| BackgroundBladder cancer is one of the most common cancers in the Western world. The most common subtype of bladder cancer is of the transitional (urothelial) cell type. In America,90%of patients suffering from Bladder cancer were exactly with Bladder urothelial cancer.80%of patients with urothelial bladder cancer suffer from recurrence within1or2years of the initial treatment. Fifteen-20%of bladder tumours were muscle-invasive.50%of these patients die from metastatic disease despite radical cystectomy (RC) and systemic therapy,Many bladder cancers are detected on evaluation for gross hematuria. At diagnosis, three quarters of these tumors are non-muscle invasive. A screening program, particularly in highrisk populations such as heavy smokers or those with occupational exposure, would identify tumors earlier in patients presenting with gross hematuria, thus decreasing the rate of tumor invasion or metastasis.When it comes to the diagnosis and monitoring of bladder cancer, the gold standard is cystoscopy and urine cytology. However, cystoscopy is invasive and expensive, while cytology is not that sensitive and is of poor interobserver reproducibility. The researchers and clinical workers could accurately identify the early stage of cancer progression through evaluating the biological, morphological and clinical alterations in malignant and pre-malignant lesions, all of that do enhance the cancer treatment. In recent years, in the study of biomarkers associated with the molecular changes occurring during the development and progression of urothelial carcinoma, considerable advances have been made. Information generated by such biomarkers may enable intervention at an earlier stage of the disease than under usual clinical diagnostic conditions. It may also allow the monitoring of a therapeutic action on disease progression in addition to the classical signs and symptoms. Through the incorporation of some validated biomarkers, the clinical workers can expect better clinical study designs which improve the patients’ prospects by reducing morbidity and mortality while cutting the costs of every bladder cancer patient from diagnosis to death. Therefore, not only the patients but also the healthcare systems would benefit from the use of biomarkers.Med-19is an integral part of the central body in mediatior, which can get activated transcription factors and RNA Pol Ⅱ linked. At the very first, Med-19was discovered in the nucleus. The researchers concluded that Med-19might be a regulatory factor. Later studies confirmed that as part of intermediary intermediary, Med-19complex has a fundamental role for the binding and activation of RNA Pol Ⅱ. In the absence of Med-19, mediator affinity for RNA Pol Ⅱ decreased. As a regulator of gene expression activators of transcription, Med-19may involve in the development of tumors. Several studies have demonstrated that Med-19may be related with bladder cancer, prostate cancer, hepatocellular cancer, breast cancer cells, gastric cancer and the proliferation of a relationship tongue. This study explores Med-19gene mRNA and protein expression in the bladder cancer, and find out that Med-19expression increases in the bladder cancer tissue, moreover, the expression of the Med-19protein correlated with the bladder cancer diameter, clinical stage, histological grade, lymph node metastasis and early recurrence.MethodsTotally64bladder tumor specimens from patients who underwent open surgery and transurethral resection in our hospital among January2010～June2012were involved in the research. All the specimens were histologically diagnosed as bladder cancer. Among them,32were from males while the other32were from females. The patients involed in the research aged between28to78, the mean age was54.3±2.5years. According to the World Health Organisation grading in2004,38cases were low-grade tumors while the other26cases were high-grade tumors. According to the TNM classification of urinary bladder cancer approved by the Union International Contre le Cancer in2002,36cases were non-muscle invasive tumors, and the other28 cases were muscle invasive tumors.38cases were onset tumors,26cases were recurrent tumors.39cases were without lymph node metastasis while the other25cases were with lymph node metastasis.20cases of normal controls were normal bladder mucosa taken from patients suffering a prostate surgery. All specimens were devided into2parts, frozen in liquid nitrogen for10min and then stored at-70℃. This study was approved by the ethic committee of our hospital, patients enrolled in the study have the right of informed consent.The Med-19mRNA/GAPDH mRNA relative expression ratio of bladder cancer tissue and normal bladder mucosa was investigated using RT-PCR analysis. Using Western-blot, the Med-19protein expression was detected in bladder cancer tissue and normal bladder mucosa. Spearman correlation analysis indicated that the relevance of Med-19mRNA with Med-19protein expression in bladder cancer, and the relevance of MED-19protein expression with the diameter of bladder cancer, clinical stage, histological grade, lymph node metastasis and early recurrence the correlation.ResultsWestern-blot analysis showed that among the64tumor samples, Med-19protein expressed in52cases, and the mean expression level was0.628±0.135. In20cases of normal gastric mucosa, Med-19protein expression was detected only in two cases, and the mean expression level was0.086±0.028. The difference between the tumor sample group and the normal sample group was statistically significant (t=18.55, P=0.000).RT-PCR analysis showed that in64cases, Med-19mRNA expression was detected in56cases, the mean expression level was0.874±0.083. Med-19mRNA expression was detected in only1case of normal mucosa specimens in20cases, the expression level was0.104±0.041. Med-19mRNA expression in56cases of tumor specimens was significantly higher than that in normal mucosa specimens (t=20.14, P=0.000).In64cases of bladder cancer specimens,52cases (81.3%) exists Med-19protein expression,56cases (87.5%) showed Med-19mRNA expression. In the bladder cancer tissue with positive Med-19mRNA expression, positive Med-19protein expression rate was85.7%(48/56). In the bladder cancer tissue with positive Med-19protein expression, positive Med-19mRNA expression rate was92.3%(48/52). Med-19mRNA expression and Med-19protein expression in bladder carcinoma was correlated with each other (r=0.892, χ2=13.43, P<0.001).Med-19protein expression levels in different groups of bladder cancer cases are shown in Table2. Med-19protein expression in bladder cancer tissue was not correlated with the gender and age (P>0.05). In high-grade tumor group, muscle invasive tumor group, group with lymph node metastasis, group with tumor recurrence, group with tumor diameter>3cm, Med-19protein expression level was significantly higher than that in the low-grade group, non-muscle invasive tumor group, group without lymph node metastasis, tumor onset group and group with tumor diameter of<3cm, respectly (P<0.05).Conclusions1. Med-19mRNA expression levels were significantly increased in bladder cancer tissue compared to normal mucosa. Med-19protein expression levels were also significantly increased in bladder cancer tissue compared to normal mucosa. And the Med-19mRNA expression levels and the Med-19protein expression levels was correlated with each other. Med-19may involve in the development of bladder cancer.2. Med-19protein expression was correlated with the biological behavior of bladder cancer including the diameter of bladder cancer, clinical stage, histological grade, lymph node metastasis and recurrence in early. Med-19may be used as early diagnosis biomarkers or clinical stage molecular markers of bladder cancer. |
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