High CTSL2 expression predicts poor prognosis in patients with lung adenocarcinoma.
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ABSTRACT:
SUBMITTER: Song J
PROVIDER: S-EPMC8507295 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Keratin 8 (KRT8), a type II basic intermediate filament (IF) protein, is essential for the development and metastasis of various cancers. In this study, by analyzing RNA-seq data from the Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), we have determined the expression profile of KRT8, and assessed its prognostic significance and the possible mechanism underlying the dysregulation. Our results showed that KRT8 mRNA expression was significantly up-regulated in both LUAD and LUSC tissues compared with normal lung tissues. The high KRT8 expression group for LUAD patients significantly reduced overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate analysis revealed that KRT8 expression was an independent prognostic indicator for poor OS and RFS in LUAD patients. However, KRT8 expression had no prognostic value in terms of OS and RFS for LUSC. By exploring DNA copy number alterations (CNAs) of the KRT8 gene in LUAD, we found that DNA low copy gain (+1 and +2) was associated with elevated KRT8 mRNA expression. From the above findings, we have deduced that KRT8 is aberrantly expressed in LUAD tissues and that its expression might independently predict poor OS and RFS for LUAD patients, but not for LUSC patients.
| S-EPMC6360019 | biostudies-literature
Project description:IntroductionLung adenocarcinoma (LUAD) is the most common type of lung cancer. DEP domain-containing 1 B (DEPDC1B) is involved in the development of several cancers; however, its role in LUAD is unknown. Therefore, we aimed to determine the biological function and prognostic value of DEPDC1B in LUAD.Material and methodsWe analyzed the correlation between DEPDC1B expression and the clinical features of LUAD and lung squamous cell carcinoma (LUSC). Survival was evaluated by generating Kaplan-Meier curves, which were used to analyze the relationship between DEPDC1B expression and prognosis in LUAD and LUSC. DEPDC1B expression in tumor and normal tissues from patients with LUAD and LUSC was determined using immunohistochemistry, and its clinical significance was analyzed. Finally, the correlation between the expression and biological function of DEPDC1B in LUAD was examined.ResultsOur findings revealed that DEPDC1B expression was higher in tumor tissues than that in normal tissues from patients with LUAD and LUSC (P < 0.001). These results were confirmed in clinical samples from patients using immunohistochemistry. Analysis of a dataset from The Cancer Genome Atlas (TCGA) showed that high DEPDC1B expression was associated with poor prognosis only in patients with LUAD (P < 0.001). Similarly, high DEPDC1B expression was related to shorter overall survival (OS) and progression-free interval (PFI) in patients with LUAD. These associations were not observed in LUSC. Functional enrichment analysis suggested that DEPDC1B promoted tumor development in LUAD by regulating the cell cycle.ConclusionHigh DEPDC1B expression predicts poor prognosis in patients with LUAD. Thus, DEPDC1B has potential as a therapeutic target for LUAD.
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Project description:Monocarboxylate transporter 4 (MCT-4) serves a key function in transporting lactate across the plasma membrane in various types of human cancer. Evidence indicates that MCT-4 expression is associated with non-small cell lung cancer; however, the distribution and clinical significance of MCT-4 in the lung adenocarcinoma (AC) subtype remain unknown. Thus, the aim of the present study was to explore the clinicopathological significance and prognostic values of MCT-4 expression in lung AC. Quantum dots-based immunofluorescence histochemistry was performed to observe the expression of MCT-4 in 146 specimens of lung AC and corresponding normal lung tissues. MCT-4 protein and mRNA were detected by western blotting and reverse transcription-quantitative polymerase chain reaction from 30 fresh samples of lung AC and corresponding normal lung tissues. Of the 146 samples, 25 (17.1%) exhibited high and 121 (82.9%) exhibited low MCT-4 expression. MCT-4, at the protein and mRNA level, was significantly increased in tumor specimens compared with corresponding normal lung tissue (P<0.05). MCT-4 protein expression was significantly associated with depth of invasion (P=0.034). A survival curve analysis indicated that high MCT-4 expression in lung AC was associated with a decreased overall survival rate (P=0.001). Multivariate analysis demonstrated that high MCT-4 level was an independent prognostic factor (hazard ratio, 3.192; 95% confidence interval, 1.804-5.646; P=0.001) for patients with lung AC. The results have demonstrated that high MCT-4 expression is significantly associated with the poor prognosis and disease progression of patients with lung AC. Therefore, MCT-4 may be a candidate therapeutic target in lung AC.
