Dataset Information

Correlation between oncogene integrator complex subunit 7 and a poor prognosis in lung adenocarcinoma.

ABSTRACT:

Background

Lung adenocarcinoma (LUAD) is one of the most common types of cancer worldwide with high incidence and mortality rates. The integrator complex subunit 7 (INTS7) encodes a subunit of the integrator complex that mediates small-nuclear ribonucleic acid (RNA) processing and has been shown to be associated with RNA polymerase II. However, the clinical significance of INTS7 in LUAD is still not clear and needs to be investigated.

Methods

The single-cell sequencing of a publicly available data set was conducted to compare the expression levels and percentages of INTS7 in lung malignant cells at different classifications and stages. Further, 33 cancer types from The Cancer Genome Atlas (TCGA) database were analyzed, protein-protein interaction (PPI) networks were constructed, and functional annotations were undertaken for the INTS7 gene. INTS7 small-interfering RNAs were transfected into LUAD cell lines, and cell biological behaviors, such as migration, invasion, apoptosis and proliferation capacity, were then examined.

Results

We found that the expression of INTS7 was significantly more upregulated in the LUAD tissues than the adjacent normal tissues. Increased INTS7 messenger RNA expression was correlated with TNM (tumor node metastasis classification) stage and gender in LUAD patients. Further, the Kaplan-Meier survival analysis indicated that LUAD patients with high INTS7 expression levels had a worse prognosis than those with low INTS7 expression levels. Finally, we found that silencing INTS7 inhibited LUAD cell viability and invasion in vitro.

Conclusions

These results suggest that INTS7 can be used as a potential therapy target and prognostic marker for LUAD. Further, INTS7 may aggravate migration and invasion, induce the proliferation, and attenuate the apoptosis capacity of cells in LUAD.

SUBMITTER: Li Z

PROVIDER: S-EPMC9840021 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Correlation between oncogene integrator complex subunit 7 and a poor prognosis in lung adenocarcinoma.

Li Zhoubin Z Zhu Pengwei P Wang Maoling M Fang Cheng C Ji Huafeng H

Journal of thoracic disease 20221201 12

<h4>Background</h4>Lung adenocarcinoma (LUAD) is one of the most common types of cancer worldwide with high incidence and mortality rates. The integrator complex subunit 7 (INTS7) encodes a subunit of the integrator complex that mediates small-nuclear ribonucleic acid (RNA) processing and has been shown to be associated with RNA polymerase II. However, the clinical significance of INTS7 in LUAD is still not clear and needs to be investigated.<h4>Methods</h4>The single-cell sequencing of a public ...[more]

PMID: 36647477

Similar Datasets

Project description:The protein phosphatase 1 regulatory subunit 3 G (PPP1R3G) participates in many tumor biological processes; however, its effects on lung adenocarcinoma (LUAD) have not been clarified. Therefore, this study aimed to explore the correlation between PPP1R3G and the prognosis and immune invasion of LUAD. We evaluated the relationship between PPP1R3G and LUAD using a wide range of databases and analysis tools, including UALCAN, TIMER, miRDB, The Human Protein Atlas and the MethSurv database. First, we explored the mRNA and protein expression levels of PPP1R3G in LUAD, and results were validated using real-time PCR. Next, we explored the relationship between PPP1R3G expression and clinical features. Finally, Kaplan-Meier curves and Cox regression were employed to investigate the prognostic significance of PPP1R3G in LUAD. In addition, we explored the relationship between the expression of PPP1R3G and immune infiltration using the TIMER database. We analyzed the relationship between PPP1R3G and methylation using MethSurv database. Results showed that PPP1R3G expression in LUAD tissues was higher than that in normal tissues, and high expression was suggestive of a poor prognosis. Moreover, PPP1R3G expression was positively correlated with the immune infiltration of CD4 + T cells, macrophages, neutrophils, and dendritic cells. PPP1R3G copy number variations also demonstrated remarkable associations with the levels of B cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells. Finally, a PPP1R3G-associated regulatory network was constructed. Overall, PPP1R3G might be a poor prognostic biomarker for LUAD and is associated with tumor immune cell infiltration.Abbreviations: LUAD: Lung adenocarcinoma; PPP1R3G: The protein phosphatase 1 regulatory subunit 3G; OS: overall survival; CI: confidence interval; CNV: copy number variance; HR: Hazard Ratio; ROC: receiver operating characteristic curve; AUC: area under the curve; TCGA: The Cancer Genome Atlas.

