High-Expression HBO1 Predicts Poor Prognosis in Gastric Cancer

2019 ◽  
Vol 152 (4) ◽  
pp. 517-526 ◽  
Author(s):  
Yan Wang ◽  
Sufang Chen ◽  
Wei Tian ◽  
Qing Zhang ◽  
Chunyi Jiang ◽  
...  

Abstract Objectives Our goal was to assess the expression of histone acetyltransferase binding to origin recognition complex 1 (HBO1) in gastric cancer and the effect on prognosis for the patients. Methods We used quantitative reverse transcription polymerase chain reaction, Western blot, and tissue microarray immunohistochemistry to investigate the expressions of HBO1 messenger RNA (mRNA) and protein in gastric cancer tissues. Online resources, including Oncomine and Kaplan-Meier Plotter, were used to further assess the correlation between HBO1 expression and the prognosis of the patients with gastric cancer. Results HBO1 mRNA and protein expressions in gastric cancer tissues were both significantly higher than those in normal tissues. The correlations between high HBO1 expression and differentiation, invasive depth (T), lymph node metastasis (N), distant metastasis (M), TNM staging, and serum carcinoembryonic antigen levels were positive. High HBO1 expression was negatively correlated with survival time in patients with gastric cancer. Conclusions HBO1 might be a valuable biomarker to evaluate the prognosis of patients with gastric cancer.

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Xiuchong Yu ◽  
Haixiang Ding ◽  
Yijiu Shi ◽  
Liangwei Yang ◽  
Jiaming Zhou ◽  
...  

Background. Gastric cancer (GC) is one of the global mortality diseases and has a poor prognosis due to the lack of ideal tumor biomarkers. Numerous studies have shown that long noncoding RNAs (lncRNAs) can affect the occurrence and development of cancer through a variety of signaling pathways. The abnormal expression and specificity of lncRNAs in tumors make them potential biomarkers of cancers. Nevertheless, the diagnostic roles of lncRNAs in GC have been poorly understood. So this study focuses on the clinical diagnostic value of lncRNAs in GC. Materials and Methods. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to investigate the expression of the linc-ROR (long intergenic noncoding RNA, regulator of reprogramming) in 105 paired GC tissues and adjacent normal tissues. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were established to assess the diagnostic value of linc-ROR. The relationship between expression of linc-ROR and clinicopathological factors of patients with GC was further explored. Kaplan-Meier analysis was performed to evaluate the prognostic value of linc-ROR expression. Results. The linc-ROR expression level was significantly decreased in GC tissues compared with its adjacent nontumor tissues ( n = 105 , P < 0.001 ). We also discovered that linc-ROR was evidently downregulated in 68.6% (72/105) of GC tissues. The AUC’s value of linc-ROR was up to 0.6495, with sensitivity and specificity of 0.7524 and 0.5143, respectively. Intriguingly, the linc-ROR expression levels were obviously associated with tumor differentiation ( P = 0.004 ). Notably, the overall survival rate of GC patients with high expression of linc-ROR was significantly higher than those with low expression. Conclusion. Our data revealed that linc-ROR has clinical potential as a biomarker for the diagnosis of GC and assessment of its prognosis.