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Project description:Interleukin-enhancer binding factor 3 (ILF3) is a double-stranded RNA-binding protein that has been reported to contribute to the occurrence and progression of various malignant tumors. The aim of the present study was to evaluate the prognostic value of ILF3 and to apply this knowledge to avoid excessive medical treatment in patients with lung adenocarcinoma (LUAD). ILF3 expression in a discovery set consisting of tumor and peri-tumor tissue microarrays was analyzed using immunohistochemical methods. The mRNA level of ILF3 was subsequently analyzed in a validation set downloaded from The Cancer Genome Atlas. The Kaplan-Meier method, univariate and multivariate Cox analyses, decision curve analysis and nomogram models were used to evaluate the prognostic value of ILF3. ILF3 expression was upregulated in tumor tissues compared with peri-tumor tissues and was negatively associated with the overall survival time of patients with LUAD in the discovery and validation sets. Moreover, ILF3 expression was used for risk stratification in patients with tumor-node-metastasis stages II-IV and poor-to-moderate tumor differentiation. ILF3 expression was identified as an independent predictor of adverse prognosis for patients with LUAD in the discovery and validation sets. Finally, nomogram models for the 3- and 5 year survival time of patients with LUAD revealed that ILF3 expression may be used to improve the predictive accuracy of the prognosis and to avoid excessive medical treatment for certain patients with the disease. Overall, the data obtained in the current study revealed that high ILF3 expression was associated with poor prognosis, and demonstrated that ILF3, as a potential independent risk factor, may improve the hierarchical postoperative management of patients with LUAD.
| S-EPMC7039148 | biostudies-literature
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.
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Project description:Eukaryotic initiation factor 3 subunit M (EIF3M) is required for key steps in the initiation of protein synthesis, and dysregulation of EIF3M is associated with tumorigenesis. This study aimed to explore the clinicopathological and prognostic role of EIF3M in patients with colon adenocarcinoma. A total of 82 pathology specimens, 20 freeze-thawed tumors and 80 healthy controls were used to investigate the expression of EIF3M in colon adenocarcinoma through immunohistochemistry, western blotting, RT-qPCR and ELISA. In addition, Kaplan-Meier curves and Cox regression analysis were used to analyze overall survival (OS) and disease-free survival (DFS). Furthermore, the Oncomine database was used for analyzing EIF3M expression. The positive rate of EIF3M in colon adenocarcinoma was higher compared with that in normal colon tissues (62.20% vs. 29.27%; P<0.001). The mean score of EIF3M was also higher in colon adenocarcinoma compared with normal colon tissue (17.28±10.05 vs. 6.53±4.87; P<0.001). The levels of EIF3M expression in freeze-thawed tumors and serum from 20 patients with colon adenocarcinoma were higher than those in normal tissues and serum from healthy controls, respectively (P<0.001). In addition, positive expression of EIF3M was associated with tumor size (P=0.002) and Dukes' stage (P<0.001). In multivariate Cox regression analysis, EIF3M expression was an independent prognostic factor for OS (P=0.003) and DFS (P=0.001). Oncomine database analysis showed a higher expression of EIF3M expression in colon adenocarcinoma compared with normal colon tissues, colon squamous cell carcinomas or gastrointestinal stromal tumors. In conclusion, EIF3M expression was associated with tumor size and Dukes' stage in colon adenocarcinoma. Hence, EIF3M is a potential prognostic indicator for colon adenocarcinoma.
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Project description:Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. The JAK/STAT signaling pathway is involved in pancreatic cancer tumorigenesis. However, the prognostic value of JAK2 expression in resectable PDAC is unclear. Method In this study, we performed a clinicopathological analysis of 62 resectable PDAC cases with a primary focus on survival. JAK2 expression was examined by immunohistochemistry. The relationship between JAK2 expression and clinicopathological features and prognosis was analyzed. Results Survival curve analyses revealed that high levels of JAK2 expression predict a poor prognosis in resectable PDAC patients. Multivariate analysis confirmed that JAK2 expression can predict the prognosis of PDAC. Conclusions Assessment of JAK2 protein expression may be a promising method to predict prognosis in patients with resectable PDAC.