Project description:BackgroundInositol Polyphosphate-5-Phosphatase B (INPP5B), a inositol 5-phosphatase, plays an important role in many biological processes through phosphorylating PI(4,5)P2 and/or PI(3,4,5)P3 at the 5-position. Nevertheless, little is known about its function and cellular pathways in tumors. This study aims to investigate the potential role of INPP5B as a diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD), as well as its biological functions and molecular mechanisms in LUAD.MethodsTCGA, GEO, CTPAC, and HPA datasets were used for differential expression analysis and pathological stratification comparison. The prognostic and diagnostic role of INPP5B was determined by Kaplan-Meier curves, univariate and multivariate Cox regression analysis, and receiver operating characteristics (ROC) curve analyses. The potential mechanism of INPP5B was explored through GO, KEGG, and GSEA enrichment analysis, as well as GeneMANIA and STRING protein-protein interaction (PPI) network. PicTar, PITA, and miRmap databases were used for exploring miRNA targeting INPP5B. In molecular biology experiments, immunohistochemical analyses and Western blot analyses were used to determine protein expression. Co-immunoprecipitation assay was used to detect protein-protein interactions. CCK8 assays and colony formation assays were used for the measurement of cell proliferation. Cell cycle was assessed by PI staining with flow cytometry. Cell migration was performed by Transwell assays and wound healing assays.ResultINPP5B was decreased in LUAD tissues compared with normal adjacent tissues. And the low expression of INPP5B was associated with late-stage pathological features. In addition, INPP5B was found to be a significant independent prognostic and diagnostic factor for LUAD patients. Hsa-miR-582-5p was predicted as a negative regulator of INPP5B mRNA expression. INPP5B was significantly correlated with the expression of PTEN and the activity of PI3K/AKT signaling pathways, as determined by enrichment analysis and PPI network. In vitro experiments partially confirmed the aforementioned findings. INPP5B could interact directly with PTEN. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the AKT pathway.ConclusionOur results demonstrated that INPP5B could inhibit the proliferation and metastasis of LUAD cells. It could serve as a novel diagnostic and prognostic biomarker for LUAD patients. Trial registration LUAD tissues and corresponding para-cancerous tissues were collected from 10 different LUAD patients at Hangzhou First People's Hospital. The Ethics Committee of Hangzhou First People's Hospital has approved this study. (registration number: IIT-20210907-0031-01; registration date: 2021.09.13).

Project description:Objectives: DNA damage inducible transcript 4 (DDIT4) plays a key role in different cancers, but the role of DDIT4 in lung adenocarcinoma (LUAD) is not completely understood. The aim of this study was to evaluate the utility of DDIT4 as a prognostic biomarker for LUAD. Methods: First, DDIT4 mRNA expression in LUAD cell lines (A549, H1299 and HBE) and tissues (89 cases) was assessed by RT-PCR. Next, DDIT4 protein expression in LUAD tissues and normal tissues was assessed by immunohistochemistry (75 cases). Then, the correlation between DDIT4 expression and overall survival was analyzed using the Kaplan-Meier method. After that, we verified the utility of the DDIT4 gene as a prognostic marker of lung cancer in the TCGA database (1133 cases). Finally, the possible mechanism of the DDIT4 gene as a prognostic marker of LUAD was preliminarily explored. Results: mRNA levels of DDIT4 in HBE cells were significantly lower than in A549 and H1299 cells (P<0.05), and expression of the DDIT4 gene in cancer tissues was significantly higher than in adjacent tissues (P<0.0001). Immunohistochemical staining results showed that high expression of DDIT4 accounted for approximately 68.0% of LUAD tissues. DDIT4 expression was significantly correlated with differentiation (P < 0.05). However, it was not correlated with sex, age, smoking, tumor size, lymph node metastasis, or TNM stage (P>0.05). The survival analysis demonstrated that high DDIT4 expression was correlated with shorter overall survival (P < 0.05). Univariate and multivariate analyses indicated that DDIT4 was an independent predictor of overall survival for LUAD, which was confirmed by data from the TCGA database. Finally, we found that DDIT4 gene expression was significantly increased in the hypoxic environment compared to the normal oxygen environment, indicating that the DDIT4 gene may play an important role in the hypoxic microenvironment of tumor tissue. Conclusion: High expression levels of DDIT4 correlated with poor overall survival in patients with LUAD, and DDIT4 was an independent predictor of overall survival. These findings provide new insight for understanding the development of LUAD.

Project description:BackgroundInterleukin 6 (IL6) is both a pleiotropic cytokine and an immune-related gene. Interleukin 6 receptor (IL6R) is the receptor for IL6. It may be closely connected to the development of lung cancer. This research aims to explore the prognostic value of IL6R and prevent overtreatment of patients with lung adenocarcinoma (LUAD).MethodsIn this study, the expression of IL6R in tumor tissues and surrounding tissues was first analyzed by immunohistochemistry in the Affiliated Hospital of Nantong University (NTU) cohort. Secondly, we downloaded information from The Cancer Genome Atlas (TCGA) for the TCGA cohort and used this information to explore the messenger RNA (mRNA) level of IL6R. We then used Kaplan-Meier survival analyses, univariate and multivariate Cox analyses, nomogram models, and decision curve analyses to assess the prognostic value of IL6R. In addition, we also analyzed immune cell infiltration and the signaling pathways related to IL6R through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).ResultsThrough the data analysis of the NTU cohort and the TCGA cohort, it was found that the expression of IL6R in normal tissues around the tumor was higher than that in tumor tissue, and was positively correlated with the overall survival (OS) of LUAD patients. Additionally, low expression of IL6R was found to be an independent predictor of poor prognosis among the patients in these two research cohorts. Next, using GO, KEGG, and GSEA analyses, we found that partially infiltrated tumor immune cells might be related to earlier staging and better prognosis of patients with LUAD. Finally, the study of the 3-5-year survival rate of LUAD patients through the nomogram showed that the expression of IL6R could improve the accuracy of prediction to prevent the overtreatment of some LUAD patients.ConclusionsIn summary, our study indicated that the low expression of IL6R was associated with poor prognosis among LUAD patients and that low expression of IL6R is a potential independent risk factor that could provide a basis for strengthening postoperative classification management of such patients.

Dataset Information

Correlation between oncogene integrator complex subunit 7 and a poor prognosis in lung adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

Correlation between oncogene integrator complex subunit 7 and a poor prognosis in lung adenocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets