Bladder cancer is a fatal disease, with high metastasis ability [17]. There are various available treatments for bladder cancer patients, including radiation therapy, immunotherapy, radical cystectomy, and postoperative instillation of chemotherapy [18, 19]. However, the clinical outcomes of the patients have not been significantly improved. The prognosis of the patients is closely correlated with the tumor stages. Early diagnosis is very important for the prognosis of bladder cancer patients. Currently, the early detection of bladder cancer mainly dependents on cystoscopy and voided urinary cytology. However, the clinical values are limited due to invasive and uncomfortable procedures, low sensitivity and high cost [20, 21]. Therefore, the novel molecular biomarkers are in urgent need for early diagnosis of bladder cancer. In this study, we aimed to explore a novel biomarker to achieve the early diagnosis of bladder cancer.
CASC2 is a novel lncRNA in human genome, and it was firstly discovered by Baldinu, P et al. in human endometrial cancer [15]. The abnormal expression of CASC2 is found in many human cancers, and it can act as a tumor suppressor [22]. For instance, Wang et al. found that in glioma tissues and cell lines the expression level of CASC2 was down-regulated [23]. The study of He et al. found the expression of CASC2 was lower in non-small cell lung cancer (NSCLC) tissues and was correlated with tumor size and tumor stage [24]. The study group of Cao et al. indicated that CASC2 expression was down-regulated in human renal cell carcinoma (RCC) tissues and cell lines [25]. The expression patterns of CASC2 showed close association with cancer progression, which might be a potential biomarker for management of cancers [26, 27]. However, the clinical significance of CASC2 has been rarely investigated in bladder cancer.
In this study, we found that the expression level of CASC2 was significantly lower in bladder cancer patients than that in healthy volunteers. Moreover, the expression of CASC2 was negatively correlated with histological grade, TNM stage, and lymph node metastasis. The down-regulation of CASC2 might contribute to malignant progression of bladder cancer. The study performed by Li et al. indicated that the bladder cancer patients with low expression of CASC2 were more likely to undergo malignant disease progression and postoperative recurrence [28]. Pei er al. reported that the enforced expression of CASC2 could remarkably inhibit cell growth, migration and invasion, and promote cell apoptosis in bladder cancer cells in vitro. CASC2 might play anti-tumor action in bladder cancer through inhibiting Wnt/β-catenin pathway [14]. Both of the published articles might explain the results obtained in our study.
Given its distinct expression profile in bladder cancer, we hypothesized that serum CASC2 might be a potential diagnostic biomarker for the cancer. Thus, ROC analysis was performed to detect the diagnostic value of CASC2 in bladder cancer patients. From the ROC curve, we could see that the CASC2 expression could discriminate between bladder cancer patients and healthy controls with the sensitivity of of 77.8%, specificity of 85.7%, and the AUC of 0.864. Serum CASC2 might be a potential non-invasive biomarker for early detection of bladder cancer. However, several limitations should be stated in current study. Firstly, the sample size was relatively small that might reduce the statistical power of our results. Second, the molecular mechanisms underlying the anti-tumor action of CASC2 in progression of bladder cancer was not explored in our study. In addition, all the individuals in control group were healthy, our results only confirmed that serum CASC2 could distinguish bladder cancer patients from the healthy individuals. Whether serum CASC2 could discriminate between bladder cancer patients and other malignancies cases remained unclear. Therefore, well-designed studies with a larger sample are required to verify and improve our conclusion.