CD9 predicts ETV6-RUNX1 in childhood B-cell precursor acute lymphoblastic leukemia

ABSTRACT Introduction: The ETV6-RUNX1 is a fusion gene associated with a good outcome in B-cell precursor lymphoblastic leukemia. Objective: This study aimed to re-evaluate the CD9 cellular expression by flow cytometry (FC) as a possible tool to predict the presence of ETV6-RUNX1. Method: Childhood B-cell precursor lymphoblastic leukemia cases were included (n = 186). The percentage of CD9-labeled cells and the median fluorescence intensity ratio were used for correlation with the molecular tests. Receiver Operating Characteristic curves were performed to determine the likelihood of the CD9 expression predicting ETV6-RUNX1. Results: The ETV6-RUNX1 was found in 44/186 (23.6%) cases. Data analysis revealed that the best cutoff for CD9 percentage was 64%, with an accuracy of 0.84, whereas the best cutoff for CD9 median fluorescence intensity ratio was 12.52, with an accuracy of 0.80. A strong association was observed between the level of CD9 expression and the presence of ETV6-RUNX1. Conclusion: These data confirm that the CD9 expression could be used for risk stratification in clinical practice.

CD9 Expression in Colorectal Carcinomas and Its Prognostic Significance

BACKGROUND: CD9, a member of the tetraspanin superfamily, is a tumor suppressor in many malignancies. The aim of this study was to evaluate the immunohistochemical expression of CD9 in colorectal carcinomas (CRCs) and determine clinicopathological and prognostic significance of its expression. METHODS: The CD9 expression status of 305 CRCs was evaluated using a semi-quantitative scoring system in tumor cells (T-CD9) and immune cells (I-CD9) by classifying the results as high and low expression. RESULTS: High T-CD9 (T-CD9 [+]) expression was detected in 175 samples (57.6%) and high I-CD9 (I-CD9 [+]) expression was detected in 265 samples (86.9%). Using Kaplan-Meier survival analysis, the T-CD9 (+) group showed a tendency for better disease-free survival (DFS) (p = .057). In left-sided tumors, DFS was significantly longer in the T-CD9 (+) group (p = .021) but no statistical significance was observed with right-sided tumors (p = .453). I-CD9 (+) CRCs significantly correlated with well/moderately differentiation (p = .014). In Kaplan-Meier analysis, the I-CD9 (+) group had a tendency towards worse DFS compared to the I-CD9 (–) group (p = .156). In combined survival analysis of T-CD9 and I-CD9, we found that the longest DFS was among patients in the T-CD9 (+)/I-CD9 (–) group, whereas the T-CD9 (–)/I-CD9 (+) group showed the shortest DFS (p = .054). CONCLUSIONS: High expression of T-CD9 was associated with a favorable DFS, especially in left-sided CRCs. Combined evaluation of T-CD9 and I-CD9 is required to determine the comprehensive prognostic effect of CD9 in CRCs.

Social network of family caregivers of disabled and dependent patients / Red social de cuidadores familiares de pacientes con discapacidad y dependencia / Rede social de cuidadores familiares de pacientes com incapacidades e dependência

Cross-sectional study that used the Social Network Index and the genogram to assess the social network of 110 family caregivers of dependent patients attended by a Home Care Service in São Paulo, Brazil. Data were analyzed using the test U of Mann-Whitney, Kruskal-Wallis and Spearman correlation. Results were considered statistically significant when p<0,05. Few caregivers participated in activities outside the home and the average number of people they had a bond was 4,4 relatives and 3,6 friends. Caregivers who reported pain and those who had a partner had higher average number of relatives who to trust. The average number of friends was higher in the group that reported use of medication for depression. Total and per capita incomes correlated with the social network. It was found that family members are the primary caregiver’s social network.



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Estudio transversal que utiliza el Índice de la Red Social y el genograma para evaluar la red social de los 110 cuidadores familiares de enfermos dependientes atendidos por un servicio de cuidados en el hogar, en São Paulo. Los datos fueron analizados por las pruebas de Mann-Whitney, Kruskal-Wallis y la correlación de Spearman. Los resultados se consideraron estadísticamente significativos cuando p<0,05. Pocos cuidadores participaban en actividades fuera del hogar y el número promedio de personas con las cuales tenían vínculo fueran 4,4 personas de la familia y 3,6 amigos. Los que informaron dolor en el cuerpo y los que tenían una pareja tenían mayor número medio de familiares en que confiar. El número medio de amigos fue mayor en el grupo que informó el uso de medicación para la depresión. Los ingresos totales y per cápita se correlacionaron con la red social. Se encontró que los miembros de la familia son la principal red social del cuidador.

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Objetivo Avaliar a rede social de 110 cuidadores familiares de pacientes dependentes atendidos por um Serviço de Assistência Domiciliária no município de São Paulo. Método Estudo transversal, que utilizou o Social Network Index e o genograma. Os dados foram analisados pelos testes U de Mann-Whitney, Kruskal-Wallis e correlação de Spearman. Foram considerados estatisticamente significantes quando p <0,05. Resultados Poucos cuidadores participavam de atividades extradomiciliares e o número médio de pessoas com quem mantinham vínculo era de 4,4 familiares e 3,6 amigos. Cuidadores que referiram dor no corpo e aqueles que possuíam companheiro apresentaram maior número médio de parentes em quem confiar. A média de amigos foi superior no grupo que referiu uso de medicamentos para depressão. As rendas total e per capita mostraram correlação com a rede social. Conclusão Verificou-se que os familiares são a principal rede social do cuidador. .

Tetraspanin CD9 modulates ADAM17-mediated shedding of LR11 in leukocytes

LR11, also known as SorLA or SORL1, is a type-I membrane protein from which a large extracellular part, soluble LR11 (sLR11), is released by proteolytic shedding on cleavage with a disintegrin and metalloproteinase 17 (ADAM17). A shedding mechanism is presumed to have a key role in the functions of LR11, but the evidence for this has not yet been demonstrated. Tetraspanin CD9 has been recently shown to regulate the ADAM17-mediated shedding of tumor necrosis factor-alpha and intercellular adhesion molecule-1 on the cell surface. Here, we investigated the role of CD9 on the shedding of LR11 in leukocytes. LR11 was not expressed in THP-1 monocytes, but it was expressed and released in phorbol 12-myristate 13-acetate (PMA)-induced THP-1 macrophages (PMA/THP-1). Confocal microscopy showed colocalization of LR11 and CD9 proteins on the cell surface of PMA/THP-1. Ectopic neo-expression of CD9 in CCRF-SB cells, which are LR11-positive and CD9-negative, reduced the amount of sLR11 released from the cells. In contrast, incubation of LR11-transfected THP-1 cells with neutralizing anti-CD9 monoclonal antibodies increased the amount of sLR11 released from the cells. Likewise, the PMA-stimulated release of sLR11 increased in THP-1 cells transfected with CD9-targeted shRNAs, which was negated by treatment with the metalloproteinase inhibitor GM6001. These results suggest that the tetraspanin CD9 modulates the ADAM17-mediated shedding of LR11 in various leukemia cell lines and that the association between LR11 and CD9 on the cell surface has an important role in the ADAM17-mediated shedding mechanism.

