scholarly journals Comprehensive Analysis of Expression, Clinicopathological Association and Potential Prognostic Significance of RABs in Pancreatic Cancer

2020 ◽  
Vol 21 (15) ◽  
pp. 5580 ◽  
Author(s):  
Shashi Anand ◽  
Mohammad Aslam Khan ◽  
Moh’d Khushman ◽  
Santanu Dasgupta ◽  
Seema Singh ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Small Gtpases ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Diabetic Patients ◽  
Rab Proteins ◽  
Clear Trend ◽  
Aberrant Expression ◽  
Transport Pathways ◽  
Altered Expression

RAB proteins (RABs) represent the largest subfamily of Ras-like small GTPases that regulate a wide variety of endosomal membrane transport pathways. Their aberrant expression has been demonstrated in various malignancies and implicated in pathogenesis. Using The Cancer Genome Atlas (TCGA) database, we analyzed the differential expression and clinicopathological association of RAB genes in pancreatic ductal adenocarcinoma (PDAC). Of the 62 RAB genes analyzed, five (RAB3A, RAB26, RAB25, RAB21, and RAB22A) exhibited statistically significant upregulation, while five (RAB6B, RAB8B, RABL2A, RABL2B, and RAB32) were downregulated in PDAC as compared to the normal pancreas. Racially disparate expression was also reported for RAB3A, RAB25, and RAB26. However, no clear trend of altered expression was observed with increasing stage and grade, age, and gender of the patients. PDAC from occasional drinkers had significantly higher expression of RAB21 compared to daily or weekly drinkers, whereas RAB25 expression was significantly higher in social drinkers, compared to occasional ones. The expression of RABL2A was significantly reduced in PDAC from diabetic patients, whereas RAB26 was significantly lower in pancreatitis patients. More importantly, a significant association of high expression of RAB21, RAB22A, and RAB25, and low expression of RAB6B, RABL2A, and RABL2B was observed with poorer survival of PC patients. Together, our study suggests potential diagnostic and prognostic significance of RABs in PDAC, warranting further investigations to define their functional and mechanistic significance.

scholarly journals Rab17, a novel small GTPase, is specific for epithelial cells and is induced during cell polarization.

1993 ◽  
Vol 121 (3) ◽  
pp. 553-564 ◽  
Author(s):  
A Lütcke ◽  
S Jansson ◽  
R G Parton ◽  
P Chavrier ◽  
A Valencia ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Small Gtpases ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Rab Proteins ◽  
Transport Pathways ◽  
Basolateral Plasma Membrane ◽  
Developing Kidney ◽  
Kidney Liver

The rab subfamily of small GTPases has been demonstrated to play an important role in the regulation of membrane traffic in eukaryotic cells. Compared with nonpolarized cells, epithelial cells have distinct apical and basolateral transport pathways which need to be separately regulated. This raises the question whether epithelial cells require specific rab proteins. However, all rab proteins identified so far were found to be equally expressed in polarized and nonpolarized cells. Here we report the identification of rab17, the first epithelial cell-specific small GTPase. Northern blot analysis on various mouse organs, revealed that the rab17 mRNA is present in kidney, liver, and intestine but not in organs lacking epithelial cells nor in fibroblasts. To determine whether rab17 is specific for epithelial cells we studied its expression in the developing kidney. We found that rab17 is absent from the mesenchymal precursors but is induced upon their differentiation into epithelial cells. In situ hybridization studies on the embryonic kidney and intestine revealed that rab17 is restricted to epithelial cells. By immunofluorescence and immunoelectron microscopy on kidney sections, rab17 was localized to the basolateral plasma membrane and to apical tubules. Rab proteins associated with two distinct compartments have been found to regulate transport between them. Therefore, our data suggest that rab17 might be involved in transcellular transport.

scholarly journals Significantly different expression levels of microRNAs associated with vascular invasion in hepatocellular carcinoma and their prognostic significance after surgical resection

2019 ◽  
Author(s):  
Sung Kyu Song ◽  
Woon Yong Jung ◽  
Seung-Keun Park ◽  
Chul-Woon Chung ◽  
Yongkeun Park
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatic Resection ◽  
Vascular Invasion ◽  
Prognostic Significance ◽  
Tnm Stage ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Roc Curve Analysis ◽  
Aberrant Expression ◽  
Advanced Tumor

