scholarly journals LncRNA HCP5 : A Potential Biomarker for Diagnosing Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shiyi Qin ◽  
Lei Yang ◽  
Shan Kong ◽  
Yanhua Xu ◽  
Bo Liang ◽  
...  

BackgroundIt has been reported that long non-coding RNAs (lncRNAs) can be regarded as a biomarker and had particular clinical significance for early screening and gastric cancer (GC) diagnosis. Therefore, this study aimed to investigate whether serum HCP5 could be a new diagnostic biomarker.MethodsFiltered out the HCP5 from the GEO database. The specificity of HCP5 was verified by real-time fluorescence quantitative PCR (qRT-PCR), and then the stability of HCP5 was verified by room temperature storage and repeated freeze-thaw experiments. Meanwhile, the accuracy of HCP5 was verified by agarose gel electrophoresis (AGE) and Sanger sequencing. Simultaneously, the expression level of serum HCP5 was detected by qRT-PCR in 98 patients with primary gastric cancer, 21 gastritis patients, 82 healthy donors, and multiple cancer types. Then, the methodology analysis was carried on. Moreover, receiver operating characteristic (ROC) was used to evaluate its diagnostic efficiency.ResultsqRT-PCR method had good repeatability and stability in detecting HCP5. The expression level of HCP5 in the serum of gastric cancer patients was remarkably higher than that of healthy controls, and it could distinguish gastritis patients from healthy donors. Besides, the expression of HCP5 was increased dramatically in MKN-45 and MGC-803. The FISH assay showed that HCP5 was mainly distributed in the cytoplasm of MKN-45 and BGC-823 cells. When HCP5 was combined with existing tumor markers, the diagnostic efficiency of HCP5 was the best, and the combined diagnosis of carcinoembryonic antigen (CEA), carbohydrate antigen199 (CA199), and HCP5 can significantly improve the diagnostic sensitivity. Besides, compared with the expression levels of thyroid cancer (THCA), colorectal cancer (CRC), and breast cancer (BRCA), serum HCP5 in gastric cancer was the most specific. Moreover, the high expression of serum HCP5 was related to differentiation, lymph node metastasis, and nerve invasion. The term of serum HCP5 after the operation was significantly lower than that of patients with primary gastric cancer.ConclusionSerum HCP5 can be used as a potential biomarker of non-invasive fluid biopsy, which had a unique value in the early diagnosis, development, and prognosis of gastric cancer.

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinliang Gu ◽  
Shuo Ma ◽  
Bo Liang ◽  
Shaoqing Ju

BackgroundGastric cancer (GC) is one of the most common malignant tumors globally and the third leading cause of cancer-related death. Currently, the sensitivity and specificity of diagnostic markers for GC are low, so it is urgent to find new biomarkers with higher sensitivity and specificity. tRNA-derived small RNAs are a kind of small non-coding RNAs derived from tRNAs. It is abundant in cancer cells and body fluids. Our goal is to find the differentially expressed tRNA-derived small RNAs in GC to explore their potential as a GC biomarker.MethodsQuantitative real-time PCR was used to detect the expression level of hsa_tsr016141. The molecular characteristics of hsa_tsr016141 were verified by agarose gel electrophoresis, Sanger sequencing, Actinomycin D Assay, and Nuclear and Cytoplasmic RNA Separation Assay. The diagnostic efficiency of hsa_tsr016141 was analyzed through receiver operating characteristic.ResultsThe expression level of hsa_tsr016141 in GC tissues and serum was significantly increased. The serum expression level showed a gradient change between GC patients, gastritis patients, and healthy donors and was positively correlated with the degree of lymph node metastasis and tumor grade. ROC analysis showed that the serum expression level of hsa_tsr016141 could significantly distinguish GC patients from healthy donors or gastritis patients. Besides, the expression level of hsa_tsr016141 in GC patients decreased significantly after the operation (P<0.0001).ConclusionsSerum hsa_tsr016141 has good stability and specificity and can be used for dynamic monitoring of GC patients, suggesting that serum hsa_tsr016141 can be a novel biomarker for GC diagnosis and postoperative monitoring.


