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Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for gastric cancer.

ABSTRACT: Background:Gastric cancer (GC) is a common malignant cancer in the worldwide, especially in China. Patients with GC have poor prognosis, which is mainly due to lack of early diagnosis. Up to now, there is no good biomarker to detect GC at early stage. Apolipoprotein C1 (APOC1), a component of both triglyceride-rich lipoproteins and high-density lipoproteins, is reported to be involved in numerous biological processes. Methods:Expression of APOC1 mRNA was analyzed by in silicon assay. Concentration of APOC1 in serum was measured by ELISA assay. Expression of APOC1 protein in GC tissue array was checked by immunohistochemistry. Results:It was firstly found that concentration of APOC1 in serum was significantly higher in GC than that in control. Expression of APOC1 protein was also higher in GC than that in adjacent issues of GC and normal tissues using tissues array by immunohistochemistry. In addition, the expression of APOC1 is significantly associated with clinical stage (P=0.011), tumor classification (P=0.010), as well as with the lymph node metastasis (P=0.048). Area under the curve (AUC) of receiver operating characteristic (ROC) curve of APOC1 was 0.803. Furthermore, elevated APOC1 expression in GC was found to be correlated with decreased overall survival (P=0.00214). Conclusions:All these results suggested that APOC1 might be a potential serum biomarker to diagnose GC and a potential prognostic marker for GC.

SUBMITTER: Yi J

PROVIDER: S-EPMC6736826 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for gastric cancer.

Yi Jie J Ren Liwen L Wu Jie J Li Wan W Zheng Xiangjin X Du Guanhua G Wang Jinhua J

Annals of translational medicine 20190801 16

<h4>Background</h4>Gastric cancer (GC) is a common malignant cancer in the worldwide, especially in China. Patients with GC have poor prognosis, which is mainly due to lack of early diagnosis. Up to now, there is no good biomarker to detect GC at early stage. Apolipoprotein C1 (APOC1), a component of both triglyceride-rich lipoproteins and high-density lipoproteins, is reported to be involved in numerous biological processes.<h4>Methods</h4>Expression of APOC1 mRNA was analyzed by <i>in silicon< ...[more]

PMID: 31555694

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Project description:Background: Apolipoprotein C1 (APOC1) has been proved to play a critical role in gastric, breast, lung, and pancreatic cancer. However, the relationship between APOC1 and urinary tumors remains unclear. This study aimed to assess the diagnostic and prognostic value of APOC1 in urinary tumors. Methods: We performed a pan analysis of APOC1 mRNA expression in urinary cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) database. To further investigate the prognostic value of APOC1 expression in urinary cancers, the Kaplan-Meier plotter database was used. Furthermore, we collected the tumor and adjacent normal samples of 32 ccRCC patients to perform qRT-PCR and western blotting assays. A total of 72 cases with ccRCC were analyzed using tissue microarrays (TMAs). Results: Our results based on Kaplan-Meier plotter database indicated that a high expression of APOC1 may lead to poor overall survival (OS, p = 0.0019) in patients with ccRCC. Furthermore, the cancer stages and tumor grade of ccRCC appeared to be strongly linked with APOC1 expression according to UALCAN database. Hence, we reached a preliminary conclusion that APOC1 may play a key role in the tumorigenesis and progression of ccRCC. Furthermore, the Kaplan-Meier survival curve analyses of 72 clinical patients indicated that high expression of APOC1 was associated with poor progression-free survival (PFS, p = 0.007) and OS (p = 0.022). In addition, univariate Cox regression analysis confirmed the significant relationship between APOC1 expression and survival (p = 0.038). The TMAs analysis in combination with the patients' clinicopathological features was also performed. The expression of APOC1 was found to be significantly correlated with the tumor size (p = 0.018) and histological grade (p = 0.016). Conclusions: In conclusion, the findings of our study suggest that APOC1 may serve as a novel diagnostic and prognostic biomarker for ccRCC. Further evidence on the mechanism of APOC1 promoting tumor progression may transform it to a new therapeutic target for the treatment of ccRCC.

