Expression Levels of the CA9, WT1, and PRAME genes and genotyping-associated antigens for the diagnosis and prognosis of colorectal cancer

Background: Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide, and is one of the major health problems in Asia, Africa, Europe, and America. The tumor antigens recently are of interesting indicators as diagnostic and prognostic tools, The aim of the present study is to detect the expression levels of carbonic anhydrase IX (CA9), the Wilms tumor gene (WT1), and the preferentially expressed antigen in melanoma (PRAME) in the peripheral blood of CRC patients in comparison with healthy controls. Methods: A prospective case-control study of CRC patients was conducted. We included 25 newly-diagnosed CRC eligible patients and obtained peripheral blood samples of them as well as 10 blood samples from the control group. All samples were then submitted to deoxyribonucleic acid (DNA) extraction and a molecular study through real-time polymerase chain reaction (PCR). Results: The CRC group consisted of 15 (60%) female and 10 (40%) male patients with a mean age of 50.52 ± 9.8 years, while the control group included 4 (40%) female and 6 (60%) male patients with a mean age of 47.7 ± 7.9 years. The CRC group, 24 (96%) of patient samples were CA9-positive with strong statistically significant differences (p < 0.00001; sensitivity: 96%; specificity: 90%). Regarding the WT1 gene, there were 11 (44%) positive samples in the CRC group, with no statistically significant differences (p = 0.055; sensitivity: 44%; specificity: 90%). The PRAME gene was positive in 9 (36%) samples in the CRC group, with no statistically significant differences (p = 0.357; sensitivity: 36%; specificity: 80%. Among CA9 (24 patients; 96%) of patients with CRC expressed positive results, in WT1 11(91.6%) CRC patients expressed gene, and in PRAME gene, 9 patients with CRC (81.8%) expressed positive results. Conclusion: Overexpression of the CA9 gene in CRC of high sensitivity and specificity to be used as a tool to discriminate CRC from benign associate with high accuracy compare to WT1 and PRAME genes. (AU)

PRAME gene expression profile in medulloblastoma / Perfil de expressão do gene PRAME em meduloblastoma

Medulloblastoma is the most common malignant tumors of central nervous system in the childhood. The treatment is severe, harmful and, thus, has a dismal prognosis. As PRAME is present in various cancers, including meduloblastoma, and has limited expression in normal tissues, this antigen can be an ideal vaccine target for tumor immunotherapy. In order to find a potential molecular target, we investigated PRAME expression in medulloblastoma fragments and we compare the results with the clinical features of each patient. Analysis of gene expression was performed by real-time quantitative PCR from 37 tumor samples. The Mann-Whitney test was used to analysis the relationship between gene expression and clinical characteristics. Kaplan-Meier curves were used to evaluate survival. PRAME was overexpressed in 84 percent samples. But no statistical association was found between clinical features and PRAME overexpression. Despite that PRAME gene could be a strong candidate for immunotherapy since it is highly expressed in medulloblastomas.

Meduloblastoma é o tumor maligno mais comum em sistema nervoso central na infância. O tratamento é agressivo e o prognóstico é restrito. Como PRAME está presente em vários tumores, incluindo meduloblastoma, e possui baixa expressão em tecidos normais, este antígeno pode ser ideal na imunoterapia. A fim de encontrar um potencial alvo molecular, investigamos a expressão PRAME em fragmentos de meduloblastoma e comparamos os resultados com as características clínicas de cada paciente. Análise da expressão do gene foi realizada por PCR real-time quantitativo em 37 amostras de tumor. O teste de Mann-Whitney foi utilizado para análise da relação entre a expressão do gene e características clínicas e teste de Kaplan-Meier para avaliar a sobrevida. PRAME teve superexpresssão em 84 por cento amostras, mas não houve nenhuma relação estatística entre as características clínicas e superexpressão de PRAME. Apesar disso, o gene PRAME poderia ser um forte candidato para a imunoterapia, pois é altamente expresso em meduloblastomas.

Expression of PRAME gene in acute leukemia and its clinical significance compared with FLT3 gene / 白血病·淋巴瘤

Objective To investigate the expression of preferentially expressed antigen of melanoma (PRAME) gene in acute leukemia and its clinical significance.Methods PRAME mRNA levels were detected in bone marrow samples from 119 cases with acute leukemia (out of which 97 cases were acute myeloid leukemia, 22 cases were acute lymphocytic leukemia) by TaqMan based real-time quantitative PCR methods and compared it with the expression of FLT3 gene. Results PRAME mRNA was revealed in 50 of 97 AML (51.5 %), 8 of 22 ALL (36.4 %), and 5 patients were found little expression of PRAME in 11 healthy subjects and 17 non-blood disease patients. However, 17 AML, and 3 ALL patients with PRAME expression had no detectable FLT3. 9 patients with the expression of both PRAME and FLT3 genes were monitored in short follow-up. The lower level of PRAME was detected in all patients when they were in complete remission (CR) after chemotherapy. Conclusion PRAME gene was expressed in acute leukemia patients and will hopefully become a symbolic gene during the course of diagnosis and treatment in acute leukemia.

Development of PRAME in the diagnosis and treatment of children acute leukemia / 国际儿科学杂志

The gene of preferentially expressed antigen of melanoma(PRAME) is a gene marker of leukemia,which can be used to monitor the minimal residual disease,and can make us to comprehend the curative effect,prognosis,the grade of risk and can predict relapse.In addition,PRAME as a human tumour antigen,can be recognized by autologous cytolytic T lymphocytes,is a ideal target of immunotherapy in leukemia,and investigate the methylation level of PRAME gene CpG island,which can help us comprehend the relation of the mechanism of PRAME and leukemia.