2020 ◽  
Author(s):  
Yanhua Xu ◽  
Shan Kong ◽  
Xinyue Qin ◽  
Shaoqing Ju

Abstract Background: Due to the lack of specific and sensitive detection indicators, most patients with gastric cancer (GC) are already in the advanced stage at the time of diagnosis, resulting in a higher mortality. Therefore, it is urgent to search for effective diagnostic biomarkers with high specificity that can be applied in clinic. Methods: We screened out circ_0004771 through circRNA sequencing performed on three pairs of GC tissues and corresponding paracancerous tissues. Both exonuclease digestion assay, agarose gel electrophoresis (AGE) and sanger sequencing verified the potential of circ_0004771 being a biomarker. Additionally, we established quantitative real-time fluorescent Polymerase Chain Reaction (qRT-PCR) to detect the expression level of circ_0004771 and evaluated the methodology. What’s more, we collected plasma samples from GC patients, precancerous patients and gastritis patients, and we constructed the receiver operating characteristic curve (ROC) to appraise its diagnostic efficacy. Meanwhile, we collected the clinicopathological data of the patients to analyze the relationship between the expression level of circ_0004771 and the pathological parameters of the patients. Results: The expression level of circ_0004771 is up-regulated both in GC tissues and cells compared to normal controls. Circ_0004771 can be served as a promising biomarker because of its stable cyclic structure and longer half-life. The expression level of plasma circ_0004771 can distinguish between GC patients and precancerous patients, GC patients and gastritis patients. The diagnostic efficiency of circ_0004771 is higher than that of CEA and CA199. Higher diagnostic efficiency can be achieved in combination diagnosis. The expression level of plasma circ_0004771 in GC patients decreased after surgery, which can track the recovery condition of patients. Besides, the downstream regulatory forecast indicates that circ_0004771 may act as miRNA sponge to regulate the progression of GC.Conclusion: Plasma circ_0004771 can be served as a less invasive tumor biomarker with high diagnostic values.


2021 ◽  
Author(s):  
Zongxian Zhao ◽  
Shuliang Li ◽  
Shilong Li ◽  
Jun Wang ◽  
Hai Lin ◽  
...  

Abstract BackgroundGastric cancer (GC) is one of the most common and fatal cancers worldwide and effective biomarkers aids in GC management and prognosis. Hence, we explored the role and function of cadherin 6 (CDH6) in diagnosis and prognosis of gastric cancer. MethodsThe expression level of CDH6 in GC tissue and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas dataset (TCGA). The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and expression of CDH6 were evaluated statistically and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. Forty-four GC tissues, corresponding adjacent normal tissues (n=20), and detailed clinical information were collected from Tianjin Medical University General Hospital, CDH6 expression level was detected for further validation. ResultsCDH6 was upregulated in GC samples compared with normal gastric tissue, and GSEA identified the citrate cycle tricarboxylic (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism oxidative phosphorylation, and pentose phosphate pathway as differentially enriched in GCs. According to the area under the ROC curve (AUC) (AUC=0.829 in TCGA and 0.966 in GSE54129), CDH6 had high diagnostic efficiency. Patients with high expression of CDH6 was associated with higher T classification and worse prognoses than those with low CDH6 expression in GC. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). ConclusionCDH6 was upregulated in GC and high CDH6 expression indicated higher T classification and worse prognoses. CDH6 could be a potentially independent molecular biomarker for diagnosis and prognosis of GC.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Gang Wang ◽  
Dan Sun ◽  
Wenhui Li ◽  
Yan Xin

The AT-hook transcription factor, AKNA, is a nuclear protein that affects a few physiological and pathological processes including cancer. Here, we investigated the role of AKNA in gastric cancer (GC). By using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, AKNA was found deregulated in both GC cell lines and 32 paired GC tissues. Subsequently, Kaplan-Meier analysis and clinicopathological analysis were conducted using both 32 GC cases’ data above and RNA-Seq data of AKNA in 354 GC patients and the corresponding clinical-pathological data obtained from The Cancer Genome Atlas (TCGA), and AKNA expression was found closely related to location, metastasis, and TNM staging of GC. Then, the potential molecular mechanisms of AKNA in GC were explored by gene set enrichment analysis (GSEA), qRT-PCR, and Western blot assays. AKNA was found to be a hub gene related to homotypic cell to cell adhesion, regulation of cell to cell adhesion, leukocyte cell to cell adhesion, and regulation of T cell proliferation in GC. GO analysis revealed that AKNA involved in the regulation of epithelial-mesenchymal transition (EMT)-related pathways including chemokine signaling pathway, cytokine to cytokine receptor interaction, cell adhesion molecules, and jak-stat signaling pathway in GC. To explore the regulation of AKNA expression, Targetscan and TargetMiner were used to predict the possible miRNA which targeted AKNA and found the expression of AKNA was negatively correlated to miR-762 which could be sponged by circTRNC18. In conclusion, AKNA could function as a tumor suppressor by modulating EMT-related pathways in GC. The expression of AKNA might be regulated by circTRNC18/miR-762 axis. AKNA could serve as a potential biomarker and an effective target for GC diagnosis and therapy.