Expression and Clinicopathological Significance of CD9 in Gastrointestinal Stromal Tumor

This study investigated the expression and clinicopathological significance of CD9 in gastrointestinal stromal tumor (GIST). Immunohistochemistry staining for CD9 was performed on tumor tissues from 74 GIST patients. The correlation with clinicopathological features, risk classification and prognosis was analyzed. CD9-positive staining comprised 59.5% (44/74) of the GIST patients. The CD9-positive expression rate of the sample was significantly associated with diameter (P = 0.028), mitotic counts (P = 0.035), risk classification (P = 0.018) and three-year recurrence-free survival (RFS) (P < 0.001). Cox proportional hazards regression (HR = 0.352; P = 0.015) showed that CD9 is an independent factor for post-operative RFS. The subgroup analysis showed that CD9 expression in gastric stromal tumor (GST) is significantly associated with diameter (P = 0.031), risk classification (P = 0.023) and three-year RFS (P = 0.001). The Cox proportional hazards regression (HR = 0.104; P = 0.006) also showed that CD9 is an independent factor for RFS of GST. However, CD9 expression does not have a statistically significant correlation with clinicopathological features, risk classification, and prognosis in non-GST. In conclusion, CD9 expression in GIST appears to be associated with the recurrence and/or metastasis of GIST patients, especially in GST, which may indicate the important role of CD9 in the malignant biological behavior and prognosis of GST.

Immunophenotyping of leukemic stem cells and chromosome karyotype characteristics in Uyghur leukemia pediatric patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the immunophenotype and chromosome karyotype characteristics of leukemic stem cells (LSC) in Uyghur leukemia pediatric patients.</p><p><b>METHODS</b>The morphological features of LSC in culture in vitro was observed by flow cytometry. The immunophenotype was assessed by detective flow cytometry. The chromosome karyotype was analyzed by R-banding technique.</p><p><b>RESULTS</b>The LSC showed suspended floating colonies growing in the culture medium, and grew well and proliferated constantly in culture over 8 months. Among the 13 children with AML, there were 10 CD34(+)CD38(-)CD123(+) and CD33(+) cases, 10 CD44(+) cases, 10 CD96(+) cases, and 5 CD90(+) cases. Among the 13 children with B-ALL, there were 6 CD34(+)CD20(-)CD19(+) cases, 7 CD9(+) cases, and 5 CD123(+) cases. Among the 9 children with acute T lymphoblastic leukemia (T-ALL), there were 5 CD34(+)CD7(-) and CD90(+) cases, and 4 CD123(+) cases. Among the 13 cases of AML, 5 cases showed chromosome translocation t(15;17), one case chromosome translocation t(8;21), and 7 cases showed no chromosome karyotype abnormality. Among the 22 ALL cases, there were chromosome translocation t(12;21) in 1 case, t(9;22) in 3 case, hyperdiploid in 2 cases, and 16 cases without karyotype abnormalities. Twenty-nine children received induction remission therapy. Among them, 12 died, including 9 CD96(-)positive cases and 3 CD96(-)negative cases, with a statistically significant difference (P < 0.05).</p><p><b>CONCLUSIONS</b>The LSC of Uyghur leukemia pediatric patients in Xinjiang express CD9 and CD19 in ALL, and express CD123 and CD90 simultaneously in ALL and AML. The expression of CD96 is one of factors of poor prognosis.</p>

Clinical significance of SKP2 and MRP-1/CD9 expression in glottic carcinoma and adjacent tissues / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the expression of SKP2 and MRP-1/CD9 protein in glottic cancer and adjacent tissues, and to analyze its significance for a safe surgical margin.@*METHOD@#Thirty-eight cases of glottic squamous cell carcinoma were studied for its cancer tissue, tissue 2 mm, 5 mm, and 10 mm away from cancer, and 10 cases of vocal cord polyp were served as control. SKP2 and MRP-1/CD9 protein were examined by immunohistochemical method.@*RESULT@#The positive expression of SKP2 proteins decreased in sequence of polyp mucosa, those adjacent to carcinoma (10 mm, 5 mm, 2 mm ) and cancer tissue, and there was significant difference between them (P < 0.05); On the contrary, the positive expression of the MRP-1/CD9 proteins increased in sequence of polypous mucosa, those adjacent to carcinoma (10 mm, 5 mm, 2 mm) and cancer tissue,and there was significant difference between them (P < 0.05).@*CONCLUSION@#SKP2 and MRP-1/CD may act as the reference index for judging the biological specialty of LSCC. It is appropriate to regard 5 mm or above 5 mm away from tumors as a safe margin for surgical treatment of glottic carcinoma.

