Expression of Kruppel-like factor 8 and Ki67 in lung adenocarcinoma and prognosis.
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ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC5526062 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:Lung cancer is one of the most common causes of cancer-related death. In the past decade, the treatment and diagnosis of lung cancer have progressed significantly in early efforts to promote the survival of lung cancer patients. Kruppel like factor 16 (KLF16) is a zinc finger transcription factor that regulates a diverse array of developmental events and cellular processes. KLF16 is involved in the progression of various cancer types. However, the role of KLF16 in the development of lung cancer remains unknown. In this study, KLF16 was overexpressed in lung cancer samples. KLF16 downregulation inhibited lung cancer cell proliferation and migration. Conversely, KLF16 overexpression promoted lung cancer cell growth and invasion. Mechanistically, the expression level LMNB2 was suppressed by KLF16 knockdown and was promoted by KLF16 overexpression. The overall survival of patients with high LMNB2 levels was poor. Luciferase assays showed that KLF16 promoted the transcription activity of LMNB2 gene. Concomitantly, the expression level of LMNB2 was also higher in lung adenocarcinoma (LUAD) than in normal tissues, and its knockdown or overexpression can reverse the effect of KLF16 overexpression or knockdown on lung cancer cell proliferation, migration, and even tumorigenesis, indicating that LMNB2 also functions as an oncogene. In conclusion, KLF16 can be used as a potential therapeutic and preventive biomarker in lung cancer treatment and prognosis by actively regulating the expression of LMNB2.
| S-EPMC9161888 | biostudies-literature
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:Ribonucleotide reductase subunit M2 may play a role as a potential prognostic biomarker in several cancers. In this study, we evaluated whether RRM2 gene expression is associated with the prognosis of patients with lung adenocarcinoma (LUAD) using publicly available data from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and logistic regression were performed to evaluate the association between RRM2 expression and clinical features in patients with LUAD. Kaplan-Meier and Cox regression methods were used to examine the effect of RRM2 expression level in the overall survival, and a nomogram was performed to illustrate the correlation between the RRM2 gene expression and the risk of LUAD. TCGA data set was used for gene set enrichment analysis (GSEA). We also performed a further experiment in vitro to assess the effect of RRM2 expression on the proliferation and invasive abilities of LUAD cells and its key signaling pathway proteins. Our results revealed that the expression level of RRM2 in patients with LUAD was much higher than that in normal tissues (p = 3.99e-32). High expression of RRM2 was significantly associated with tumor stage (IV vs. I: OR = 3.02, p = 0.012) and TNM classification (T2 vs. T1: OR = 1.88, p = 0.001; N2 vs. N0: OR = 2.69, p < 0.001). Kaplan-Meier survival analysis showed that high expression of RRM2 was associated with a worse prognosis of LUAD compared low expression of RRM2 (p = 7.86e-04). Multivariate analysis showed that high RRM2 expression was an independent factor affecting overall survival (HR = 1.29, p < 0.001). The association between RRM2 gene expression and the risk of LUAD was presented in a nomogram. GSEA revealed that the cell cycle, p53 signaling pathway, DNA replication, small cell lung cancer, apoptosis, and pathways in cancer were differentially enriched in patients with high expression of RRM2. RRM2 over-expression promoted the proliferation and invasive abilities of LUAD cells. RRM2 over-expression increased the activation of Bcl-2 and E-cadherin signaling pathways, and reduced the activation of p53 signaling pathway. In summary, high RRM2 expression is an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.
| S-EPMC7906179 | 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:Background and objectiveKrüppel-like factor 8 (KLF8), a transcription factor, belongs to the KLF8 family. Currently, studies have shown that KLF8 is highly expressed in some tumors. However, the prognostic value and metastasis of KLF8 in cancers remain unclear. For the first time, we conducted meta-analysis to explore the relationship between KLF8 expression with prognosis and metastasis in various carcinomas patients.MethodsWeb of Science, PubMed, Embase, and Cochrane Library were systematically searched for eligible articles. Pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to evaluate the prognostic value and metastasis of KLF8 expression in human cancer patients.ResultsThe result revealed that highly expression level of KLF8 was significantly associated with poor overall survival (OS) (HR = 1.56, 95% CI: 1.26-1.87). Meanwhile, this significant correlation was also observed in subgroup analysis stratified by cancer types, source of HR, sample size, follow-up (months). In addition, highly expression of KLF8 was also closely associated with metastasis (HR = 1.37, 95% CI: 0.57-2.17) and tumor node metastasis stage (HR = 1.58, 95% CI: 0.90-2.25) in carcinomas.ConclusionIn summary, our meta-analysis indicates that overexpression of KLF8 may be associated with poor prognosis and higher incidence of metastasis in various carcinomas, and KLF8 may be used as a prognostic and metastatic indicator in human cancers.
