OBJECTIVE Numerous microRNAs (miRNAs) are deregulatedin human cancers. The experimental evidence supports thatmiRNAs plays a role in the initiation and progression of humanmalignancies.The present study was undertaken...OBJECTIVE Numerous microRNAs (miRNAs) are deregulatedin human cancers. The experimental evidence supports thatmiRNAs plays a role in the initiation and progression of humanmalignancies.The present study was undertaken to evaluatethe differential expression of 6 miRNAs as biomarker for earlydetection of prostate cancer, and then to determine whether theexpression profiling of these miRNAs could predict the prognosisof prostate cancer.METHODS The expression profilings of these 6 miRNAs wereinvestigated using the method of locked nucleic acid (LNA)-modified oligonucleotide in situ hybridization (ISH). And thetechnology of tissue microarray (TMA) was employed using theformalin-fixed, paraffin-embedd (FFPE) specimens taken from52 patients with prostate carcinoma (PCa) and 38 patients withbenign prostatic hyperplasia (BPH).RESULTS The rates of positive expression for 6 miRNAs (miR-15b, miR-16, let-7g, miR- 96,miR-182 and miR-183) were 26.92%,15.38%, 15.38%, 67.31%, 61.54% and 71.15% in the specimens ofprostate cancer, and 57.89%, 76.32%, 68.42%, 44.74%, 31.58%,47.37% in the tissues of benign prostatic hyperplasia, respectively.The expressions of all 6 miRNAs between the prostate cancer andbenign prostatic hyperplasia tissues were significantly different(P < 0.05). The positive rate of these 6 miRNAs was significantlyrelated to the Gleason Grading of prostate cancer (P < 0.01). Therewas no significant correlation between the expression of thesemiRNAs and age and the concentration of serum PSA of thepatient (P >0.05). We also found that the expression of miR-15b,miR-96 and miR-182 correlated with clinical stages of tumor (P <0.05). The expression of miR-96 correlated with lobus prostatae oftumor invasion (P < 0.01), but the expressions of the remaining fivemiRNAs were not correlated with that (P >0.05). In addition, theexpression of miR-15b was negatively related to that of miR-96,miR-182 and miR-183, respectively (P < 0.01, r < 0.00).There wasa positive correlation among the expressions of miR-96, miR-182and miR-183 in prostate cancer (P < 0.01, r >0.00). The expressionof miR-16 was positively related to that of miR-let-7g (P < 0.01, r >0.00).CONCLUSION The results suggest that miRNA expressionprofiling could have relevance to the biological and clinicalbehavior of prostate cancer,and they might be importantbiomarkers for early detection and prognostic assessment ofprostate cancer.展开更多
Prostate cancer （PCa） incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men＇s death worldwide. Changes in many ce...Prostate cancer （PCa） incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men＇s death worldwide. Changes in many cell signaling pathways have a predominant role in the onset, development, and progression of the disease. These include prominent pathways involved in the growth, apoptosis, and angiogenesis of the normal prostate gland, such as an- drogen and estrogen signaling, and other growth factor signaling pathways. Understanding the foundations of PCa is leading to the discovery of key molecules that could be used to improve patient management. The ideal scenario would be to have a panel of molecules, preferably detectable in body fluids, that are specific and sensitive biomarkers for PCa In the early stages, androgen deprivation is the gold standard therapy. However, as the cancer progresses, it even- tually becomes independent of androgens, and hormonal therapy fails. For this reason, androgen-independent PCa is still a major therapeutic challenge. By disrupting specific protein interactions or manipulating the expression of some key molecules, it might be possible to regulate tumor growth and metastasis formation, avoiding the systemic side effects of current therapies. Clinical trials are already underway to assess the efficacy of molecules specially designed to target key proteins or protein interactions. In this review, we address that recent progress made towards under- standing PCa development and the molecular pathways underlying this pathology. We also discuss relevant molecular markers for the management of PCa and new therapeutic challenges.展开更多