2021 ◽  
Author(s):  
zhang jing ◽  
Fu xi feng

Abstract Background.The AMIGO2 extracellular domain has a leucine - rich repetitive domain (LRR) and encodes a type 1 transmembrane protein , and is a member of the AMIGO gene family .Although the abnormal expression of AMIGO2 is associated with multiple tumors , the relationship with pancreatic cancer is not clear .Methods.The expression of AMIGO2 mRNA and proteins in pancreatic cancer was analyzed using NCBI GEO database and GEPIA2、Human Protein Atlas database.The RNA sequencing data of pancreatic cancer and clinical data of pancreatic cancer patients in TCGA public database were retrospectively analyzed. AMIGO2 gene expression data and their corresponding clinical information in the sample were analyzed retrospectively. The diagnostic value of AMIGO2 expression in pancreatic cancer patients was determined by receiver operating characteristic (ROC) curve analysis. The effects of AMIGO2 expression differences on survival time of pancreatic cancer patients were analyzed by Kaplan-Meier Plotter database and GEPIA2 database.The correlation between AMIGO2 gene and TP53 mutation in pancreatic cancer was analyzed by UALCAN database and TIMER database. The similar genes of AMIGO2 in pancreatic cancer were analyzed by GEPIA2 database, and the biological behavior, cellular composition, molecular function enrichment analysis and protein interaction of similar genes were analyzed by DAVID database and Metascape database. enrichment analysis of AMIGO2 similar gene pathways using KEGG database. The MSIGDB cancer coexpression module in Harmonizome database and TIMER database were used to study the gene coexpression of AMIGO2 in pancreatic cancer. AMIGO2 transcription factors were predicted using the JASPER database. The pathway of AMIGO2 transcription factors and co-expression genes was studied by KEGG database.Results. The expression of AMIGO2 (GSE16515, GSE15471) in pancreatic cancer tissues was significantly higher than that in normal tissues (P < 0.05). The GEPIA2 database also confirmed that the expression of AMIGO2 in pancreatic cancer tissues was significantly higher than that in normal tissues. The expression level of AMIGO2 gene was correlated with lymph node metastasis and histological grade of pancreatic cancer (P<0.05). The high expression of AMIGO2 protein in pancreatic cancer was confirmed in Human Protein Atlas database. The overall survival rate and progression-free survival rate of pancreatic cancer patients with high expression of AMIGO2 were significantly shorter than those of patients with low expression of AMIGO2 in Kaplan-Meier Plotter database and GEPIA2 database. In the gene ontology analysis, it is found that AMIGO2 is involved in cell adhesion, proliferation, migration, apoptosis and other biological processes. KEGG analysis pathway is concentrated in the focal adhesion pathway, mitotic cell cycle changes, and the regulation of cell protein localization. Abnormal expression of AMIGO2 was found in pancreatic cancer caused by TP53 mutation in UALCAN and TIMER databases.In JASPAR database, we predicted that there are 10 transcription sites between AMIGO2 and transcription factor MYB. In addition, there are positive genes related to AMIGO2 in TIMER database and transcription factor MYB regulates tumor cell proliferation and apoptosis in PI3K-Akt signal transduction pathway and WNT signal pathway in pancreatic cancer.


2020 ◽  
Vol 19 ◽  
pp. 153303382092342
Author(s):  
Guo Chen ◽  
Jinliang Wan ◽  
Zhenbo Wang ◽  
Lei Li ◽  
Hongying Jia ◽  
...  

Background: Gastric cancer is one of the most common malignancies worldwide with high mortality. Therefore, identifying cancer-related biomarkers for predicting prognosis and progression of gastric cancer is essential. This study aimed to investigate the clinical value and functional role of microRNA-3196 in gastric cancer. Methods: The relative expression levels of microRNA-3196 in gastric cancer tissues and adjacent normal tissues were detected by quantitative reverse transcription-polymerase chain reaction. In this study, quantitative reverse transcription-polymerase chain reaction, cell proliferation assay, and Transwell migration and invasion assays were performed to explore microRNA-3196 expression level and its effects on cell proliferation, migration, and invasion in gastric cancer cells. The Kaplan-Meier method and multivariate Cox regression analyses were used to explore the prognostic significance of microRNA-3196 in gastric cancer. Dual-luciferase report assay was performed to validate the potential target gene regulated by microRNA-3196 in gastric cancer. Results: The expression of microRNA-3196 was downregulated in gastric cancer tissues and cell lines. Downregulation of microRNA-3196 was associated with lymph node metastasis and Tumor Node Metastasis (TNM) stage. The Kaplan-Meier curve analysis indicated that patients with low expression of microRNA-3196 had a poor prognosis, and the Cox regression analysis results showed microRNA-3196 expression was an independent prognostic factor of gastric cancer. Moreover, overexpression of microRNA-3196 inhibited cell proliferation, migration, and invasion, while knockdown of microRNA-3196 promoted these cellular behaviors in AGS and MKN45 cells. OTX1 may be a potential target gene regulated by microRNA-3196 in gastric cancer. Conclusions: These results suggested that microRNA-3196 might not only a tumor suppressor in gastric cancer cells by modulating OTX1 but also might be an independent prognostic biomarker and therapeutic target of gastric cancer.