ABSTRACTBackgroundAlthough gross vascular invasion (VI) has prognostic significance in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between gross VI and aberrant expression of microribonucleic acids (miRNAs and miRs). Thus, the objective of this study was to identify miRNAs selectively expressed in HCC with gross VI and investigate their prognostic significance.Materials and MethodsEligible two datasets (accession number: GSE20594 and GSE67140) were collected from the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO) database to compare miRNAs expression between HCC with and without gross VI. Differentially expressed miRNAs were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Prognostic significance and predicted functions of selected miRNAs for HCC were also investigated.ResultsThirty-five miRNAs were differentially expressed between HCC with and without gross VI in both datasets. Among them, four miRNAs were validated using TCGA database. miR-582 was upregulated to a greater extent while miR-99a, miR-100, and miR-148a were downregulated to a greater extent in patients with HCC and gross VI than in those with HCC but no VI. Receiver operating characteristic (ROC) curve analysis showed discriminatory power of these miRNAs in predicting gross VI. Multivariate survival analysis revealed that types of surgery, advanced tumor node metastasis (TNM) stage, and miR-100 underexpression were independently associated with tumor recurrence. It also revealed that types of surgery, advanced TNM stage, miR-100 underexpression, and miR-582 overexpression were independent risk factors for overall survival (OS) after hepatic resection for HCC. A text mining analysis revealed that these miRNAs were linked to multifaceted hallmarks of cancer, including “invasion and metastasis.”ConclusionsmiR-100 underexpression and miR-582 overexpression were associated with gross VI and poor survival of patients after hepatic resection for HCC.

scholarly journals Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ryuk Jun Kwon ◽  
Eun-Ju Park ◽  
Sang Yeoup Lee ◽  
Youngin Lee ◽  
Chungsu Hwang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Elevated Serum ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Chi Square ◽  
Altered Expression ◽  
Increased Risk ◽  
Niemann Pick

Abstract Background Colorectal cancer (CRC) is a malignancy of the large intestine, whose development and prognosis have been demonstrated to be associated with altered lipid metabolism. High cholesterol intake is associated with an increased risk of CRC, and elevated serum cholesterol levels are known to be correlated with risk of developing CRC. Niemann-Pick C1-Like 1 (NPC1L1), a target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, whether the altered expression of NPC1L1 affects CRC development and prognosis is currently unknown. Methods Data corresponding to patients with CRC were obtained from The Cancer Genome Atlas (TCAG). Datasets from the Genome Data Analysis Center (GDAC) platform were analyzed to compare the expression of NPC1L1 in normal and CRC tissues using the Mann–Whitney U test and chi-square test. Further, the datasets from the Gene Expression Omnibus (GEO) database were analyzed. The log-rank test and multivariate Cox proportional hazard regression analysis were performed to determine whether NPC1L1 significantly affects the prognosis of CRC. Results The expression of NPC1L1 was found to be upregulated in CRC and was significantly associated with the N and pathological stages but not with the histological type, age, and sex. Increased NPC1L1 expression in CRC was related to poor patient survival, as evidenced by the Kaplan–Meier and multivariate regression analyses. Conclusions As high expression of NPC1L1 was associated with CRC development, pathological stage, and prognosis, NPC1L1 can serve as an independent prognostic marker for CRC.

scholarly journals Expression of Genomic Instability-Related Molecules: Cyclin F, RRM2 and SPDL1 and Their Prognostic Significance in Pancreatic Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 859
Author(s):  
Anna Klimaszewska-Wiśniewska ◽  
Karolina Buchholz ◽  
Izabela Neska-Długosz ◽  
Justyna Durślewicz ◽  
Dariusz Grzanka ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Mrna Levels ◽  
Poor Overall Survival ◽  
Cyclin F

In the present study, we aimed to assess the selected components of cell cycle machinery, checkpoint, DNA repair, and synthesis, namely RRM2, cyclin F, and SPDL1 in pancreatic adenocarcinomas (PAC) by in-house immunohistochemistry (IHC) and bioinformatic analysis of public datasets, in terms of expression, correlation with clinicopathological parameters, and patient survival. Sixty eight patients with pancreatic ductal adenocarcinoma (PDAC) were included in our cohort study, and IHC was performed on tissue macroarrays. RNA-Seq-based transcriptome data for 177 PACs were retrieved from the Cancer Genome Atlas (TCGA). We found cyclin F, RRM2, and SPDL1 to be overexpressed at both protein and mRNA levels in tumor tissues compared to respective controls. Based on TCGA dataset, we have demonstrated that CCNF, RRM2, and SPDL1 are potent independent prognostic markers for poor overall survival, both by themselves and even more in combination with each other. Furthermore, high CCNF mRNA expression was associated with features of cancer progression. By contrast, overexpression of cyclin F or SPDL1 proteins denoted a good prognosis in PDAC patients; however, in the case of the former protein, the results did not reach statistical significance. Specifically, high levels of SPDL1 protein emerged as the most powerful independent prognostic factor associated with a better outcome. If validated, the CCNF/RRM2/SPDL1 three-gene panel developed in this study, as well as SPDL1 protein, may provide significant clinical implications for the prognosis prediction of PAC patients.

scholarly journals Alternative polyadenylation drives oncogenic gene expression in pancreatic ductal adenocarcinoma

2019 ◽  
Author(s):  
Swati Venkat ◽  
Arwen A. Tisdale ◽  
Johann R. Schwarz ◽  
Abdulrahman A. Alahmari ◽  
H. Carlo Maurer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Polyadenylation ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Tumor Type ◽  
Mirna Regulation ◽  
Sequencing Data ◽  
Altered Expression ◽  
Cancer Genome Atlas

