Dataset Information

Elevated Heterogeneous Nuclear Ribonucleoprotein C Expression Correlates With Poor Prognosis in Patients With Surgically Resected Lung Adenocarcinoma.

ABSTRACT:

Background

Lung adenocarcinoma (LUAD), as the most common histological subtype of lung cancer, is a high-grade malignancy and a leading cause of cancer-related death globally. Identification of biomarkers with prognostic value is of great significance for the diagnosis and treatment of LUAD. Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an RNA-binding protein "reader" of N6-methyladenosine (m⁶A) methylation, and is related to the progression of various cancers; however, its role in LUAD is unclear. The aims of this study aims were to study the expression and prognostic value of HNRNPC in LUAD.

Methods

The Oncomine database and gene expression profiling interactive analysis (GEPIA) were used for preliminary exploration of HNRNPC expression and prognostic value in LUAD. LUAD cases from The Cancer Genome Atlas (TCGA) (n = 416) and the Kaplan-Meier plotter database (n = 720) were extracted to study the differential expression and prognostic value of HNRNPC. HNRNPC expression in the National Cancer Center of China (NCC) cohort was analyzed by immunohistochemical staining, and the relationship between HNRNPC expression and survival rate evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Several pathways that were significantly enriched in the HNRNPC high expression group were identified by Gene Set Enrichment Analysis (GSEA).

Results

Five data sets from the Oncomine and GEPIA databases all supported that HNRNPC expression is significantly higher in LUAD than in normal lung tissue. In TCGA cohort, HNRNPC was highly expressed in LUAD tissues and significantly related to age, sex, smoking history, ethnicity, lymph node metastasis, and TNM staging (P < 0.001). High HNRNPC expression was significantly correlated with poor prognosis in the three cohorts (NCC, TCGA, and K-M plotter) (P < 0.05). Multivariate Cox regression analysis showed that HNRNPC expression was an independent prognostic factor in both TCGA and NCC cohorts (P < 0.05). Further, 10 significantly enriched pathways were identified from TCGA data and 118 lung cancer cell lines in CCLE, respectively.

Conclusions

High HNRNPC expression is significantly related to poor overall survival in patients with LUAD, suggesting that HNRNPC may be a cancer-promoting factor and a potential prognostic biomarker in LUAD.

SUBMITTER: Guo W

PROVIDER: S-EPMC7868529 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Elevated Heterogeneous Nuclear Ribonucleoprotein C Expression Correlates With Poor Prognosis in Patients With Surgically Resected Lung Adenocarcinoma.

Guo Wei W Huai Qilin Q Zhang Guochao G Guo Lei L Song Peng P Xue Xuemin X Tan Fengwei F Xue Qi Q Gao Shugeng S He Jie J

Frontiers in oncology 20210125

<h4>Background</h4>Lung adenocarcinoma (LUAD), as the most common histological subtype of lung cancer, is a high-grade malignancy and a leading cause of cancer-related death globally. Identification of biomarkers with prognostic value is of great significance for the diagnosis and treatment of LUAD. Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an RNA-binding protein "reader" of N6-methyladenosine (m<sup>6</sup>A) methylation, and is related to the progression of various cancers; however ...[more]