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Project description:Cathepsin like 2 (CTSL2) is a lysosomal cysteine protease, and may be associated with tumor metastasis. However, CTSL2 has not been reported as a biomarker in lung adenocarcinoma (LUAD). In this study, bioinformatics analysis using data from The Cancer Genome Atlas was performed. Wilcoxon rank-sum test and chi-square test were carried out. Kaplan-Meier and Cox regression were performed to evaluate the effect of CTSL2 expression in the overall survival. Our results indicated that CTSL2 in tumor was significantly higher than that in normal tissue (P < 0.001). High CTSL2 expression was significantly associated with age (P = 0.02), vital status (P < 0.001), and T classification (P = 0.03), and correlated with poor overall survival (HR = 1.62, 95% CI = 1.21-2.18, P = 0.001). CTSL2 expression was an independent risk factor for overall survival in patients with LUAD (HR = 1.52, 95% CI = 1.12-2.05, P = 0.006). A nomogram was plotted for illustration of CTSL2 expression on the risk of LUAD. Furthermore, in vitro cell experiments showed the CTSL2 promoted the proliferation and migration of A549 cells. In summary, high CTSL2 expression predicts poor prognosis in patients with LUAD.
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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.
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Project description:A tumor can be viewed as a special "organ" that undergoes aberrant and poorly regulated organogenesis. Progress in cancer prognosis and therapy might be facilitated by re-examining distinctive processes that operate during normal development, to elucidate the intrinsic features of cancer that are significantly obscured by its heterogeneity. The global gene expression signatures of 44 human lung tissues at four development stages from Asian descent and 69 lung adenocarcinoma (ADC) tissue samples from ethnic Chinese patients were profiled using microarrays. All of the genes were classified into 27 distinct groups based on their expression patterns (named as PTN1 to PTN27) during the developmental process. In lung ADC, genes whose expression levels decreased steadily during lung development (genes in PTN1) generally had their expression reactivated, while those with uniformly increasing expression levels (genes in PTN27) had their expression suppressed. The genes in PTN1 contain many n-gene signatures that are of prognostic value for lung ADC. The prognostic relevance of a 12-gene demonstrator for patient survival was characterized in five cohorts of healthy and ADC patients [ADC_CICAMS (n = 69, p = 0.007), ADC_PNAS (n = 125, p = 0.0063), ADC_GSE13213 (n = 117, p = 0.0027), ADC_GSE8894 (n = 2, p = 0.01), and ADC_NCI (n = 282, p = 0.045)] and in four groups of stage I patients [ADC_CICAMS (n = 22, p = 0.017), ADC_PNAS (n = 76, p = 0.018), ADC_GSE13213 (n = 79, p = 0.02), and ADC_qPCR (n = 62, p = 0.006)]. In conclusion, by comparison of gene expression profiles during human lung developmental process and lung ADC progression, we revealed that the genes with a uniformly decreasing expression pattern during lung development are of enormous prognostic value for lung ADC.
| S-EPMC4139381 | biostudies-literature
Project description:BackgroundChemokines and chemokine receptors not only have significant roles in cancer metastasis and tumorigenesis but also act as antitumour agents. The interaction between the Crk-like adaptor protein (CrkL), which is encoded by the CRKL gene, and non-receptor tyrosine kinase c-ABL is reported to transform many cells into malignant cells. We examined the effects of CC chemokine receptor 7 (CCR7), CCR7 ligands and CrkL and c-ABL in lung adenocarcinoma.MethodsOne hundred and twenty patients with lung adenocarcinoma were included in this historical cohort analysis. We examined CCR7 and CCR7 ligands and CrkL and c-ABL mRNA expressions in surgically resected lung adenocarcinoma specimens and evaluated their contribution to prognosis, and the relationship with epidermal growth factor receptor (EGFR) and TP53 mutations.ResultsHigh CCR7 mRNA expressions indicated better prognoses than those of the groups with low CCR7 mRNA expressions (P=0.007, HR=2.00, 95% CI of ratio: 1.22 -3.31). In lung adenocarcinoma, CrkL and c-ABL mRNAs were related to CCR7 mRNA expression (P<0.0001). CrkL and c-ABL mRNA expressions were influenced by EGFR mutations. A high expression of CCL19 was a good prognostic factor of lung adenocarcinoma.ConclusionWe propose that CCR7 and CCL19 are clinically good prognostic factors and that CCR7 is strongly related to CrkL and c-ABL kinase mRNA expression in lung adenocarcinoma.
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Project description:Interleukin 34 (IL-34), an additional ligand of the colony-stimulating factor-1 receptor (CSF-1R), promotes the secretion of pro-inflammatory cytokines and stimulates NF-κB and JNK-related signaling pathways. However, the potential mechanism and prognostic value of IL-34 in lung adenocarcinoma (LUAD) remain obscure. In this study, IL-34 was found to be downregulated in LUAD tissues compared with para-carcinoma tissues, and loss of IL-34 expression was correlated with shorter overall survival (OS), which was validated by bioinformatics\ analysis in TCGA (The Cancer Genome Atlas) cohort and immunohistochemical analysis in the NTU (Nantong University) cohort, respectively. Subsequently, loss of IL-34 promotes negative regulation of the immune system and inhibits the infiltration of immune cells. Moreover, IL-34 deficiency was shown to be an independent adverse prognostic factor for patients with LUAD, and subgroup analysis indicated that IL-34 might contribute to the stratified management of patients with LUAD. IL-34-based nomogram model significantly improved the accuracy of prognostic predictions for OS of patients with LUAD, both in the TCGA cohort and the NTU cohort. Taken together, our data suggested that loss of IL-34 expression is associated with poor prognosis and negative regulation of the immune system of patients with LUAD, contributing to the stratified management of patients with LUAD.
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