Project description:Objective: This study aimed to identify the hub gene in gastric cancer (GC) tumorigenesis. A biomarker prediction model was constructed and analyzed, and protein expression in histopathological samples was verified in a validation cohort. Methods: Differentially expressed genes (DEGs) were identified from GC projects in The Cancer Genome Atlas (TCGA) database. Functional enrichment analysis of DEGs was performed between the high- and low- Ribonuclease P protein subunit p30 (RPP30) expression groups. ROC analysis was performed to assess RPP30 expression to discriminate GC from normal tissues. Functional enrichment pathways and immune infiltration of DEGs were analyzed using GSEA and ssGSEA. Survival analysis and nomogram construction were performed to predict patient survival. Immunohistochemical staining of GC tissues was performed to validate RPP30 expression in GC and paracancerous samples. Results: Gene expression data and clinical information of 380 cases (375 GC samples and 32 para-cancerous tissues) were collected from TCGA database. The AUC for RPP30 expression was found to be 0.785. The G alpha S signaling pathway was the most significantly enriched signaling pathway. Primary therapy outcome (p < 0.001, HR = 0.243, 95% CI = 0.156-0.379), age (p = 0.012, HR = 1.748, 95% CI = 1.133-2.698), and RPP30 expression (p < 0.001, HR = 2.069, 95% CI = 1.346-3.181) were identified as independent prognostic factors. As a quantitative approach, a nomogram constructed based on RPP30 expression, age, and primary therapy outcome performed well in predicting patient survival. Nineteen of the 25 tissue samples from the validation cohort showed positive RPP30 expression in GC tissues, whereas 16 cases showed negative RPP30 staining in normal tissues. The difference between the two was statistically significant. Conclusion: High RPP30 expression was significantly correlated with disease progression and poor survival in GC, promoting tumorigenesis and angiogenesis via tRNA dysregulation. This study provides new and promising insights into the molecular pathogenesis of tRNA in GC.

Project description:BACKGROUND: MicroRNAs are aberrantly expressed and correlate with tumourigenesis and the progression of solid tumours. The miR-200 family determines the epithelial phenotype of cancer cells and regulates invasiveness and migration. Thus, we hypothesised that the quantitative detection of the miR-200 family as epithelial-specific microRNAs in the blood could be a useful clinical biomarker for gastric cancer (GC). METHODS: We initially validated the expression levels of miR-200a, 200b, 200c and 141 in GC cell lines (n?=?2) and blood from healthy controls (n?=?19) using real-time quantitative reverse transcription PCR (qRT-PCR). The microarray expression profiles of the miR-200 family in 160 paired samples of non-tumour gastric mucosae and GC were downloaded through ArrayExpress and analysed. MiR-200c was selected for clinical validation. The qRT-PCR prospective assessment of miR-200c was performed using 67 blood samples (52 stage I-IV GC patients and 15 controls); the area under the receiver operating characteristic curve (AUC-ROC) was estimated. The Kaplan-Meier and Breslow-Wilcoxon tests were used to assess the correlation of miR-200c with overall and progression-free survival (OS and PFS). Multivariate analyses were performed using the Cox model. RESULTS: The miR-200c blood expression levels in GC patients were significantly higher than in normal controls (p?=?0.018). The AUC-ROC was 0.715 (p?=?0.012). The sensitivity, specificity and accuracy rates of 65.4%, 100% and 73.1%, respectively, were observed. The levels of miR-200c in the blood above the cutoff defined by the ROC curve was found in 17.6% of stage I-II GC patients, 20.6% of stage III patients and 67.7% of stage IV patients (p?<?0.001). The miR-200c expression levels were not associated with clinical or pathological characteristics or recent surgical procedures. There was a correlation (p?=?0.016) with the number of lymph node metastases and the increased expression levels of miR-200c in blood were significantly associated with a poor OS (median OS, 9 vs 24?months; p?=?0.016) and PFS (median PFS, 4 vs 11?months; p?=?0.044). Multivariate analyses confirmed that the upregulation of miR-200c in the blood was associated with OS (HR?=?2.24; p?=?0.028) and PFS (HR?=?2.27; p?=?0.028), independent of clinical covariates. CONCLUSIONS: These data suggest that increased miR-200c levels are detected in the blood of gastric cancer patients. MiR-200c has the potential to be a predictor of progression and survival.

Dataset Information

Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for gastric cancer.

Publications

Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for gastric cancer.

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