression signature of tumorigenesis in laryngeal squamous cell carcinoma,and analyzed 3 putative regulated miRNAs, hsa-miR-24-3p, hsa-miR-183-5p and hsa-miR-30a-5p, as potential diagnostic and therapeutic markers in LSCC. The result will contribute to the understanding of the molecular basis of LSCC and help to improve the treatment.

Project description:BackgroundNeuropilin-2 (NRP2) is a single chain transmembrane glycoprotein that acts as a co-receptor of VEGF and is related to the pathogenesis of various tumors closely. However, the clinical significance of NRP2 in oral squamous cell carcinoma (OSCC) is unclear.PurposeThe objective of this study was to investigate the role of NRP2 in the pathogenesis of OSCC and explore the associated mechanisms.Materials and methodsGEPIA (gene expression profiling interactive analysis) was used to analyze the expression of NRP2 in OSCC. Immunohistochemistry and RT-qPCR were used to detect NRP2 expression in 80 OSCC samples. The clinical correlations and prognostic significance of NRP2 expression were evaluated. In addition, the biological functions of OSCC cells transfected with shNRP2 were evaluated. The expression levels of β-catenin, C-myc, cyclin D1, and MMP-2 in Wnt/β-catenin signaling pathway were assessed by RT-qPCR after inhibiting the expression of NRP2 in SCC-25 cell line.ResultsAnalysis of cases using GEPIA revealed that NRP2 was substantially upregulated in OSCC. NRP2 expression was also significantly higher in our OSCC samples than in the controls. Elevated expression of NRP2 was correlated with lymph node metastasis (P<0.01) and distant metastasis (P<0.05) in OSCC patients, and high NRP2 levels, lymph node metastasis, and distant metastasis were associated with poor prognosis (Kaplan-Meier analysis; P<0.05). Univariate and multivariate Cox analysis showed that lymph node metastasis, distant metastasis, and NRP2 expression were independent risk factors for overall survival (OS) and disease-free survival (DFS) in OSCC patients (P<0.05). Furthermore, the proliferation, migration, and invasion of OSCC cells were inhibited by shNRP2. Following inhibiting of NRP2 expression in the SCC-25 cell line, the expression levels of β-catenin, C-myc, cyclin D1, and MMP-2 were reduced (P<0.05).ConclusionThis study shows that NRP2 functions as a tumor promoter gene in OSCC by affecting the proliferation, migration, and invasion of OSCC cells and downregulating the Wnt/β-catenin pathway. These results highlight the potential role for NRP2 as a clinical diagnostic marker.

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A curated target gene pool assisting disease prediction and patient-specific biomarker selection for lung squamous cell carcinoma.

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A curated target gene pool assisting disease prediction and patient-specific biomarker selection for lung squamous cell carcinoma.

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