2020 ◽  
Vol 68 (8) ◽  
pp. 1357-1363
Author(s):  
Feng-Yu Cao ◽  
Yong-Bin Zheng ◽  
Chao Yang ◽  
Su-Yang Huang ◽  
Xiao-Bo He ◽  
...  

Accumulating studies have shown that the dysregulation of microRNAs is related to the carcinogenesis and development of gastric cancer (GC), and the role of miR-635 in GC remains largely unknown. miR-635 and Kinesin Family Member C1 (KIFC1) mRNA expression in GC tissues and paracancerous tissues and cells were detected by quantitative real-time PCR. KIFC1 protein expression in GC tissues and paracancerous normal tissues and cells was detected by immunohistochemistry and western blot. Cell proliferation was monitored by Cell Counting Kit-8 assay and 5-bromo-2′-deoxyuridine assay. Transwell assay was employed to detect the migration and invasion of GC cells. The dual-luciferase reporter gene assay was adopted to detect the targeting relationship between miR-635 and KIFC1. Compared with paracancerous tissues, miR-635 expression was remarkably decreased in GC tissues; conversely, KIFC1 expression was significantly increased. Compared with human normal gastric epithelial cell GSE-1, miR-635 expression was markedly decreased in GC cell lines. Meanwhile, KIFC1 expression was significantly increased, and the Kaplan-Meier Plotter database showed that its high expression was remarkably associated with poor prognosis. Additionally, miR-635 can negatively regulate KIFC1. miR-635 can target KIFC1 to inhibit proliferation, migration and invasion of GC cells. Collectively, miR-635 is lowly expressed in GC, and it inhibits proliferation, migration and invasion of GC cells via regulating KIFC1.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1820
Author(s):  
Chengcheng Hao ◽  
Yuxin Cui ◽  
Jane Lane ◽  
Shuqin Jia ◽  
Jiafu Ji ◽  
...  

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Xin Zhao ◽  
Dongyang Tang ◽  
Xiaofei Chen ◽  
Shaoqing Chen ◽  
Cheng Wang

Introduction. Baicalein has been shown to have antitumor activities in several cancer types. However, its acting mechanisms remain to be further investigated. This work is aimed at exploring the functional long noncoding RNA (lncRNA)/microRNA (miRNA)/messenger RNA (mRNA) triplets in response to baicalein in hepatocellular carcinoma (HCC) cell to understand the mechanisms of baicalein in HCC. Methods. Differentially expressed lncRNAs (DELs) and miRNAs (DEMs) in HCC cell treated with baicalein were first screened using GSE95504 and GSE85511, respectively. miRNA targets for DELs were predicted and intersected with DEMs, after which the miRNA expression was validated using ENCORI and its prognostic value was assessed using Kaplan-Meier plotter. Potential miRNA targets were predicted by 3 prediction tools, after which expression level was validated at UALCAN and Human Protein Atlas. Kaplan-Meier plotter was used to evaluate the effects of these genes on overall survival and recurrence-free survival of HCC patients. Enrichment analyses for these genes were performed at DAVID. Results. Here, we identified 14 overlapping DELs and 26 overlapping DEMs in the baicalein treatment group than those in the DMSO treatment group. Subsequently, by analyzing expression and clinical significance of miRNAs, hsa-miR-4443 was found as a highly potential miRNA target. Then, targets of hsa-miR-4443 were predicted and analyzed, and we found AKT1 was the most potential target for hsa-miR-4443. Hence, the lncRNAs-hsa-miR-4443-AKT1 axis that can respond to baicalein was established. Conclusion. Collectively, we elucidated a role of lncRNAs-hsa-miR-4443-AKT1 pathway in response to baicalein treatment in HCC, which could help us understand the roles of baicalein in inhibiting cancer progression and may provide novel insights into the mechanisms behind HCC progression.