2015 ◽  
pp. bgv139 ◽  
Author(s):  
Yuji Toiyama ◽  
Koji Tanaka ◽  
Takahito Kitajima ◽  
Tadanobu Shimura ◽  
Hiroki Imaoka ◽  
...  

2018 ◽  
Vol 22 (3) ◽  
pp. 375-384
Author(s):  
Jingjing Zhao ◽  
Cong Mai ◽  
Desheng Weng ◽  
Changlong Chen ◽  
Ziqi Zhou ◽  
...  

2020 ◽  
Author(s):  
Xuan Chen ◽  
Lizuan Chen ◽  
Zeming Ren ◽  
Yeling Tong ◽  
Guanhai Dai ◽  
...  

Abstract BACKGROUND AND PURPOSE: Stmn1 is over-expressed in almost all pathological stages during gastric cancer development, such as chronic atrophic gastritis, dysplasia, and gastric cancer. IM is an important precancerous lesion of gastric cancer, however, whether Stmn1 was up-regulated or down-regulated in this stage is still unknown. We aimed to evaluate the expression level of Stmn1 in IM in vivo and its relationship with important gene of IM named Cdx2 in vitro.EXPERIMENTAL APPROACH: Wistar rats (n=12, sex in half) were gavaged with MNNG (167μg/ml) to induce IM model in stomach. After pathological examination with AB staining to confirm that the model was successful, relative expression level of Stmn1 was detected between normal group and model group using RT-qPCR. Human gastric cell line GES-1 was used to investigate whether Stmn1 influence expression level of IM essential gene Cdx2 by over-expressing or down-expressing experiments, RT-qPCR and western blot.KEY RESULTS: We have demonstrated that Stmn1 was up-regulated in IM model induced by MNNG in rats in vivo, and it could significantly up-regulate Cdx2 expression level in human gastric cell line GES-1 in vitro.CONCLUSIONS AND IMPLICATIONS: We demonstrated that Stmn1 was involved in IM in this model and it could up-regulating Cdx2 in human gastric cell line GES-1 in vitro. These results suggested that Stmn1 might be a potential biomarker or candidate treatment target of IM in stomach.


2021 ◽  
Author(s):  
Cai Xin ◽  
Tang Dongling ◽  
Chen Juanjuan ◽  
Li Huan ◽  
Hu Yuanhui ◽  
...  

Abstract Background There is an urgent need for new serum biomarkers for early screening of HBV-related hepatocellular carcinoma (HCC). Fibrinogen like protein 1 (FGL1) may develop the potential diagnostic value of alpha fetoprotein (AFP) in HBV-related HCC. Methods The TCGA database was used to screen out genes related to liver cancer and perform differential expression analysis. Enzyme-linked immunosorbent assay and chemiluminescence immunoassay were used to detect concentrations of FGL1 and AFP. Using immunofluorescence semi-quantitative method to detect the mean fluorescence intensity of FGL1. Result FGL1 is lower in tumor tissues than in normal tissues. The serum levels of FGL1 and AFP in patients with HBV-related HCC are significantly higher than others for each group. Compared with other groups, the area under the receiver operating curve (AUC) of FGL1 is higher than that of AFP when compared with the normal group, and the AUC of other groups is lower than that of AFP. The combination of the two can increase the AUC to 0.862 (95%CI, 0.786 ~ 0.918) in distinguishing benign liver disease from HBV-related HCC. The specificity of FGL1 and AFP in the diagnosis of HBV-related HCC is 98.39% and 70.97%, respectively. The specificity of the combination was 93.55%. In distinguishing the A and B stages in the BCLC staging, the combination of the two increased the AUC from 0.584 to 0.647. When distinguishing benign liver disease from HBV-related HCC, the AUC of FGL1 reached 0.849, with a specificity of 100%. Conclusion FGL1 can be used as a non-invasive biomarker for HCC. When combined with AFP, the diagnostic efficiency and specificity were improved.


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