Dataset Information

An Autophagy-Related Long Noncoding RNA Signature Contributes to Poor Prognosis in Colorectal Cancer.

ABSTRACT: Purpose:Colorectal cancer is one of the most common malignant primary tumors, prone to metastasis, and associated with a poor prognosis. As autophagy is closely related to the development and treatment of colorectal cancer, we investigated the potential prognostic value of long noncoding RNA (lncRNA) associated with autophagy in colorectal cancer. Methods:In this study, we acquired information on the expression of lncRNAs in colorectal cancer from the Cancer Genome Atlas (TCGA) database and found that 860 lncRNAs were associated with autophagy-related genes. Subsequently, univariate Cox regression analysis was used to investigate 32 autophagy-related lncRNAs linked to colon cancer prognosis. Subsequently, eight of the 32 autophagy-related lncRNAs (i.e., long intergenic nonprotein coding RNA 1503 [LINC01503], ZEB1 antisense RNA 1 [ZEB1-AS1], AC087481.3, AC008760.1, AC073896.3, AL138756.1, AL022323.1, and TNFRSF10A-AS1) were selected through multivariate Cox regression analysis. Based on these autophagy-related lncRNAs, a risk signature was constructed, and the patients were divided into high- and low-risk groups. Results:The high-risk group's overall survival time was significantly shorter than that of the low-risk group (p < 0.0001). Receiver operating characteristic curve analysis was performed to further confirm the validity of the model (area under the curve: 0.689). Moreover, multivariate regression suggested that the risk score was a significant prognostic risk factor in colorectal cancer. Gene set enrichment analysis showed that these gene sets are significantly enriched in cancer-related pathways, such as Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling. Conclusion:The risk signature of eight autophagy-related lncRNAs has prognostic potential for colorectal cancer. These autophagy-related lncRNAs may play a vital role in the biology of colorectal cancer.

SUBMITTER: Wei J

PROVIDER: S-EPMC7603611 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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An Autophagy-Related Long Noncoding RNA Signature Contributes to Poor Prognosis in Colorectal Cancer.

Wei Jingsun J Ge Xiaoxu X Tang Yang Y Qian Yucheng Y Lu Wei W Jiang Kai K Fang Yimin Y Hwang Maxwell M Fu Dongliang D Xiao Qian Q Ding Kefeng K

Journal of oncology 20201021

<h4>Purpose</h4>Colorectal cancer is one of the most common malignant primary tumors, prone to metastasis, and associated with a poor prognosis. As autophagy is closely related to the development and treatment of colorectal cancer, we investigated the potential prognostic value of long noncoding RNA (lncRNA) associated with autophagy in colorectal cancer.<h4>Methods</h4>In this study, we acquired information on the expression of lncRNAs in colorectal cancer from the Cancer Genome Atlas (TCGA) da ...[more]

PMID: 33149738

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Project description:Background Long noncoding RNAs (lncRNAs) are found to be novel biomarkers for hepatocellular carcinoma (HCC) and play an important role in tumor progression. We established a genomic instability-related long noncoding RNA signature (GIlncSig) as an independent prognosis factor and also investigated its impact on prognosis significance. Method Somatic mutation profiles, clinical characteristics, and RNA sequencing data were obtained from The Cancer Genome Atlas (TCGA) database. Lasso regression was used to construct GIlncSig. KEGG was used to identify the possible biological pathways. ESTIMATE and CIBERSORT algorithms were used to calculate the immune microenvironment scores and proportion of immune cells in HCC patients. The expression of LINC00501 was conducted by qRT-PCR. Cell proliferation was measured by EdU, CCK-8, and colony formation assay, and cell migration and invasion ability were measured by wound healing and transwell assay. Results 135 genomic instability-related lncRNAs were identified, and GIlncSig was constructed using 13 independent lncRNAs with significant prognosis values. Based on the GIlncSig, high-risk group had worse clinical outcomes than low-risk group, while high-risk group also had higher UBQLN4, KRAS, ARID1A, and PIK3CA expression. Moreover, the efficiency of GIlncSig combining single-gene mutation was higher than single-gene mutation alone such as TP53. The results of CIBERSORT and ESTIMATE showed that GS group and GU group had significantly different immune infiltration. In addition, LINC00501 was identified as a potential biomarker in HCC with strong relationship with clinical characteristics. In vitro assays validated that LINC00501 promoted proliferation and migration of HCC cell lines. Conclusion Our results showed that GIlncSig serves as a potential independent prognosis factor to predict HCC patients' prognosis for exploring potential mechanism and therapy strategy. Besides, LINC00501 plays an important role in the progression of HCC, which may be a potential therapy target.

