Elevated expression of ASF1B correlates with poor prognosis in human lung adenocarcinoma

2021 ◽  
Vol 18 (2) ◽  
pp. 115-127
Author(s):  
Zhenxing Feng ◽  
Jiao Zhang ◽  
Yafang Zheng ◽  
Qingzhang Wang ◽  
Xiaochuan Min ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Tumor Development ◽  
Tumor Stage ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Advanced Tumor Stage ◽  
Aberrant Expression ◽  
Free Survival ◽  
Advanced Tumor

Aim: ASF1 is involved in tumorigenesis. However, its possible role in lung adenocarcinoma (LUAD) is unclear. This study thus explored the role of ASF1A and ASF1B in LUAD. Materials & methods: Data from The Cancer Genome Atlas and Gene Expression Omnibus were employed to investigate ASF1A and ASF1B expression and its roles in LUAD prognosis. Immunohistochemistry was applied to determine the protein expression of ASF1B of 30 LUAD patients. Results: The upregulation of ASF1B in tumor tissues is associated with worse overall survival and progress-free survival and is correlated with advanced tumor stage and tumor development. However, aberrant expression of ASF1A was not found in LUAD and ASF1A was not related to patients’ overall survival and progress-free survival. Conclusion: ASF1B could be a promising prognostic and therapeutic biomarker in LUAD.

scholarly journals Increased GOLM1 Expression Independently Predicts Unfavorable Overall Survival and Recurrence-Free Survival in Lung Adenocarcinoma

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481877800 ◽  
Author(s):  
Xi Liu ◽  
Lei Chen ◽  
Tao Zhang
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Methylation Status ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Recurrence Free Survival ◽  
Free Survival

Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years’ survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (−1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = −0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.

scholarly journals Overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues predicts poor survival in pancreatic ductal adenocarcinoma

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Shu Dong ◽  
Fei Huang ◽  
Hao Zhang ◽  
Qiwen Chen
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Gene Expression Omnibus ◽  
Ductal Adenocarcinoma ◽  
Advanced Tumor Stage ◽  
Kaplan Meier ◽  
Advanced Tumor ◽  
Tumor Tissues

AbstractOverexpressed genes in tumors usually contributed to aggressiveness in pancreatic ductal adenocarcinoma (PDAC). Using Gene Expression Omnibus (GEO) profiles including GSE46234, GSE71989, and GSE107610, we detected overexpressed genes in tumors with R program, which were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO), and Reactome pathway databases. Then, we performed a survival analysis of enriched genes based on TCGA profile. Our results revealed that high BUB1B, CCNA2, CDC20, and CDK1 expression in tumors was significantly associated with worse overall survival (OS) (Log rank P=0.00338, P=0.0447, P=0.00965, and P=0.00479, respectively), which was validated using a Kaplan–Meier plotter with a median cutoff (Log rank P=0.028, P=0.0035, P=0.039, and P=0.0033, respectively). Moreover, overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues was significantly associated with disease-free survival (DFS) in PDAC patients (Log rank P=0.00565, P=0.0357, P=0.00104, and P=0.00121, respectively). BUB1B, CCNA2, CDC20, and CDK1 were significantly overexpressed in deceased PDAC patients (all P<0.01) and in patients with recurrence/disease progression (all P<0.05). In addition, PDAC patients with neoplasms of histologic grade G3-4 had significantly higher BUB1B, CCNA2 and CDC20 levels (all P<0.05). In conclusion, the up-regulation of BUB1B, CCNA2, CDC20, CDK1, and WEE1 in tumor tissues are associated with worse OS and DFS in PDAC and is correlated with advanced tumor stage and tumor development.

scholarly journals Functions and clinical significance of KLRG1 in the development of lung adenocarcinoma and immunotherapy

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaodong Yang ◽  
Yuexin Zheng ◽  
Zhihai Han ◽  
Xiliang Zhang
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Killer Cell ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Normal Lung ◽  
Using Data ◽  
Low Expression