Expression of neutral endopeptidase and motility-related protein-1 in cutaneous malignant melanoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of neutral endopeptidase (CD10) and motility-related protein-1 (CD9) in malignant melanoma and their clinical significance.</p><p><b>METHODS</b>Immunohistochemical study for CD10 and CD9 using Streptavidin-biotin complex technique was carried out in 48 cases of primary cutaneous malignant melanoma (CMM), 23 cases of metastatic melanoma and 23 cases of benign nevus.</p><p><b>RESULTS</b>The positivity rate of CD10 was highest in metastatic melanoma and lowest in benign nevus (P < 0.01). In contrast, the positivity rate of CD9 in metastatic melanoma was lower than that in CMM (P < 0.05). The expression of CD9 was inversely correlated with that of CD10 in malignant melanoma (CMM: r = -0.40, P = 0.005; metastatic MM: r = -0.44, P = 0.034). The expression of CD10 and CD9 in CMM also correlated with tumor histology, Clark's level of invasion and presence of nodal metastasis. A similar relationship was also observed for CD10 and CD9 expression in stromal fibroblasts of CMM (r = -0.43, P = 0.007).</p><p><b>CONCLUSIONS</b>CD10 and CD9 expression correlates with the invasiveness and metastatic potential of malignant melanoma; both factors may demonstrate a counteracting effect. These two markers have potential implications in prognostic assessment of CMM. Stromal fibroblasts may also play an important role in the progression of CMM.</p>

Expression and gene mutation of cluster of differentiation 9 in lung cancer cells induced by mineral powder in Gejiu / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the expression and gene mutation of cluster of differentiation 9 (CD9) in the pathway of the mineral powder induced malignant transformation in immortalized human bronchial epithelial cells (BEAS-2B) in Gejiu.</p><p><b>METHODS</b>BEAS-2B cells served as the control group and its malignant transformation cells induced by mineral powder in Gejiu were considered as experiment group. The expression of CD9 protein in 20 bottles of BEAS-2B cells and 20 bottles of malignant transformation cells was evaluated by immunocytochemistry. The mRNA expression of CD9 in 10 bottles of BEAS-2B cells and 10 bottles of malignant transformation cells was examined by reverse transcriptase polymerase chain reaction (RT-PCR). Gene mutation was detected in the products of RT-PCR by DNA sequencing.</p><p><b>RESULTS</b>There was significant difference between the expression of CD9 protein in BEAS-2B cells (100%, 20/20) and that in its malignant transformation cells (35%, 7/20 P < 0.01). The expression of CD9 mRNA in BEAS-2B cells 0.91 +/- 0.09 was significantly higher than that in its malignant transformation cells (0.34 +/- 0.14) (P < 0.01). Two point mutation of CD9 gene was detected in the malignant transformation cells of BEAS-2B by DNA sequencing. The change of G-->T in the base of 231 led to the change of Gln-->His in the amino acids of 40. The change of T-->A in the base of 119 led to the change of Val-->Asp in the amino acids of 3.</p><p><b>CONCLUSION</b>The absence or down-regulation of CD9 expression and point mutation in the malignant transformation cells of BEAS-2B may play a considerable role in the pathway of the malignant transformation in the BEAS-2B cells induced by mineral powder in Gejiu.</p>

