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Upregulated expression of serum exosomal hsa_circ_0026611 is associated with lymph node metastasis and poor prognosis of esophageal squamous cell carcinoma.

ABSTRACT: Background: To identify the diagnostic and prognostic values of serum exosomal hsa_circ_0026611 in esophageal squamous cell carcinoma (ESCC). Methods: ESCC serum exosome global circRNA expression was detected using a circRNA microarray. The expression levels of candidate serum exosome circRNAs were detected by quantitative polymerase chain reaction (qRT-PCR). A receiver operating characteristic curve (ROC) was generated to confirm the diagnostic value. Survival data and their differences were observed by the Kaplan-Meier method and log-rank tests. The Cox regression analysis was employed to identify prognostic factors. Results: The expression levels of serum exosomal has_circ_0026611 in ESCC with lymph node metastasis were significantly higher than those in ESCC without lymph node metastasis (P =0.001). In addition, serum exosomal hsa_circ_0026611 expression could be used as a significant parameter to discriminate between non-lymph node-metastatic and lymph node-metastatic ESCC with an area under curve (AUC) of 0.724 (95% CI: 0.604~0.865). The multivariate Cox regression analysis indicated that survival was poor in patients with high serum exosomal hsa_circ_0026611 expression levels compared to those with low serum exosomal hsa_circ_0026611 levels (for OS, HR [95% CI]: 3.79 [1.27, 11.29], for DFS, HR [95% CI]: 2.77 [1.06, 7.22]). Conclusion: Serum exosomal hsa_circ_0026611 expression is significantly upregulated in ESCC with lymph node metastasis and is a predictor of ESCC prognosis.

SUBMITTER: Liu S

PROVIDER: S-EPMC7778553 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeMolecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methodsThis study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan-Meier analysis with a log-rank test was used for the survival analysis.ResultsLAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.ConclusionThese findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.

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Upregulated expression of serum exosomal hsa_circ_0026611 is associated with lymph node metastasis and poor prognosis of esophageal squamous cell carcinoma.

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