Decreased miR-503 expression in gastric cancer is inversely correlated with serum carcinoembryonic antigen and acts as a potential prognostic and diagnostic biomarker

Wu, Daoyi; Cao, Gaojian; Huang, Zhenfeng; Jin, Kai; Hu, Haowei; Yu, Jie; Zeng, Yu

doi:10.2147/ott.s114303

Cited by 17 publications

(10 citation statements)

References 28 publications

(26 reference statements)

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“…In this study, the median value of CEA in the GC group was 2.74 (1.685-5.62) ng/ ml, which was higher than the 1.525 (1.09-2.385) ng/ml in the benign control, and the difference was statistically significant. When we used the clinically recommended 3.4 ng/ml as the cut-off value, the sensitivity was 0.409, the specificity was 0.942, and the AUC was 0.676, which are consistent with previous research [23,24]. Therefore, we believe that the level of CEA can help diagnose GC.…”

Section: Discussionsupporting

confidence: 88%

The significance of preoperative serum carcinoembryonic antigen levels in the prediction of lymph node metastasis and prognosis in locally advanced gastric cancer: a retrospective analysis

et al. 2020

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Background: In this study, we aimed to investigate the preoperative serum carcinoembryonic antigen (CEA) in the diagnosis of positive lymph node metastasis (LNM), and to evaluated the relationship between CEA and survival in patients with locally advanced gastric cancer (LAGC). Methods: The significance of the preoperative serum CEA level for the diagnose of LAGC and prediction of LNM was determined using the receiver operating characteristic (ROC) curve. The areas under the ROC of CEA were compared with those of other tumor markers or imaging examination including CT and MRI. Logistic regression was utilized to identify the risk factors predicting positive LNM. Independent prognosis factors were evaluated using univariate and multivariate COX regression analyses. Results:The ROC curves showed that the AUCs of CEA, CA199, and CA125 for diagnosing LAGC were 0.727, 0.594, and 0.566. When used to predict LNM, the AUC of CEA, CA199 and CA125 were 0.696, 0.531, and 0.588. Logistic regression analysis demonstrated that preoperative serum CEA were significantly associated with positive LNM. On combining imaging examination with CEA, the sensitivity and specificity were 85.3 and 79.4%, respectively, with the AUC equal to 0.853. The combination of CEA and imaging examination preformed the highest levels of AUC and sensitivity for diagnosing LNM, which is significantly higher than using either of them alone. Although patients with abnormal CEA have a poor prognosis, two models of multivariate analysis showed that CEA was not the independent prognosis factor for survival.Conclusions: CEA can be used to diagnose gastric cancer and determine whether it has LNM. Moreover, combined with CEA could improve the diagnostic sensitivity of imaging examination for lymph node involvement.

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Section: Discussionsupporting

confidence: 88%

The significance of preoperative serum carcinoembryonic antigen levels in the prediction of lymph node metastasis and prognosis in locally advanced gastric cancer: a retrospective analysis

et al. 2020

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“…mir-503 is a member of the miR-16 family and has been reported to be associated with carcinogenesis; its aberrant expression has been observed in multiple tumors ( 31 , 32 ). While certain studies have observed that miR-503 is downregulated in several types of cancer, such as oral cancer, hepatocellular carcinoma, non-small cell lung cancer and endometrioid endometrial cancer ( 32 – 35 ), it has been observed that miR-503 expression is upregulated in adrenocortical carcinoma, parathyroid carcinoma and retinoblastoma ( 36 – 38 ).…”

Section: Discussionmentioning

confidence: 99%

miR-503 suppresses the proliferation and metastasis of esophageal squamous cell carcinoma by triggering autophagy via PKA/mTOR signaling