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Project description:Protein kinase D2 (PKD2) has been reported to be related with progression and invasion in various cancers. However, its prognostic value and the underlying mechanism in lung cancer remains unclear. Herein we evaluated the expression of PKD2 in lung adenocarcinoma and investigated its relationship with EMT. GSEA, TCGA and K-M plotter database were applied and revealed that high PKD2 expression predicted poor outcome and related with lymph nodes metastasis in lung cancer. IHC and qRT-PCR were performed and found PKD2 was elevated in lung adenocarcinoma and negatively related with OS (p?=?0.015), PFS (p?=?0.006) and the level of E-cadherin (p?=?0.021). Experiment in lung adenocarcinoma cell lines demonstrated up-regulation of PKD2 led to high expression of mesenchymal markers (N-cadherin, vim, mmp9 et al.) and EMT transcription factors(zeb1, twist, snail), and the results were reversed when PKD2 was knocked down. Further investigation showed that abrogation of PKD2 inhibited A549 cell migration, invasion, proliferation and induced cell arrest in G2/M phase. We concluded that high expression of PKD2 was associated with poor prognosis and cancer progression in lung adenocarcinoma patients by promoting EMT.
| S-EPMC6362154 | biostudies-literature
Project description:Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN/APLNR system was involved in a variety of pathological and physiological functions, such as tumorigenesis and development. However, its prognostic roles in patients with central nervous system (CNS) cancers remain unknown. The present study was designed to explore the expression profile, prognostic significance, and interaction network of APLN/APLNR by integrating data from Oncomine, GEPIA, LOGpc, STRING, GeneMANIA, and immunohistochemical staining. The results demonstrated that APLN and APLNR mRNA expression were significantly increased in CNS cancers, including both low-grade glioma (LGG) and glioblastoma (GBM), when compared with normal CNS tissues. The high APLN, but not APLNR, expression was significantly correlated with overall survival (OS), recurrence free survival (RFS), and progression free survival (PFS) of LGG patients. However, neither APLN nor APLNR expression was significantly related to prognostic value in terms of OS, disease free interval (DFI), disease specific survival (DSS), or progression free interval (PFI) for GBM patients. Additionally, immunohistochemistry staining confirmed the increased APLN expression in tissues of LGG patients with grade II than grade I. These results showed that an elevated APLN level could predict poor OS, RFS, and PFS for LGG patients, and it could be a promising prognostic biomarker for LGG.
| S-EPMC9526648 | biostudies-literature
Project description:BackgroundPyruvate kinase M2 (PKM2) is critical regulator contributing to Warburg effect. However, the expression pattern and prognostic value of PKM2 remain unknown in lung adenocarcinoma (LUAD). The aim of this study is to clarify the prognostic value of PKM2 via intergrated bioinformatics analysis.MethodsFirstly, mRNA expression levels of PKM2 in LUAD were systematically analyzed using the ONCOMINE and TCGA databases. Then, the association between PKM2 expression and clinical parameters was investigated by UALCAN. The Kaplan-Meier Plotter was used to assess the prognostic significance of PKM2. Finally, the relationship between PKM2 expression and its genetic and epigenetic changes was evaluated with MEXPRESS and MethHC database.ResultsPooled analysis showed that PKM2 is frequently upregulated expression in LUAD. Subsequently, PKM2 expression was identified to be positively associated with tumor stage and lymph node metastasis and also strongly correlated with worse OS (P = 2.80e-14), PPS (P = 0.022), FP (P = 1.30e-6) and RFS (P = 3.41e-8). Importantly, our results demonstrated that over-expressed PKM2 is associated with PKM2 hypomethylation and copy number variations (CNVs).ConclusionThis study confirms that over-expressed PKM2 in LUAD is associated with poor prognosis, suggesting that PKM2 might act as a promising prognostic biomarker and novel therapeutic target for LUAD.
| S-EPMC7036274 | biostudies-literature