Abstract Background As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 on the efficacy of immune-checkpoint inhibitor in the treatment of lung adenocarcinoma (LUAD), as well as contribute to the possible molecular mechanisms of KLRG1 on LUAD development. Methods Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We also established stable LUAD cell lines with KLRG1 gene knockdown and investigated the effect of KLRG1 knockdown on tumor cell proliferation. We further studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy. Results The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 and H1299 tumor cells. And low expression of these four factors was associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses to immunotherapy in LUAD patients. Conclusion Based on these findings, we inferred that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.

scholarly journals Expression of RNA-binding motif 10 is associated with advanced tumor stage and malignant behaviors of lung adenocarcinoma cancer cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769174 ◽  
Author(s):  
Guofang Guan ◽  
Ranwei Li ◽  
Wenfang Tang ◽  
Tiecheng Liu ◽  
Zhenzhong Su ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Messenger Rna ◽  
Rna Binding ◽  
Tumor Stage ◽  
Receptor Interaction ◽  
Binding Motif ◽  
Advanced Tumor Stage ◽  
Complementary Dna ◽  
Advanced Tumor ◽  
Lung Adenocarcinoma Cancer

This study assessed RNA-binding motif 10 expression in lung adenocarcinoma tissues and examined the role and mechanism of RNA-binding motif 10 in the regulation of lung adenocarcinoma malignancy. Lung adenocarcinoma and corresponding adjacent non-tumor lung tissues from 41 patients were subjected to reverse transcription-polymerase chain reaction and Western blot assessment to detect RNA-binding motif 10 expression. Recombinant lentivirus carrying RNA-binding motif 10 complementary DNA was used to infect lung adenocarcinoma cell lines, A549 and H1299 cells. Complementary DNA microarray was used to profile RNA-binding motif 10–regulated genes. Levels of RNA-binding motif 10 messenger RNA and protein were significantly lower in lung adenocarcinoma tissues than those in paired non-tumor tissues (p < 0.001). Reduced RNA-binding motif 10 expression was found to be associated with an advanced tumor stage. RNA-binding motif 10 overexpression inhibited viability and colony formation capacity of lung adenocarcinoma cell lines and induced cell-cycle arrest at G0/G1 phase in A549 cells and at S phase in H1299 cells. Complementary DNA microarray analysis identified 304 upregulated and 386 downregulated genes induced by RNA-binding motif 10 overexpression, which may be involved in cancer, focal adhesion, peroxisome proliferator-activated receptor–regulated gene pathway, cytokine–cytokine receptor interaction, mitogen-activated protein kinase signaling, complement and coagulation cascades, platelet amyloid precursor protein pathway, extracellular matrix-receptor interaction, and small cell lung cancer–related genes. Expression of FGF2, EGFR, WNT5A, NF-κB, and RAP1A was downregulated, whereas expression of AKT2, BIRC3, and JUN was upregulated. RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif 10 regulates many gene pathways involving in the tumor development or progression.

scholarly journals Functions and Clinical Significance of KLRG1 in the Development of Lung Adenocarcinoma and Immunotherapy

2020 ◽  
Author(s):  
Xiaodong Yang ◽  
Yuexin Zheng ◽  
Zhihai Han ◽  
xiliang zhang
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Killer Cell ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Prognostic Biomarkers ◽  
Normal Lung ◽  
Using Data ◽  
Low Expression

Abstract Background. As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 in lung adenocarcinoma (LUAD) after immune-checkpoint inhibitor therapy, as well as to explore the role of a possible KLRG1 molecular mechanism on LUAD development.Methods. Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We further established a stable LUAD cell line with KLRG1 knockdown and investigate the effect of KLRG1 knockdown on tumor cell proliferation. We also studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy.Results. The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 tumor cells. And low expression of these four factors was all associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses in LUAD patients after immunotherapy.Conclusion. Based on these findings, we infer that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD. Key pointsKLRG1 inhibits the progress of LUAD.KLRG1 had significant correlation with immunotherapy response.KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.

scholarly journals PDZ Binding Kinase/T-LAK Cell-Derived Protein Kinase Plays an Oncogenic Role and Promotes Immune Escape in Human Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Tingting Feng ◽  
Yan Zhang ◽  
Sunbin Ling ◽  
Chenyang Xu ◽  
Yingqi Lyu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Solid Tumors ◽  
Immune Cell ◽  
Immune Escape ◽  
Tumor Stage ◽  
The Cancer Genome Atlas ◽  
Advanced Tumor Stage ◽  
Mitotic Kinase ◽  
Lak Cell ◽  
Advanced Tumor

Background. PDZ binding kinase (PBK)/T-LAK cell-derived protein kinase (TOPK) is an important mitotic kinase that promotes tumor progression in some cancers. However, the pan-cancer analysis of PBK/TOPK and its role in tumor immunity are limited. Methods. The oncogenic and immune roles of PBK in various cancers were explored using multiple databases, including Oncomine, Human Protein Atlas, ULCAN, Tumor Immune Estimation Resource 2.0, STRING, and Gene Expression Profiling Interactive Analysis 2, and data collected from The Cancer Genome Atlas and Genotype-Tissue Expression Project. Several bioinformatics tools and methods were used for quantitative analyses and panoramic descriptions, such as the DESeq2 and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Results. PBK was expressed at higher levels in most solid tumors than in normal tissues in multiple databases. PBK was associated with an advanced tumor stage and grade and a poor prognosis in most cases. PBK was associated with tumor immune cell infiltration in most cases and was especially positively correlated with TAMs, Tregs, MDSCs, and T cell exhaustion in KIRC, LGG, and LIHC. PBK was closely related to TMB, MSI, and immune checkpoint genes in various cancers, and patients with higher expression of PBK in KIRC, LGG, and LIHC had higher TIDE scores and lower immune responses in the predicted results. PBK was closely related to cell cycle regulation and immune-related processes in LIHC and LGG according to GO and KEGG enrichment analyses. Conclusions. PBK may play an oncogenic role in most solid tumors and promotes immune escape, especially in KIRC, LGG, and LIHC. This study suggests the potential value of PBK inhibitors combined with immunotherapy.

scholarly journals Analysis of the expression and potential molecular mechanism of interleukin-1 receptor antagonist (IL1RN) in papillary thyroid cancer via bioinformatics methods

2020 ◽  
Author(s):  
Zhenyu Xie ◽  
Xin Li ◽  
Yuzhen He ◽  
Song Wu ◽  
Shiyue Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Thyroid Cancer ◽  
Receptor Antagonist ◽  
Biological Function ◽  
Interleukin 1 ◽  
The Cancer Genome Atlas ◽  
Advanced Tumor Stage ◽  
Papillary Thyroid ◽  
Interleukin 1 Receptor Antagonist ◽  
Advanced Tumor

Abstract Background: Interleukin-1 receptor antagonist (IL1RN) has been reported as a biomarker of many cancers. However, the biological function of IL1RN in papillary thyroid carcinoma (PTC) remains undetermined. Methods: We obtained IL1RN expression data from The Cancer Genome Atlas (TCGA) database. Enrichment analysis of coexpressed genes and IL1RN methylation analysis were performed via LinkedOmics. The correlations between IL1RN and immune infiltrates were investigated via ESTIMATE, TIMER and TISIDB. We analyzed the association of IL1RN expression with pancancer overall survival (OS) via Gene Expression Profiling Interactive Analysis (GEPIA). Results: IL1RN showed higher expression levels and lower methylation levels in PTC tissues than in normal tissues. Higher IL1RN expression was significantly associated with shorter progression-free survival (PFS), advanced tumor stage, tumor metastasis, increased incidence of BRAF mutations, and decreased incidence of N-RAS and H-RAS mutations. Genes coexpressed with IL1RN participate primarily in immune-related pathways. IL1RN expression was positively correlated with immune infiltration, tumor progression and poor overall survival for all cancers. Conclusions: IL1RN is a good prognostic and diagnostic biomarker for PTC. IL1RN may promote thyroid cancer progression through immune-related pathways. Methylation may act as an upstream regulator of IL1RN expression and biological function. Additionally, IL1RN was shown to have broad prognostic value in a pancancer cohort.

scholarly journals HSD17B6 downregulation predicts poor prognosis and drives tumor progression via activating Akt signaling pathway in lung adenocarcinoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Tian Tian ◽  
Fu Hong ◽  
Zhiwen Wang ◽  
Jiaru Hu ◽  
Ni Chen ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Large Tumor ◽  
Mesenchymal Transition ◽  
Advanced Tumor

AbstractLung adenocarcinoma is one of the most frequent tumor subtypes, involving changes in a variety of oncogenes and tumor suppressor genes. Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6) could synthetize dihydrotestosterone, abnormal levels of which are associated with progression of multiple tumors. Previously, we showed that HSD17B6 inhibits malignant progression of hepatocellular carcinoma. However, the mechanisms underlying inhibiting tumor development by HSD17B6 are not clear. Moreover, its role in lung adenocarcinoma (LUAD) is yet unknown. Here, we investigated its expression profile and biological functions in LUAD. Analysis of data from the LUAD datasets of TCGA, CPTAC, Oncomine, and GEO revealed that HSD17B6 mRNA and protein expression was frequently lower in LUAD than in non-neoplastic lung tissues, and its low expression correlated significantly with advanced tumor stage, large tumor size, poor tumor differentiation, high tumor grade, smoking, and poor prognosis in LUAD. In addition, its expression was negatively regulated by miR-31-5p in LUAD. HSD17B6 suppressed LUAD cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and radioresistance. Furthermore, HSD17B6 overexpression in LUAD cell lines enhanced PTEN expression and inhibited AKT phosphorylation, inactivating downstream oncogenes like GSK3β, β-catenin, and Cyclin-D independent of dihydrotestosterone, revealing an underlying antitumor mechanism of HSD17B6 in LUAD. Our findings indicate that HSD17B6 may function as a tumor suppressor in LUAD and could be a promising prognostic indicator for LUAD patients, especially for those receiving radiotherapy.

Impact of tumor location on local recurrence after nephroureterectomy for upper tract urothelial carcinoma: Implications for adjuvant radiotherapy.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 390-390
Author(s):  
Sangjun Yoo ◽  
Dalsan You ◽  
In Gab Jeong ◽  
Cheryn Song ◽  
Bumsik Hong ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Lymphovascular Invasion ◽  
Tumor Stage ◽  
Tumor Location ◽  
Advanced Tumor Stage ◽  
High Grade ◽  
Pelvic Tumor ◽  
Free Survival ◽  
Advanced Tumor ◽  
Renal Pelvic Tumor

390 Background: To date, risk factors for local recurrence after complete removal of upper tract urothelial carcinoma (UTUC) have not been clearly identified. We evaluated the impact of tumor location on local recurrence in UTUC patients underwent radical nephroureterectomy. Methods: Among UTUC patients who underwent radical nephroureterectomy between 1998 and 2012, 192 (54.4%) patients with renal pelvic tumor and 161 (45.6%) patients with ureter tumor were included. Local recurrence was divided into regional lymph node recurrence (LNR) and surgical bed recurrence (SBR). The significance of tumor location and other variables on local recurrence were evaluated. Results: Lymphovascular invasion (p = 0.003), carcinoma in situ (p = 0.006) and high grade tumor (p < 0.001) were more common in ureter tumor. During median follow-up period of 73 months, local recurrence was occurred in 33 (9.3%) patients. Among subtype of local recurrence, SBR (8.1 vs. 2.1%, p = 0.011) were more common in patients with ureter tumor compared to renal pelvic tumor although the probability of regional LNR was not significantly different according to tumor location (7.5% vs. 3.1%, p = 0.088). 5-year local recurrence-free survival (80.5% vs. 94.2%, p = 0.002), LNR-free survival (89.8 vs. 96.5%, p = 0.046) and SBR-free survival (88.3% vs. 97.6%, p = 0.005) were inferior in ureter tumor compared to renal pelvic tumor. Ureter tumor (HR; 2.552, p = 0.017), high grade tumor (HR; 3.064, p = 0.016) and advanced tumor stage (≥T3) (HR; 3.236, p = 0.002) were associated with local recurrence. Ureter tumor (HR; 4.704, p = 0.002) and advanced tumor stage (HR; 4.840, p = 0.006) were risk factors for SBR. However, tumor location was not associated with LNR although lymphovascular invasion (HR; 5.451, p < 0.001) and high grade tumor (HR; 4.191, p = 0.012) were related with LNR. Conclusions: Ureter located tumor was associated with local recurrence which comes from the SBR. Adjuvant radiotherapy or surgical technique for reducing the risk of SBR should be considered in patients with ureter tumor.

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