ABSTRACTAlternative polyadenylation (APA) is a gene regulatory process that dictates mRNA 3’-UTR length, resulting in changes in mRNA stability and localization. APA is frequently disrupted in cancer and promotes tumorigenesis through altered expression of oncogenes and tumor suppressors. Pan-cancer analyses have revealed common APA events across the tumor landscape; however, little is known about tumor type-specific alterations that may uncover novel events and vulnerabilities. Here we integrate RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA) to comprehensively analyze APA events in 148 pancreatic ductal adenocarcinomas (PDAs). We report widespread, recurrent and functionally relevant 3’-UTR alterations associated with gene expression changes of known and newly identified PDA growth-promoting genes and experimentally validate the effects of these APA events on expression. We find enrichment for APA events in genes associated with known PDA pathways, loss of tumor-suppressive miRNA binding sites, and increased heterogeneity in 3’-UTR forms of metabolic genes. Survival analyses reveal a subset of 3’-UTR alterations that independently characterize a poor prognostic cohort among PDA patients. Finally, we identify and validate the casein kinase CK1α as an APA-regulated therapeutic target in PDA. Knockdown or pharmacological inhibition of CK1α attenuates PDA cell proliferation and clonogenic growth. Our single-cancer analysis reveals APA as an underappreciated driver of pro-tumorigenic gene expression in PDA via the loss of miRNA regulation.

scholarly journals Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

2020 ◽  
Author(s):  
Jun-qi Liu ◽  
Xi-wen Liao ◽  
Xiang-kun Wang ◽  
Cheng-kun Yang ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Characteristics ◽  
Prognostic Significance ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Joint Effects ◽  
Prognosis Prediction ◽  
Genome Wide

Abstract Background: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA).Methods: A total of 112 PDAC patients from TCGA were included in the analysis.The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) to identify potential underlying mechanisms.Results: High expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total score calculated. Genome-wide co-expression and GSEA analyses suggested that the GPC2 mechanisms affecting prognosis involved sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway.Conclusion: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and the combination of these genes showed a higher efficiency for prognosis prediction.

Prognostic Significance of Plasma Fibrinogen/Serum Albumin Ratio in the Postoperative Outcome of Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 40 (12) ◽  
pp. 7017-7023
Author(s):  
KOICHI TOMITA ◽  
SHIGETO OCHIAI ◽  
TAKAHIRO GUNJI ◽  
KOSUKE HIKITA ◽  
TOSHIMICHI KOBAYASHI ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Significance ◽  
Postoperative Outcome ◽  
Plasma Fibrinogen ◽  
Ductal Adenocarcinoma ◽  
Albumin Ratio

scholarly journals The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zhang ◽  
Zhaohui Zhong ◽  
Mei Li ◽  
Jingyi Chen ◽  
Tingru Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
The Cancer Genome Atlas ◽  
Actin Dynamics ◽  
Elevated Expression ◽  
Sw480 Cells ◽  
And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

scholarly journals miR-29a sensitizes the response of glioma cells to temozolomide by modulating the P53/MDM2 feedback loop

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiudan Chen ◽  
Weifeng Wang ◽  
Shuying Chen ◽  
Xiaotong Chen ◽  
Yong Lin
Keyword(s):  
Molecular Mechanism ◽  
Feedback Loop ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Aberrant Expression ◽  
Altered Expression ◽  
P53 Signaling

AbstractRecently, pivotal functions of miRNAs in regulating common tumorigenic processes and manipulating signaling pathways in brain tumors have been recognized; notably, miR‐29a is closely associated with p53 signaling, contributing to the development of glioma. However, the molecular mechanism of the interaction between miR-29a and p53 signaling is still to be revealed. Herein, a total of 30 glioma tissues and 10 non-cancerous tissues were used to investigate the expression of miR‐29a. CCK-8 assay and Transwell assay were applied to identify the effects of miR-29a altered expression on the malignant biological behaviors of glioma cells in vitro, including proliferation, apoptosis, migration and invasion. A dual-luciferase reporter assay was used to further validate the regulatory effect of p53 or miR-29a on miR-29a or MDM2, respectively, at the transcriptional level. The results showed that miR-29a expression negatively correlated with tumor grade of human gliomas; at the same time it inhibited cell proliferation, migration, and invasion and promoted apoptosis of glioma cells in vitro. Mechanistically, miR-29a expression was induced by p53, leading to aberrant expression of MDM2 targeted by miR-29a, and finally imbalanced the activity of the p53-miR-29a-MDM2 feedback loop. Moreover, miR-29a regulating p53/MDM2 signaling sensitized the response of glioma cells to temozolomide treatment. Altogether, the study demonstrated a potential molecular mechanism in the tumorigenesis of glioma, while offering a possible target for treating human glioma in the future.

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