2021 ◽  
Vol 11 ◽  
Author(s):  
Min Wu ◽  
Pan Zhang ◽  
Penghui Wang ◽  
Zhen Fang ◽  
Yaqin Zhu

ObjectiveThis study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).MethodsELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.ResultsBioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values&gt;0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.ConclusionFEN1 might be a novel diagnostic and prognostic marker for BC.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang-Jie Wu ◽  
Ai-Tao Nai ◽  
Gui-Cheng He ◽  
Fei Xiao ◽  
Zhi-Min Li ◽  
...  

Abstract Background Dihydropyrimidinase like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored. Methods Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan–Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. Results In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan–Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cells, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2. Conclusions In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target. Highlights Expression of DPYSL2 was considerably lower in LUAD than in normal tissues. Investigation of multiple databases showed a high diagnostic value of DPYSL2 in LUAD. DPYSL2 can independently predict the LUAD outcomes. Immune-related mechanisms may be potential ways for DPYSL2 to play a role in LUAD.


2020 ◽  
Author(s):  
Qiongzi Wang ◽  
Xueshan Qiu

Abstract Iroquoishomeobox transcription factor family (IRXs)have been increasingly reported to play roles in suppressing or promoting a variety of cancers, however, little is known about their expression and prognostic value in terms of human lung cancer. In this study, Oncomine, GEPIA, Kaplan-Meier plotter, and cBioPortal databases were used to analyze the different expression patterns and prognostic values of six IRXs in NSCLC and examine their related functions and pathways using GO enrichment. Compared with normal lung cancer tissues, the expression of IRX1 and IRX2 in NSCLC tissues was significantly lower and was positively correlated with the 10-year survival rate of patients. Higher expression of IRX4 was related to terminal tumors, and suggested a poor prognosis. It was also found that IRXs may play a tumor-suppressive role in the localization of cytoplasm in NSCLC, while localization in the nucleus suggests a more malignant behavior. Together these results suggest that IRX1 and IRX2 may be prognostic indicators of LUAD, and that IRX4 could be a potential target for LUAD treatment.


2018 ◽  
Author(s):  
Shoufeng Zhao ◽  
Zhipeng Wang

ABSTRACTOvarian cancer (OC) is commonly diagnosed at an advanced stage due to a lack of effective biomarkers and specificity required for accurate clinical diagnosis. The purpose of this study was to estimate the diagnosis and prognosis of the NaPi- II b in ovarian cancer. Herein, by performing data mining using the databases of Oncomine and Cancer Cell Line Encyclopedia (CCLE), we are for the first time to report that the expression level of NaPi- II b transcripts in a variety of tumor types compared with the normal controls. Based on Kaplan-Meier plotter, we investigated the prognostic values of NaPi- II b specifically high expressed in OC patients. The results of the Oncomine analysis showed that relative expression of NaPi- II b was distinctly high in OC tissues vs. normal tissues. CCLE analysis indicated that the expression of NaPi- II b in OC cell lines expressed the highest level in all cancer lines. In overall survival (OR) analysis, NaPi- II b mRNA high expressions were correlated to worse OR in OC patients. These results indicate that NaPi- II b may be a novel potential biomarker for determining the diagnosis and predicting the prognosis of OC.


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