PMID: 33569346

Similar Datasets

Project description:BackgroundElevated Small Nuclear Ribonucleoprotein Polypeptide A (SNRPA) can enhance tumor cell growth and proliferation in various cancers. However, rarely studies focus on the comprehensive analysis of SNRPA in hepatocellular carcinoma (HCC).MethodsTCGA and GEO databases were used to analyze the mRNA expression of SNRPA in HCC. Protein expression of SNAPA was validated using immunohistochemistry. Stably transfected HCC cells were used to investigate the role of SNRPA in the progression of HCC. The functional enrichment analysis was utilized for the biological function prediction. The CIBERSORT and ssGSEA algorithms were used to evaluate the composition of the tumor microenvironment and immunocyte infiltration ratio.ResultsThe SNRPA expression was upregulated in HCC and positively correlated with tumor stage and grade. SNRPA overexpression were independent risk factors for poor overall survival (OS) and recurrence-free survival (RFS). In patients with early-stage disease, low alpha-fetoprotein expression, and better differentiation, SNRPA still exhibited the excellent prognostic value. Knockdown of SNRPA inhibited the proliferation and migration while promoting the apoptosis of HCC cells. Higher methylation of the CpG site cg16596691 correlated with longer OS in HCC patients. Genes co-expressed with SNRPA were overexpressed in HCC and correlated with shorter OS. The GO and KEGG enrichment analysis showed that SNRPA expression was related to mRNA splicing, spliceosome signaling. GSEA demonstrated that the main enrichment pathway of SNRPA-related differential genes was spliceosome signaling, cell cycle signaling, P53 signaling pathway, T cell receptor signaling pathway, natural killer cell-mediated signaling. CIBERSORT and ssGSEA algorithm revealed that SNRPA was mainly associated with the higher proportion of CD8+T cells, T cells follicular helper, T cells regulatory, Macrophages M0, and the lower proportion of T cells CD4 memory resting, NK cells resting, Monocytes, and Mast cells resting.ConclusionElevated SNRPA enhances tumor cell proliferation and correlated with poor prognosis and immune infiltrates in patients with HCC.

Project description:Background: Lung cancer has the highest morbidity and mortality of cancers worldwide. Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer and surgery is its most common treatment. The dysregulated expression of DNA repair genes is found in a variety of cancers and has been shown to affect the origin and progression of these diseases. However, the function of DNA repair genes in surgically-treated LUAD is unclear.Methods: We sought to determine the association between the signature of DNA repair genes for patients with surgical LUAD and their overall prognosis. We obtained gene expression data and corresponding clinical information of LUAD from The Cancer Genome Atlas (TCGA) database. The differently expressed DNA repair genes of surgically-treated LUAD and normal tissues were identified using the Wilcoxon rank-sum test. We used uni- and multivariate Cox regression analyses to shrink the aberrantly expressed genes, which were then used to construct the prognostic signature and the risk score formula associated with the independent prognosis of surgically-treated LUAD. We used Kaplan-Meier and Cox hazard ratio analyses to confirm the diagnostic and prognostic roles. Two validation sets (GSE31210 and GSE37745) were downloaded from the Gene Expression Omnibus (GEO) and were used to externally verify the prognostic value of the signature. OSluca online database verifies the hazard ratio for the DNA repair genes by which the signature was constructed. We investigated the correlation between the signature of the DNA repair genes and the clinical parameters. The potential molecular mechanisms and pathways of the prognostic signature were explored using Gene Set Enrichment Analysis (GSEA).Results: We determined the prognostic signature based on six DNA repair genes (PLK1, FOXM1, PTTG1, CCNO, HIST3H2A, and BLM) and calculated the risk score based on this formula. Patients with surgically-treated LUAD were divided into high-risk and low-risk groups according to the median risk score. The high-risk group showed poorer overall survival than the low-risk group; the signature was used as an independent prognostic indicator and had a greater prognostic value in surgically-treated LUAD. The prognostic value was replicated in GSE31210 and GSE37745. OSluca online database analysis shows that six DNA repair genes were associated with poor prognosis in most lung cancer datasets. The prognostic signature risk score correlated with the pathological stage and smoking status in surgically-treated LUAD. The GSEA of the risk signature in high-risk patients showed pathways associated with the cell cycle, oocyte meiosis, mismatch repair, homologous recombination, and nucleotide excision repair.Conclusions: A six-DNA repair gene signature was determined using TCGA data mining and GEO data verification. The gene signature may serve as a novel prognostic biomarker and therapeutic target for surgically-treated LUAD.

Dataset Information

Elevated Heterogeneous Nuclear Ribonucleoprotein C Expression Correlates With Poor Prognosis in Patients With Surgically Resected Lung Adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

Elevated Heterogeneous Nuclear Ribonucleoprotein C Expression Correlates With Poor Prognosis in Patients With Surgically Resected Lung Adenocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets