scholarly journals Differential Expression of the Androgen Receptor, Splice Variants and Relaxin 2 in Renal Cancer

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 731
Author(s):  
Joanna Bialek ◽  
Maria Piwonka ◽  
Felix Kawan ◽  
Paolo Fornara ◽  
Gerit Theil
Keyword(s):  
Androgen Receptor ◽  
Renal Cancer ◽  
Clear Cell ◽  
Splice Variants ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Cytokine Levels ◽  
Relaxin 2 ◽  
Matched Samples

Background: The role of the androgen receptor (AR) in renal cell carcinoma (RCC) is unclear. We aimed to analyze the expression of AR and its splice variants (SVs) and their correlation with relaxin 2 (RLN2) and cytokines in RCC. Methods: We investigated the expression of RLN2 and AR variants in 25 clear cell RCC (ccRCC) and 9 papillary (pRCC) tumor tissues and the corresponding controls using quantitative PCR and serum RLN2, testosterone and cytokine levels in matched samples using ELISA and chemiluminescent immunometric assay, respectively. Results: ccRCC tissues but not pRCC tissues more frequently expressed AR and the SVs than did normal tissues. All pRCC samples expressed more AR than did ccRCC samples. The highest expression of all AR variants except AR-V12 was found in low-stage tumors, with dominant expression of AR-V7. In males in the ccRCC cohort, the expression of AR-FL, AR-V1 and AR-V3 was significantly correlated with that of RLN2. The secretion pattern of proinflammatory IL-6 was higher in ccRCC than in pRCC. Conclusions: The results highlight additional molecular differences between ccRCC and pRCC, suggesting the influence of external factors on the whole kidney or genetic predispositions to developing certain types of renal cancer, and may support further pathological analysis and studies of targeted hormone therapy.

scholarly journals The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3425
Author(s):  
Zigui Chen ◽  
Po Yee Wong ◽  
Cherrie W. K. Ng ◽  
Linlin Lan ◽  
Sherwood Fung ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Early Detection ◽  
Patient Outcomes ◽  
Host Gene ◽  
Oral Microbiota ◽  
Gene Methylation ◽  
Normal Tissues ◽  
Oral Rinse ◽  
Tumor Tissues

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host–microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.

scholarly journals Expression Patterns and Prognostic Values of ORMDL1 in Different Cancers

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Tengjiao Zhu ◽  
Yingtong Chen ◽  
Shuyuan Min ◽  
Fang Li ◽  
Yun Tian
Keyword(s):  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Sphingolipid Metabolism ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Important Regulator ◽  
Coexpressed Genes

The mammalian orosomucoid-like gene family (ORMDL), containing ORMDL1, ORMDL2, and ORMDL3, is the important regulator of sphingolipid metabolism, which is relevant to cell growth, proliferation, migration, and invasion. Since the role of ORMDL1 in cancers remained unclear, the main purpose of our study was to explore the expression patterns and prognostic values of ORMDL1 in different tumors, especially in cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B cell lymphoma (DLBCL), acute myeloid leukemia (LAML), and thymoma (THYM). Bioinformatics tools including GEPIA, CCLE, LinkedOmics, cBioPortal, and TIMER databases were used. As a result, the expression levels of ORMDL1 in tumor tissues and normal tissues varied in different cancers, especially significantly upregulated in CHOL, DLBCL, LAML, and THYM. Moreover, ORMDL1 mRNA was also highly expressed in cell lines of DLBCL and LAML. Further studies showed that ORMDL1 overexpression was associated with poor prognosis in DLBCL, but not significant in CHOL, LAML, and THYM. Consistently, there were genetic alterations of ORMDL1 in DLBCL, and patients with genetic alterations indicated worse survival. Coexpressed genes and related biological events with ORMDL1 in DLBCL were found via LinkedOmics, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between ORMDL1 and cancer immune cells was investigated, and ORMDL1 expression was positively correlated with infiltrating levels of B cells. In conclusion, ORMDL1 is suggested to be a tumorigenic factor and considered as the potential therapeutic target and prognostic biomarker in DLBCL.

Pathological significance of C3aR signaling in the tumor cells of clear cell renal cell carcinoma: a clinical observation

2020 ◽  
Author(s):  
Jing-Min Zheng ◽  
Xiong Tian ◽  
Mei-Fu Gan ◽  
Hong-Yuan Yu ◽  
Li-Cai Mo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Tumor Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Ki 67 ◽  
Tumor Tissues

Abstract Background Increasing evidences suggest that anaphylotoxin-induced signaling is involved in tumor pathogenesis, but the exact role of C3a/C3aR signaling in clear cell renal cell carcinoma (ccRCC) still remains to be investigated. The aim of the study was to investigate the pathological significance of C3a/C3aR signaling in ccRCC. Methods The expression of C3aR and C3 mRNA in the tumor tissues of ccRCC patients were analyzed by using the data from TCGA database. The expression of C3aR and C3c protein in the tumor tissues of another 129 ccRCC patients were examined by immunohistochemistry. Results Compared with the normal controls, both C3aR and C3 mRNA increased in the tumor tissues. Patients with higher C3 mRNA had shorter survival time. Immunostaining for C3aR and C3c also increased in the tumor tissues when compared with the adjacent normal renal tissues. Higher level of C3aR in the tumor cells and C3c in the tumor tissues were found to be associated with indices reflecting poor prognosis including higher tumor grade, the presence of necrosis in tumor tissues and shorter survival time. Besides, the level of C3aR in the tumor cells and C3c in the tumor tissues were found to correlate with the level of Vimentin, E-Cadherin and the ratio of Ki-67 positive tumor cells. Conclusions These results support the idea that C3aR signaling is over-activated in the tumor cells and may contribute to the progression of ccRCC. Inducing EMT and promoting the proliferation of tumor cells might be among the mechanisms underlying the role of C3aR signaling in ccRCC.

scholarly journals A positive role of c-Myc in regulating androgen receptor and its splice variants in prostate cancer

Oncogene ◽  
2019 ◽  
Vol 38 (25) ◽  
pp. 4977-4989 ◽  
Author(s):  
Shanshan Bai ◽  
Subing Cao ◽  
Lianjin Jin ◽  
Margaret Kobelski ◽  
Blake Schouest ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Splice Variants ◽  
Positive Role

scholarly journals Pseudogene HSPA7 is a Poor Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) and Correlated With Immune Infiltrates

2021 ◽  
Author(s):  
Chunjin Ding ◽  
Rundong He ◽  
Jinghan Zhang ◽  
Zhan Dong ◽  
Jun Wu
Keyword(s):  
Cox Regression ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Renal Clear Cell Carcinoma ◽  
Database Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Infiltrating Cells ◽  
Cox Analysis

Abstract Background: Pseudogenes played important roles in tumorigenesis, while there are nearly no reports about the expression and roles of HSPA7 in the cancer. Methods: Firstly,we used Logistic regression,the KS test, the GEPIA database, UALCAN database and qRT-PCR to analyze the level of HSPA7 expressed in KIRC,then we used the Cox regression and the Kaplan-Meier curve to analyze the overall survival(OS) of KIRC patients with different Clinico-pathological parameters. Thirdly, we used the multivariate Cox analysis of influencing factors to compare the correlation between the HSPA7 expression level and the clinical parameters. Finally, we used multi-GSEA analysis and the Tumor Immunoassay Resource (TIMER) database to explore the functional role of HSPA7 in KIRC. Results: The HSPA7 is highly expressed in KIRC tumor tissues, and its expression is related to clinico-pathological features and survival in KIRCpatints.GSEA analysis displayed the high expression of HSPA7 in KIRC were related to several tumor-related and immune-related pathways. With the TIMER database analysis we showed that HSPA7 levels were correlated with the CD4+ T cells, neutrophils and Dendritic Cell.Conclusions: Our study showed that HSPA7 is very important in the tumor progression and may act as a poor prognostic biomarker for KIRC tumor by modulating immune infiltrating cells.

scholarly journals Identification of the Role of GLS2 in the Development and Progression of Clear Cell Renal Cell Carcinoma.

2020 ◽  
Author(s):  
dantong sun ◽  
lu tian ◽  
yang wo ◽  
han zhao ◽  
weihua yan ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clear Cell ◽  
Intratumor Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Tumor Tissues ◽  
Basic Characteristics ◽  
Geo Database

Abstract Background The incidence of RCC has drastically increased in recent years. The large intratumor heterogeneity of RCC, especially ccRCC, usually leads to treatment failure. In addition, single biomarkers have a limited ability to predict prognosis. Therefore, we performed this study to select variables and provided a simple but efficient way to predict prognosis.MethodThree studies from GEO database were involved in the DEGs selection. A total of 840 RCC patients and 524 ccRCC patients from TCGA database were involved in the prognostic analyses. Nomograms based on Cox regression model were used to select variables to predict the prognosis, and GSEA was used to demonstrate the potential pathways altered by gene expression.ResultOur study suggested that DEGs existed between metastatic and primary tumor tissues. Loss of GLS2 was related to poor prognosis in RCC and ccRCC. These results revealed that GLS2 expression, combined with basic characteristics, including age and TNM stage, could efficiently predict prognosis. GLS2 serves as a tumor suppressor in ccRCC, loss of GLS2 function endows cells with oncogenic functions and is related to advanced disease. According to the GSEA results, loss of GLS2 function may alter the cell cycle by activating the E2F pathway.ConclusionGLS2 is a tumor suppressor in RCC. Loss of GLS2 function in ccRCC predicts a poor prognosis via the underlying E2F pathway. Nomograms based on DEGs and clinical features provide physicians with a simple but efficient way to predict prognosis. Further studies are needed to verify the pathway in our study.

scholarly journals Genome-wide transcriptome and translatome analyses reveal the role of protein extension and domestication in liver cancer oncogenesis

2021 ◽  
Author(s):  
Nima Wang ◽  
Dalei Wang
Keyword(s):  
Natural Selection ◽  
Liver Cancer ◽  
Stop Codon ◽  
Protein Sequences ◽  
Normal Tissues ◽  
Genome Wide ◽  
Cancer Field ◽  
Tumor Tissues ◽  
Translation Signals

ABSTRACTOne gene could be transcribed to different RNA isoforms, and then produce various forms of protein sequences. This mechanism largely diversifies the cellular pool and allows natural selection to select from a wider range of substrates. Most of the deleterious changes should be either purged or only be observed in patients with deficiencies or diseases. In the cancer field, the “intra-gene” changes between tumor and normal tissues such as the alternative splicing, stop codon read-through, or protein domestication could not be captured by differential expression analyses. In this work, we collected public transcriptome and translatome data from ten patients with liver cancer, and performed genome-wide comparison on the stop codon read-through and protein domestication events. Both events could diversify the proteome without changing the genome sequence. Surprisingly, we found that compared to normal tissues, the tumor tissues globally have significantly higher occurrence of stop codon read-through events. Similarly, the translation signals of non-coding repetitive elements (protein domestication) are elevated in tumor samples. These read-through and domestication events show limited overlapping across the ten patients, suggesting the randomness of the occurrence. It also indicates that these tumor-specific read-through and domestication events should be deleterious, and should be purged by natural selection if they are not collected timely. Our work manifests the role of protein extension and domestication in liver cancer oncogenesis, and adds new aspects to the cancer field.

scholarly journals Fibroblast Growth Factor 11 (FGF11) Promotes Non-small Cell Lung Cancer (NSCLC) Progression by Regulating Hypoxia Signaling Pathway

2021 ◽  
Author(s):  
Xiaowei Wu ◽  
Minjie Li ◽  
Yu Deng ◽  
Shun Ke ◽  
Fan Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Hypoxia Signaling

Abstract Background: Recently, accumulating studies highlight the critical regulatory roles of fibroblast growth factors (FGF), and a series of FGF, participated in the progression of multiple human cancers, including non-small cell lung cancer (NSCLC). Methods: Gene transcriptome analysis was used to identify the differential expression of FGF11 in NSCLC tumor tissues, GSE75037 and GSE81089 database analysis was performed on NSCLC tumor tissues and adjacent normal tissues to validate the expression of FGF11. Then, we selected 100 cases of NSCLC tumor tissues and 30 cases of matched adjacent normal tissues to confirm the mRNA and protein level of FGF11 by qRT-PCR and immunohistochemistry. Bioinformatics analysis and dual luciferase reporter analysis was also performed to examine the direct regulatory of FGF11 by miR-525-5p. CCK-8 and transwell assay was also performed to detect the cell proliferation, migration and invasion. Signal pathway analysis was also investigated the effect of FGF11 on NSCLC cell proliferation was associated with the hypoxia signaling pathway. The role of FGF11 in NSCLC tumor growth was further explored by in vivo study.Results: FGF11 was overexpressed in NSCLC tumor tissues and tumor cell lines, the high expression of FGF11 was closely associated with poor overall survival of NSCLC patients. In vitro loss- and gain- of function experiments demonstrated that FGF11 knockdown inhibited, whereas FGF11 overexpression promoted the proliferation, migration and invasion of NSCLC cells. The dual luciferase reporter assay confirmed that FGF11 was downregulated by miR-525-5p, and the effect of FGF11 on cell proliferation, migration and invasion could be interfered by miR-525-5p. We further found that FGF11 had significant correlation with hypoxia signaling pathway activation, meanwhile regulating HIF-1α. Further experiments implicated that the oncogenic role of FGF11 could be blocked via interfering of HIF-1α in NSCLC cells. Moreover, knockdown of FGF11 suppressed NSCLC tumor growth whereas overexpression of FGF11 promoted tumor growth in vivo. Conclusions: FGF11 might be functioned as an oncogene in tumor development, the findings of our study revealed a novel regulatory mechanism of FGF11 involved in hypoxia signaling pathway, which offers novel strategies for the treatment of NSCLC.

scholarly journals Epulis-Like Presentation of Gingival Renal Cancer Metastasis

2017 ◽  
Vol 10 (2) ◽  
pp. 758-763 ◽  
Author(s):  
Gianfilippo Nifosì ◽  
Hubert Bressand ◽  
Antonio Fabrizio Nifosì ◽  
Lorenzo Nifosì ◽  
Pierre Damseaux
Keyword(s):  
Renal Cancer ◽  
Cancer Metastasis ◽  
Soft Tissues ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Common Site ◽  
Primary Tumors ◽  
Immunohistochemical Techniques ◽  
Renal Origin

Mouth metastatic cancers are very rare and they usually represent the evidence of a widespread disease. Common primary tumors are lung carcinoma in men and breast carcinoma in women, followed by kidney cancer. In the oral soft tissues, the gingiva is the most common site, suggesting a possible role of inflammation in the attraction of circulating tumor cells. Oral metastasis has a serious prognosis. In this work, we describe the case of a 58-year-old man affected by renal cancer, who was brought to our attention for the appearance of a gingival swelling. Initially, the lesion was excised through a provisional clinical diagnosis of epulis. Subsequently, anatomopathological analysis showed a metastasis compatible with clear-cell carcinoma and specifically its renal origin was confirmed by immunohistochemical techniques.

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