Project description:BackgroundColorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide, however, the mechanisms of CRC progression remain obscure. The present study investigated the clinical significance and functional role of long noncoding RNA (lncRNA) GIHCG in CRC.MethodsExpression of GIHCG was detected by quantitative real time polymerase chain reaction (qRT-PCR) in seven CRC cell lines and 110 CRC tissues. Comparison of clinicopathological characteristics in the high GIHCG expression group and the low GIHCG expression group was performed. The overall survival (OS) and progression-free survival (PFS) of the patients were depicted with Kaplan-Meier test and compared with Log-rank test. Univariate and multivariate analyses were carried out to detect the risk factors for poor OS and PFS. In addition, expression of GIHCG was silenced with siRNAs in LoVo cells and overexpressed with pcDNA3.1-GIHCG vector in SW480 cells, respectively. And the Transwell assay, Matrigel assay, colony formation assay and Cell Counting Kit-8 assay (CCK-8) were performed to investigate the role of GIHCG in the migration, invasion and proliferation of CRC cells. Besides, the role of GIHCG in chemoresistance was also detected.ResultsGIHCG was overexpressed in seven CRC cell lines and 110 CRC tissues. High GIHCG expression was correlated with lymphovascular invasion, lymph node metastasis, distant metastasis and advanced TNM stages. Moreover, patients with high GIHCG expression had much poorer OS and PFS rates. Besides, high GIHCG expression was identified as an independent risk factor for poor OS and PFS. The Transwell assay and the Matrigel assay discovered that GIHCG deficiency inhibited cell migration and invasion, while ectopic expression of GIHCG promoted migration and invasion. Besides, the colony formation assay and the CCK-8 assay verified that GIHCG increased cell proliferation ability. By establishing 5-fluorouracil (5-FU) and Oxaliplatin (Oxa)-resistant LoVo cells and SW480 cells, we found chemoresistant CRC cells had much higher expression levels of GIHCG. Also, GIHCG facilitated cell survival under 5-FU or Oxa treatment. Furthermore, silencing of GIHCG notably reduced the improved cell survival rates of 5-FU or Oxa-resistant LoVo cells compared with control cells.ConclusionGIHCG contributes to cancer progression and chemoresistance and indicates poor prognosis in CRC. GIHCG may be a promising prognostic biomarker and therapeutic target in CRC.

Project description:BackgroundHepatocellular carcinoma (HCC), ranking as one of the most common malignant tumors, is one of the leading causes of cancer death, with a poor prognosis. Cuproptosis, a novel programmed cell death modality that has just been confirmed recently, may play an important role in HCC prognosis. Long noncoding RNA (LncRNA) is a key participant in tumorigenesis and immune responses. It may be of great significance to predict HCC based on cuproptosis genes and their related LncRNA.MethodsThe sample data on HCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Combined with cuproptosis-related genes collected from the literature search, expression analysis was carried out to find cuproptosis genes and their related LncRNAs significantly expressed in HCC. The prognostic model was constructed by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression. The feasibility of these signature LncRNAs used for the evaluation of the overall survival rate in HCC patients as independent factors was investigated. The expression profile of cuproptosis, immune cell infiltration, and the status of somatic mutation were analyzed and compared.ResultsA prognostic model of HCC consisting of seven cuproptosis gene-related LncRNA signatures was constructed. Multiple verification methods have showed that this model can accurately predict the prognosis of HCC patients. It was showed that the classified high-risk group under the risk score of this model had worse survival status, more significant expression of the immune function, and higher mutation frequency. During the analysis, the cuproptosis gene CDKN2A was found to be most closely related to LncRNA DDX11-AS1 in the expression profile of HCC patients.ConclusionThe cuproptosis-related signature LncRNA in HCC was identified, on the basis of which a model was constructed, and it was verified that it can be used to predict the prognosis of HCC patients. The potential role of these cuproptosis-related signature LncRNAs as new targets for disease therapy in antagonizing HCC development was discussed.

Dataset Information

An Autophagy-Related Long Noncoding RNA Signature Contributes to Poor Prognosis in Colorectal Cancer.

Publications

An Autophagy-Related Long Noncoding RNA Signature Contributes to Poor Prognosis in Colorectal Cancer.

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