Bladder cancer is a heterogeneous disease with unpredictable clinical course, representing a leading cancer-related deaths . At present, there are several major risk factors identified in bladder cancer, such as cigarette smoking, chronic infection by Schistosoma haematobium, and exposure to the carcinogens [16, 17]. Early diagnosis and close monitoring are key for clinical outcomes of patients with bladder cancer. Unfortunately, there are no recommended biomarkers for bladder cancer in routine clinical application until now . In current study, we confirmed that the expression profiles of urine MACC1 were significantly different between bladder cancer patients and non-malignant individuals. Urine MACC1 might be a potential diagnostic biomarker for bladder cancer.
MACC1 encodes a protein containing four domains: ZU5, SH3 and two C-terminal death domains . Growing evidences have demonstrated that the over-expression of MACC1 may contribute to malignant tumor progression through enhancing cell proliferation, migration and invasion [8, 20–22]. The expression pattern of MACC1 in human fluids may have the possible to serve as a biomarker for early diagnosis and prognosis evaluation in several types of human cancers. For instance, Ashkorab et al. reported that MACC1 transcripts were obviously increased in plasma samples of colon adenoma patients compared with normal patients. Moreover, plasma MACC1 could distinguish the colon adenoma patients from healthy individuals . Tan et al. showed that serum MACC1 was highly expressed in breast cancer patients, and it might be a reliable biomarker for early diagnosis and prognosis evaluation in breast cancer patients . A study carried out by Wang et al., reported that plasma MACC1 expression exhibited significantly increased in non-small cell lung cancer patients, and might be a promising non-invasive factor for diagnosis and prognosis of the disease . Taken together, the expression of MACC1 in human fluids shows specific to cancer, which may be employed as biomarker for diagnosis and monitoring of cancer. However, the clinical significance of urine MACC1 in bladder cancer was rarely reported.
In this study, urine MACC1 mRNA expression was examined in bladder cancer patients and controls using qRT-PCR method. The expression of MACC1 was significantly increased in urine samples of bladder cancer patients in comparison to controls. The result was in line with the previous study reported by Xu et al., revealing that MACC1 mRNA levels were up-regulated in human urothelial carcinoma . In addition, we estimated the association of urine MACC1 expression with clinicopathological parameters of bladder cancer patients. The abnormal MACC1 expression in urine samples was remarkably associated with tumor differentiation, tumor stage, lymph node metastasis, and distant metastasis. The bladder cancer patients with high expression of MACC1 were more likely to undergo malignant disease progression. The in vitro experiments carried out by Xu et al. suggested that MACC1 could regulate the biological behaviors of human bladder urothelial carcinoma cell line T24 . Over-expression of MACC1 might contribute to progression of bladder cancer through enhancing the malignant biological behaviors of cancer cells.
Given the different levels of urine MACC1 in bladder cancer cases and healthy individuals, we hypothesized that urine MACC1 might be a potential diagnostic biomarker for bladder cancer. ROC curves were plotted to estimate the diagnostic performance of urine MACC1 in bladder cancer. Urine MACC1 could distinguish bladder cancer patients from the non-malignant controls with high sensitivity and specificity. Urine MACC1 might act as a valid and reliable biomarker for early screening of patients suffering from bladder cancer.
This study had certain limitations. Firstly, the number of patients recruited in the study was relatively small, and further studies with a large scale number of patients are required to confirm our findings. Secondly, the patients corrected in our study all came from one hospital that might cause bias to our results. In addition, the molecular mechanisms underlying the oncogenic function of MACC1 remained poorly known. Further in vitro and in vivo experiments are required to address the issues. Therefore, multicenteric studies should be considered to verify the value of MACC1 as a diagnostic biomarker for bladder cancer.