Splenic lymphangioma: clinicopathologic and immunohistochemical study of 18 cases and review of literature / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and differential diagnosis of splenic lymphangioma.</p><p><b>METHODS</b>Eighteen cases of splenic lymphangioma were retrieved from the pathology archives during the period between January 1990 to December 2005. The clinicopathologic features were analyzed. Immunohistochemical study was performed on the paraffin sections of 16 cases.</p><p><b>RESULTS</b>The age of the patients ranged from 9 to 72 years (median = 40 years). Thirteen patients were males and 5 were females. Clinically, the tumor could be asymptomatic or present with abdominal symptoms and hypersplenism. Follow-up information was available in 13 patients (72.2%) and the duration varied from 5 months to 15 years. All 13 patients had an uneventful clinical course, with no evidence of residual disease, local recurrence or metastasis. Gross examination showed splenic enlargement. The tumor appeared as cystic (8/18), solid (5/18) or honeycomb mass (5/18), either solitary (5/18) or multifocal (13/18). Histologically, splenic lymphangioma could be subclassified as cavernous (9/18), cystic (5/18) or mixed (4/18). Immunohistochemical study showed that the positivity rates for CD9 and D2-40 were 100% and 43.8% respectively.</p><p><b>CONCLUSIONS</b>Splenic lymphangioma is a rarely encountered entity that can be misdiagnosed as a splenic hemangioma. A definite diagnosis depends on pathologic examination.</p>

Identification of Gene Expression Signatures in Korean Acute Leukemia Patients

BACKGROUND: In acute leukemia patients, several successful methods of expression profiling have been used for various purposes, i.e., to identify new disease class, to select a therapeutic target, or to predict chemo-sensitivity and clinical outcome. In the present study, we tested the peripheral blood of 47 acute leukemia patients in an attempt to identify differentially expressed genes in AML and ALL using a Korean-made 10K oligo-nucleotide microarray. METHODS: Total RNA was prepared from peripheral blood and amplified for microarray experimentation. SAM (significant analysis of microarray) and PAM (prediction analysis of microarray) were used to select significant genes. The selected genes were tested for in a test group, independently of the training group. RESULTS: We identified 345 differentially expressed genes that differentiated AML and ALL patients (FWER < 0.05). Genes were selected using the training group (n=35) and tested for in the test group (n=12). Both training group and test group discriminated AML and ALL patients accurately. Genes that showed relatively high expression in AML patients were deoxynucleotidyl transferase, pre-B lymphocyte gene 3, B-cell linker, CD9 antigen, lymphoid enhancer-binding factor 1, CD79B antigen, and early B-cell factor. Genes highly expressed in ALL patients were annexin A 1, amyloid beta (A4) precursor protein, amyloid beta (A4) precursor-like protein 2, cathepsin C, lysozyme (renal amyloidosis), myeloperoxidase, and hematopoietic prostaglandin D2 synthase. CONCLUSION: This study provided genome wide molecular signatures of Korean acute leukemia patients, which clearly identify AML and ALL. Given with other reported signatures, these molecular signatures provide a means of achieving a molecular diagnosis in Korean acute leukemia patents.

Differential expression of motility-related protein-1/CD9 gene in gastric cancers and premalignant lesions / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To clone and identify gastric cancer-related genes and explore the possible pathogenic mechanism of gastric cancer.</p><p><b>METHODS</b>The differentially expressed cDNA bands were isolated by fluorescent mRNA differential display in gastric cancer specimens, matched normal gastric mucosa and premalignant lesions. The motility-related protein-1 (MRP-1/CD9) gene was one of the down-regulated genes. MRP-1/CD9 gene expression in different kinds of gastric tissue was analyzed by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>MRP-1/CD9 expression was down-regulated in all gastric cancer tissues. Northern blot analysis confirmed this differential expression. RT-PCR analysis showed that the MRP-1/CD9 gene expression was much lower in gastric cancers(0.31+/-0.18) than in the matched normal gastric tissue (0.49+/-0.24) and in the premalignant lesions (0.47+/-0.18) (P<0.05), and its expression in intestinal type gastric cancer (0.38+/-0.16) was higher than that in diffuse type gastric cancer (0.22+/-0.17) (P<0.05).</p><p><b>CONCLUSION</b>The MRP-1/CD9 gene expression was down-regulated in gastric cancer, its expression was probably related to the carcinogenesis and histology types of gastric cancer.</p>