Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer-host cross talk. The aim of our study was to illustrate the clinical significance of the lncRNA CRNDE-h in exosomes purified from the serum of patients with colorectal cancer (CRC). The study was divided into four parts: (1) The exosome isolated methods and lncRNA detected methods which accurately and reproducibly measure CRC-related exosomal CRNDE-h in serum were optimized in preliminary pilot stage; (2) The stability of exosomal CRNDE-h was evaluated systematically; (3) The origin of exosomal CRNDE-h was explorated in vitro and in vivo; (4) The diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468 patients. In pilot study, our results indicated that exosomal CRNDE-h was detectable and stable in serum of CRC patients, and derived from tumor cells. Then, the increased expression of exosomal CRNDE-h was successfully validated in 148 CRC patients when compared with colorectal benign disease patients and healthy donors. Exosomal CRNDE-h level significantly correlated with CRC regional lymph node metastasis (P = 0.019) and distant metastasis (P = 0.003). Moreover, at the cut-off value of 0.020 exosomal CRNDE-h level of serum, the area under ROC curve distinguishing CRC from colorectal benign disease patients and healthy donors was 0.892, with 70.3% sensitivity and 94.4% specificity, which was superior to carcinoembryogenic antigen. In addition, high exosomal CRNDE-h level has a lower overall survival rates than that for low groups (34.6% vs. 68.2%, P < 0.001). In conclusion, detection of lncRNA CRNDE-h in exosome shed a light on utilizing exosomal CRNDE-h as a noninvasive serum-based tumor marker for diagnosis and prognosis of CRC.
Preoperative prediction of lymph node (LN) metastasis is accepted as a crucial independent risk factor for treatment decision-making for esophageal squamous cell carcinoma (ESCC) patients. Our study aimed to establish a non-invasive nomogram to identify LN metastasis preoperatively in ESCC patients. Construction of the nomogram involved three sequential phases with independent patient cohorts. In the discovery phase ( N = 20), LN metastasis-associated microRNAs (miRNAs) were selected from next-generation sequencing (NGS) assay of human ESCC serum exosome samples. In the training phase ( N = 178), a nomogram that incorporated exosomal miRNA model and clinicopathologic was developed by multivariate logistic regression analysis to preoperatively predict LN status. In the validation phase ( n = 188), we validated the predicted nomogram's calibration, discrimination, and clinical usefulness. Four differently expressed miRNAs (chr 8-23234-3p, chr 1-17695-5p, chr 8-2743-5p, and miR-432-5p) were tested and selected in the serum exosome samples from ESCC patients who have or do not have LN metastasis. Subsequently, an optimized four-exosomal miRNA model was constructed and validated in the clinical samples, which could effectively identify ESCC patients with LN metastasis, and was significantly superior to preoperative computed tomography (CT) report. In addition, a clinical nomogram consisting of the four-exosomal miRNA model and CT report was established in training cohort, which showed high predictive value in both training and validation cohorts [area under the receiver operating characteristic curve (AUC): 0.880 and 0.869, respectively]. The Hosmer–Lemeshow test and decision curve analysis implied the nomogram's clinical applicability. Our novel non-invasive nomogram is a robust prediction tool with promising clinical potential for preoperative LN metastasis prediction of ESCC patients, especially in T1 stage.
Pulmonary fibrosis is a severe respiratory disease characterized by the aggregation of extracellular matrix components and inflammation‑associated injury. Studies have suggested that long non‑coding RNAs (lncRNA) may serve a role in the pathophysiological processes of pulmonary fibrosis. However, the potential molecular mechanisms involving the lncRNA, prostate cancer‑associated transcript 29 (lncRNAPCAT29) in the progression of pulmonary fibrosis are yet to be determined. In the present study, the role of lncRNAPCAT29 and the potential signaling mechanism in pulmonary fibrosis progression was investigated. Reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry revealed that the expression levels of lncRNAPCAT29 were downregulated within interstitial lung cells from mice with silica‑induced pulmonary fibrosis. Transfection with lncRNAPCAT29 was associated with upregulated expression of microRNA (miRNA)‑221 and downregulated expression of transforming growth factor‑β1 (TGF‑β1); reduced inflammation and fibrotic progression was also associated with lncRNAPCAT29 transfection. TGF‑β1 expression levels were inhibited within pulmonary fibroblasts due to lncRNAPCAT29 expression; NEDD4 binding protein 2 and Plexin‑A4 expression levels were also suppressed. Analysis of the potential mechanism underlying silica‑induced pulmonary fibrosis revealed that the expression levels of RAS protein activator like 1 (RASAL1) and extracellular signal‑regulated kinases 1/2 (ERK1/2) were suppressed due to lncRNAPCAT29 expression. The results of the present study demonstrated that lncRNAPCAT29 induced miRNA‑221 upregulation and TGF‑β1 downregulation. These observations were associated with reduced inflammation and progression of silica‑induced pulmonary fibrosis via the TGF‑β1‑regulated RASAL1/ERK1/2 signaling pathway, which may serve as a potential target for the treatment of pulmonary fibrosis.
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