Gao

et al. 2018

Int J Oncol

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MicroRNA (miR)-503 is involved in the regulation of the malignant phenotype in multiple tumor types, and has been proven to be a novel diagnostic and therapeutic target; however, its function and mechanisms of action have not yet been fully elucidated in esophageal squamous cell carcinoma (ESCC). In the current study, we detected miR-503 expression by RT-qPCR and found that miR-503 expression was increased in ESCC, but negatively correlated with lymph node metastasis, TNM stage and tumor differentiation. Functionally, we confirmed that miR-503 inhibited the proliferation and metastasis of ESCC cells by triggering cellular autophagy. Mechanistically, we confirmed that miR-503 exerted its biological effects by targeting protein kinase CAMP-activated catalytic subunit alpha (PRKACA) in ESCC by dual luciferase reporter assay. Moreover, miR-503 was found to trigger autophagy in ESCC cells through the protein kinase A (PKA)/mammalian target of rapamycin (mTOR) pathway. Taken together, our results demonstrate that miR-503 suppresses the proliferation and metastasis of ESCC via the activation of autophagy, mediated by the PKA/mTOR signaling pathway.

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“…The expression of miR-503 inhibits the migration and invasion of hepatocellular carcinoma cells in vitro [35]. In addition, the down-regulation of miR-503 is associated with poor clinical outcome and inversely associated with the level of carcinoembryonic antigen in gastric cancer [36]. Whereas, miR-503 overexpression is identified in ALDH1-positive chemoresistant ovarian cancer cells [19], ALDH1(+) ovarian cancer cells comprise 0.4–4.0% of primary cancer cells [19].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-503-5p Inhibits the CD97-Mediated JAK2/STAT3 Pathway in Metastatic or Paclitaxel-Resistant Ovarian Cancer Cells

Park

Kim

2019

Neoplasia

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CD97 shows a strong relationship with metastasis and poor clinical outcome in various tumors, including ovarian cancer. The expression of CD97 in metastatic ovarian cancer cells was higher than that in primary ovarian cancer cells. Mature miRNAs are frequently de-regulated in cancer and incorporated into a specific mRNA, leading to post-transcriptional silencing. In this study, we investigated whether the miR-503-5p targeting of the CD97 3′-untranslated region (3′-UTR) contributes to ovarian cancer metastasis as well as the underlying mechanism regulating cancer progression. In LPS-stimulated or paclitaxel-resistant ovarian cancer cells, stimulation with recombinant human CD55 (rhCD55) of CD97 in ovarian cancer cells activated NF-κB-dependent miR-503-5p down-regulation and the JAK2/STAT3 pathway, consequently promoting the migratory and invasive capacity. Furthermore, restoration of miR-503-5p by transfection with mimics or NF-κB inhibitor efficiently blocked CD97 expression and the downstream JAK2/STAT3 signaling pathway. Target inhibition of JAK with siRNA also impaired colony formation and metastasis of LPS-stimulated and paclitaxel-resistant ovarian cancer cells. Taken together, these results suggest that high CD97 expression, which is controlled through the NF-κB/miR-503-5p signaling pathway, plays an important role in the invasive activity of metastatic and drug-resistant ovarian cancer cells by activating the JAK2/STAT3 pathway.

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Decreased miR-503 expression in gastric cancer is inversely correlated with serum carcinoembryonic antigen and acts as a potential prognostic and diagnostic biomarker

Cited by 17 publications

References 28 publications

The significance of preoperative serum carcinoembryonic antigen levels in the prediction of lymph node metastasis and prognosis in locally advanced gastric cancer: a retrospective analysis

The significance of preoperative serum carcinoembryonic antigen levels in the prediction of lymph node metastasis and prognosis in locally advanced gastric cancer: a retrospective analysis

miR-503 suppresses the proliferation and metastasis of esophageal squamous cell carcinoma by triggering autophagy via PKA/mTOR signaling

MicroRNA-503-5p Inhibits the CD97-Mediated JAK2/STAT3 Pathway in Metastatic or Paclitaxel-Resistant Ovarian Cancer Cells

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