文摘OBJECTIVE Numerous microRNAs (miRNAs) are deregulatedin human cancers. The experimental evidence supports thatmiRNAs plays a role in the initiation and progression of humanmalignancies.The present study was undertaken to evaluatethe differential expression of 6 miRNAs as biomarker for earlydetection of prostate cancer, and then to determine whether theexpression profiling of these miRNAs could predict the prognosisof prostate cancer.METHODS The expression profilings of these 6 miRNAs wereinvestigated using the method of locked nucleic acid (LNA)-modified oligonucleotide in situ hybridization (ISH). And thetechnology of tissue microarray (TMA) was employed using theformalin-fixed, paraffin-embedd (FFPE) specimens taken from52 patients with prostate carcinoma (PCa) and 38 patients withbenign prostatic hyperplasia (BPH).RESULTS The rates of positive expression for 6 miRNAs (miR-15b, miR-16, let-7g, miR- 96,miR-182 and miR-183) were 26.92%,15.38%, 15.38%, 67.31%, 61.54% and 71.15% in the specimens ofprostate cancer, and 57.89%, 76.32%, 68.42%, 44.74%, 31.58%,47.37% in the tissues of benign prostatic hyperplasia, respectively.The expressions of all 6 miRNAs between the prostate cancer andbenign prostatic hyperplasia tissues were significantly different(P < 0.05). The positive rate of these 6 miRNAs was significantlyrelated to the Gleason Grading of prostate cancer (P < 0.01). Therewas no significant correlation between the expression of thesemiRNAs and age and the concentration of serum PSA of thepatient (P >0.05). We also found that the expression of miR-15b,miR-96 and miR-182 correlated with clinical stages of tumor (P <0.05). The expression of miR-96 correlated with lobus prostatae oftumor invasion (P < 0.01), but the expressions of the remaining fivemiRNAs were not correlated with that (P >0.05). In addition, theexpression of miR-15b was negatively related to that of miR-96,miR-182 and miR-183, respectively (P < 0.01, r < 0.00).There wasa positive correlation among the expressions of miR-96, miR-182and miR-183 in prostate cancer (P < 0.01, r >0.00). The expressionof miR-16 was positively related to that of miR-let-7g (P < 0.01, r >0.00).CONCLUSION The results suggest that miRNA expressionprofiling could have relevance to the biological and clinicalbehavior of prostate cancer,and they might be importantbiomarkers for early detection and prognostic assessment ofprostate cancer.
基金Project supported by Fundao para a Ciência e Tecnologia(FCT)(PTDC/QUI-BIQ/118492/2010)Fundo Europeu de Desenvol-vimento Regional(FEDER)(FCOMP-01-0124-FEDER-020895),Portugal
文摘Prostate cancer （PCa） incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men＇s death worldwide. Changes in many cell signaling pathways have a predominant role in the onset, development, and progression of the disease. These include prominent pathways involved in the growth, apoptosis, and angiogenesis of the normal prostate gland, such as an- drogen and estrogen signaling, and other growth factor signaling pathways. Understanding the foundations of PCa is leading to the discovery of key molecules that could be used to improve patient management. The ideal scenario would be to have a panel of molecules, preferably detectable in body fluids, that are specific and sensitive biomarkers for PCa In the early stages, androgen deprivation is the gold standard therapy. However, as the cancer progresses, it even- tually becomes independent of androgens, and hormonal therapy fails. For this reason, androgen-independent PCa is still a major therapeutic challenge. By disrupting specific protein interactions or manipulating the expression of some key molecules, it might be possible to regulate tumor growth and metastasis formation, avoiding the systemic side effects of current therapies. Clinical trials are already underway to assess the efficacy of molecules specially designed to target key proteins or protein interactions. In this review, we address that recent progress made towards under- standing PCa development and the molecular pathways underlying this pathology. We also discuss relevant molecular markers for the management of PCa and new therapeutic challenges.
