Dataset Information

Differentially Expressed Genes Associated With Prognosis in Locally Advanced Lymph Node-Negative Prostate Cancer.

ABSTRACT: Older age is one of the main risk factors for cancer development. The incidence of prostate cancer, as a multifactorial disease, also depends upon demographic factors, race, and genetic predisposition. Prostate cancer most frequently occurs in men over 60 years of age, indicating a clear association between older age and disease onset. Carcinogenesis is followed by the deregulation of many genes, and some of these changes could serve as biomarkers for diagnosis, prognosis, prediction of drug therapy efficacy, as well as possible therapeutic targets. We have performed a bioinformatic analysis of a The Cancer Genome Atlas (TCGA) data and RNA-Seq profiling of a Russian patient cohort to reveal prognostic markers of locally advanced lymph node-negative prostate cancer (lymph node-negative LAPC). We also aimed to identify markers of the most common molecular subtype of prostate cancer carrying a fusion transcript TMPRSS2-ERG. We have found several genes that were differently expressed between the favorable and unfavorable prognosis groups and involved in the enriched KEGG pathways based on the TCGA (B4GALNT4, PTK6, and CHAT) and Russian patient cohort data (AKR1C1 and AKR1C3). Additionally, we revealed such genes for the TMPRSS2-ERG prostate cancer molecular subtype (B4GALNT4, ASRGL1, MYBPC1, RGS11, SLC6A14, GALNT13, and ST6GALNAC1). Obtained results contribute to a better understanding of the molecular mechanisms behind prostate cancer progression and could be used for further development of the LAPC prognosis marker panel.

SUBMITTER: Pudova EA

PROVIDER: S-EPMC6697060 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Differentially Expressed Genes Associated With Prognosis in Locally Advanced Lymph Node-Negative Prostate Cancer.

Pudova Elena A EA Lukyanova Elena N EN Nyushko Kirill M KM Mikhaylenko Dmitry S DS Zaretsky Andrew R AR Snezhkina Anastasiya V AV Savvateeva Maria V MV Kobelyatskaya Anastasiya A AA Melnikova Nataliya V NV Volchenko Nadezhda N NN Efremov Gennady D GD Klimina Kseniya M KM Belova Anastasiya A AA Kiseleva Marina V MV Kaprin Andrey D AD Alekseev Boris Y BY Krasnov George S GS Kudryavtseva Anna V AV

Frontiers in genetics 20190809

Older age is one of the main risk factors for cancer development. The incidence of prostate cancer, as a multifactorial disease, also depends upon demographic factors, race, and genetic predisposition. Prostate cancer most frequently occurs in men over 60 years of age, indicating a clear association between older age and disease onset. Carcinogenesis is followed by the deregulation of many genes, and some of these changes could serve as biomarkers for diagnosis, prognosis, prediction of drug the ...[more]

PMID: 31447885

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Project description:Understanding the molecular mechanisms and gene expression in laryngeal squamous cell carcinoma (LSCC) may explain its aggressive biological behavior and regional metastasis pathways. In the present study, patients with locally advanced LSCC tumors were examined for differential gene expression in the normal mucosa (non-tumoral mucosa), tumors and lymph node tissues. The aim was to identify possible predictive genes for lymph node metastasis. A total of 16 patients who had undergone total laryngectomy with neck dissection for advanced LSCC were randomly selected from a hospital database: Eight of the patients had lymph node metastasis (Group 1) and the other eight patients did not have metastasis (Group 2). Overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) were analyzed. For each patient, paraffin-embedded tissue samples were collected from non-tumoral mucosa, tumoral lesions and lymph node tissues. RNA was extracted from the tissue samples and used for complementary DNA synthesis, and microarray analysis was subsequently performed on each sample. Gene expression levels were determined in each specimen, and Groups 1 and 2 were compared and statistically analyzed. The microarray results for lymph node metastasis-positive and -negative groups, indicated the differential expression of 312 genes in the lymph nodes, 691 genes in the normal mucosal tissue and 93 genes in the tumor tissue. Transgelin (TAGLN) and cofilin 1 (CFL1) were identified as possible target genes and validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The RT-qPCR results for TAGLN and CFL1 supported the microarray data. OS, DFS and DSS times were longer in Group 2 than in Group 1 (P=0.002, 0.015 and 0.009, respectively). In addition, TAGLN and CFL1 were associated with DFS and DSS. On the basis of these results, it is suggested that TAGLN and CFL1 expression may play an important role in the pathogenesis of regional metastasis and poor prognosis in advanced LSCC.

Project description:BackgroundBladder urothelial carcinoma (BLCA) is a malignant tumor of the urinary system. This study aimed to explore the potential role of lymph node metastasis-associated aberrant methylation differentially expressed genes (DEGs) in BLCA.MethodsCHAMP and limma packages were used to identify lymph node metastasis-associated aberrant methylation DEGs. Univariate Cox analysis and Lasso analysis were performed to identify the signature genes, and multivariate Cox analysis was used to construct the risk score. Subsequently, the molecular characteristics of the signature genes and the relationship between risk score and prognosis, clinical characteristics and immune cell infiltration were analyzed. The signature gene AKAP7 was selected for functional verification.ResultsA novel risk score model was constructed based on 12 signature genes. The risk score had a good ability to predict overall survival (OS). The nomogram constructed based on age, N stage and risk score had a higher value in predicting the prognosis of patients. It was also found that stromal activation in TIME may inhibit the antitumor effects of immune cells. Functional enrichment analysis revealed that ECM receptor interaction and focal adhesion were two important pathways involved in the regulation of BLCA. Immunohistochemistry showed that AKAP7 may be associated with the occurrence, clinical stages and grades, and lymph node metastasis of BLCA. In vitro cell experiments showed that the migration and invasion ability of EJ cells was significantly inhibited after AKAP7 overexpression, while the migration and invasion ability of T24 cells was significantly promoted after AKAP7 knockdown.ConclusionThe risk score model based on lymph node metastasis-associated aberrant methylation DEGs has a good ability to predict OS and is an independent prognostic factor for BLCA. It was also found that stromal activation in TIME may inhibit the antitumor effects of immune cells. This implicates aberrant methylation modifications as an important factor contributing to the heterogeneity and complexity of individual tumor microenvironments. Functional enrichment analysis revealed that ECM receptor interaction and focal adhesion were two important pathways involved in the regulation of BLCA, which contributed to the exploration of the pathological mechanism of BLCA. In addition, immunohistochemistry showed that AKAP7 may be associated with the occurrence, progression and lymph node metastasis of BLCA. In vitro cell experiments showed that AKAP7 could also inhibit the migration and invasion of cancer cells.

Dataset Information

Differentially Expressed Genes Associated With Prognosis in Locally Advanced Lymph Node-Negative Prostate Cancer.

Publications

Differentially Expressed Genes Associated With Prognosis in Locally Advanced Lymph Node-Negative Prostate Cancer.

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