RESUMO
Colorectal cancer is one of the most commonly diagnosed cancers and cancer- related death worldwide. Identification of new specific biomarkers could be helpful to detection of this malignancy. Altered plasma microRNA expression has been identified in many cancers, including colorectal cancer. The main objective of this study was to identify the circulating microRNAs with the most expression changes in colorectal cancer patients compared with neoplasm free healthy individuals. MicroRNA expression profiling was performed on plasma samples of 37 colorectal cancer patients and 8 normal subjects using microRNA microarray. Quantitative real-time reverse transcription polymerase chain reaction was used to validate the two selected altered microR NAs. Plasma samples from 61 colorectal cancer patients and 24 normal subjects were used in our validation study. In profiling study we found a panel of six plasma microRNAs with significant downregulation. MicroRNA-142-3p and microRNA-26a-5p were selected and validated by polymerase chain reaction. Our results demonstrated that expression levels of plasma microRNA-142-3p and microRNA-26a-5p were significantly downregulated in patients with colorectal cancer when compared to control group. Our findings suggest that downregulation of plasma microRNA-142-3p and microRNA-26a-5p might serve as novel noninvasive biomarkers in the diagnosis of colorectal cancer, although more studies are needed to highlight the theoretical strengths
RESUMO
Survivin, a novel inhibitor of apoptosis, is re-expressed in a vast majority of human cancers and is widely considered as a diagnostic marker of cancer. Survivin protein regulates both cell division and apoptosis. There are at least 5 sliced variants of the gene with different subcellular localization and anti-apoptotic property. We examined the expression pattern of survivin and its 2 sliced variants, survivin-delta EX 3 and survivin-2B, and their prognostic values in archival collections of formalin-fixed paraffin-embedded samples of bladder tumors. Total RNA from formalin-fixed paraffin embedded samples [51 samples from 30 patients with bladder cancer and 5-year follow-up] were extracted and analyzed by semiquantitative reverse transcriptase polymerase chain reaction technique. Tissue distribution and subcellular localization of survivin protein in tumor tissues was also examined by immunohistochemistry. The expression of survivin, survivin-delta Ex3, and surviving-2B were detected in 66.6%, 47.8%, and 54.7% of the specimens, respectively. The expression of survivin and survivin-delta Ex3 were preferentially elevated in tumours with higher grades, whereas survivin-2B expression was lower in high-grade tumors [P=.04]. A reverse correlation was observed between survivin-2B expression and high-grade tumors. Immunohistochemistry results also confirmed the nuclear localization of survivin protein within tumoral cells. We were successful in detecting the expression of survivin and its variants in formalin-fixed paraffin-embedded bladder samples. Furthermore, our results showed that overexpression of survivin and survivin-delta Ex3 in bladder tumors correlates with poor prognosis of bladder cancer. We suggest that survivin and its variants are suitable prognostic markers of bladder tumors
Assuntos
Humanos , Neoplasias da Bexiga Urinária/genética , Expressão Gênica , Biomarcadores , Prognóstico , Apoptose , RNA , Reação em Cadeia da Polimerase , Imuno-HistoquímicaRESUMO
Inhibition of apoptosis may favor the onset and progression of cancer. Survivin is an inhibitor of apoptosis that has been considered as a potential marker for diagnostic and/or prognostic of bladder cancer. The survivin protein regulates both cell division and cell death and its overexpressed in the vast majority of human cancers. In this study, the expression pattern and potential prognostic value of survivin was assessed in Fomalin-Fixed Paraffin-Embedded [FFPE] samples of bladder tumor. FFPE samples, from patients with a well-known five-year survival record, were assessed by semi-quantitative RT-PCR technique. 51 samples from 30 patients were analyzed on the basis of Survivin expression. Tissue distribution and subcellular localization of survivin protein in tumor tissues was also examined by immunohistochemistry [IHC]. The expression of survivin in 66.6% of the samples, with an increase of expression in higher grades of tumor. Furthermore, survivin was overexpressed in 2[nd] and 3[rd] recurrences of the same patients. Also, with the increased malignancy and accordingly increase expression of surviving, the overall 5-year survival rate of patients was significantly declined [P=0.036]. IHC results also localized a nuclear localization for Survivin protein in tumor tissues. In coclusion, we were able to detect the expression of survivin in FFPE samples of bladder tissues, at the level of mRNA and protein and find a correlation between the level of Survivin expression and the degree of malignancy of the tumors. Our findings introduce Survivin as a suitable prognostic marker for predicting the bladder tumors