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 Tumor Cells Is Associated with Poor Prognosis in Patients with Invasive Lobular Carcinoma / 한국유방암학회지

PURPOSE: We investigated the prognostic significance of CD9 expression in tumor cells of patients with invasive lobular carcinoma (ILC). METHODS: CD9 expression was evaluated by immunohistochemistry in 113 ILC tissue samples. Correlation of CD9 expression with the patients' clinicopathological parameters and overall survival was assessed. RESULTS: CD9 expression was detected in 48 (42.5%) ILC patients. However, no significant relation could be determined between CD9 expression and the clinicopathological parameters of the patient including tumor size, lymph node metastasis, lymphovascular invasion, histologic grade, expression of hormone receptors, human epidermal growth factor receptor 2 status, and Ki-67 labeling index. Patients with CD9 expression had worse overall survival (p = 0.051) and disease-free survival (DFS, p = 0.014) compared to patients without CD9 expression. Multivariate analysis revealed that CD9 expression was an independent prognostic factor for DFS (p = 0.049). CONCLUSION: CD9 expression in tumor cells could be a significant prognostic marker in patients with ILC.

Comparison of CD9 & CD146 markers in endometrial stromal cells of fertile & infertile females

Background & objectives: CD9 and CD146 are important adhesion molecules that play a role in the implantation of an embryo. This study was undertaken to correlate the expression of these markers in fertile and infertile women's endometrial stromal cells. Methods: Human endometrial stromal cell culture from endometrial biopsies of fertile (n=50) and infertile females (n=50) was performed and primary cell lines were established. Expression of CD9 and CD146 was studied for all the 100 cell lines with the help of flow cytometry. Gene expression of CD9 and CD146 was performed by real-time polymerase chain reaction. Results: There was a significant difference in endometrial stromal cells of fertile and infertile females. Flow cytometric results revealed significantly lower expression of CD9 (P=0.0126) and CD146 (P=0.0006) in the infertile endometrial stromal cells as compared to fertile endometrial stromal cells. These results were comparable with real-time data. Interpretation & conclusions: This study showed that endometrial stromal cells from infertile females had lower expression of adhesion molecules, CD9 and CD146. Our findings suggest that CD9 and CD146 may have a role in infertility. Infertile female's endometrial stromal cells have decreased expression of CD9 and CD146 which can be the cause of infertility related to implantation failure.

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.

Expression and its clinical significance of CD9 protein in pancreatic cancer / 中华消化杂志

Objective To examine the expression of CD9 protein in pancreatic cancer tissues and adjacent tissues,and to analyze its relation with the progress and prognosis of pancreatic cancer.Methods From September 2005 to December 2009,surgical resected cancer tissues and adjacent tissues of 90 patients with pancreatic cancer and their clinical data were collected.The expression of CD9 protein in pancreatic cancer tissues and adjacent tissues was detected by immunohistochemistry,and its relationship with clinicopathological features was analyzed.Chi-square test was performed for comparison of ratios between groups.Overall survival (OS) analysis of 90 patients after surgery was performed.Results The high expression rate of CD9 protein (64.4％,58/90) in cancer tissue was significantly higher than that in cancer adjacent tissue (45.6％,41/90),the difference has statistically significant (χ2 =6.847,P＜0.05).CD9 protein was highly expressed in most of pancreatic cancer tissue which was well differentiated or without lymph node metastasis (74.6％ (50/67) vs 39.1％ (9/23),χz =9.554,P＜0.01; 50.0％(17/34) vs 73.2％(41/56),χ2 =5.856,P＜0.05 respectively).However,the expression of CD9 was not correlated with gender and age (both P＞0.05).OS and progression-free survival (PFS) of the patients with CD9 highly expressed were significantly longer than those with low expression of CD9 (median OS:33.0 months vs 7.0 months,χ2 =15.400 P＜0.01.Median PFS:30.5 months vs 5.0 months,χ2 =13.750,P＜0.01).Conclusion CD9 protein is a kind of protein related with the invasive ability of pancreatic cancer,which may play a role in progression and metastasis of pancreatic cancer and can help to determine the prognosis to a certain extent.

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.

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 immunoh istochemical 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 polypusmucosa, 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 speciality 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 KAI1/CD82 and MRP-1/CD9 in Transitional Cell Carcinoma of Bladder / 华中科技大学学报（医学）（英德文版）

The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (P＜0.05), but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P＞0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (P＜0.05). Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant (r=0.316, P＜0.05). It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

Expression of MRP1/CD_9 in cervical squamous cell carcinoma tissue and its clinical significance / 肿瘤研究与临床

Objective To investigate the clinical significance in MRP1/CD_9 expression in cervical squamous cancer tissues and normal cervical tissues.Methods The expression of MRP1/CD_9 were assayed by SABC immunohistochemical methods in 53 cases of cervical cancer tissues and 13 cases of normal cervical tissues.Results Positive expression of MRP1/CD_9 was detected in 13 normal cervical tissue.MRP1/D_9 ex- pression is down-regulated in cervical carcinoma(P

Tetraspanin CD9 induces MMP-2 expression by activating p38 MAPK, JNK and c-Jun pathways in human melanoma cells

Expression of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), which correlates with tumor invasion and metastasis, has been known to be regulated by several intracellular signaling pathways. Since the CD9 membrane protein has been implicated in signal transduction and malignant progression of cancer cells, we examined the functional involvement of CD9 in the regulation of MMP-2 and MMP-9 expression by using stable CD9 transfectant clones of MelJuso human melanoma cells. The CD9 cDNA-transfected cells with elevated CD9 expression displayed increased MMP-2 and decreased MMP-9 expression when compared with the mock transfectant cells. Among several signal pathway inhibitors tested, SB203580 and SP600125, which inhibit p38 MAPK and JNK respectively, completely blocked the CD9-stimulated MMP-2 expression. Phosphorylation levels of p38 MAPK and c-Jun in MelJuso cells were also significantly increased by CD9 transfection. In addition, the down-regulation of p38 MAPK and JNK by siRNA transfection resulted in a decrease in MMP-2 expression by MelJuso cells. Promoter analysis and gel shift assay showed that the CD9-induced MMP-2 expression is mediated by a functional AP-1 site through interactions with AP-1 transcription factors including c-Jun. These results suggest that CD9 induces MMP-2 expression by activating c- Jun through p38 MAPK and JNK signaling pathways in human melanoma cells.

Significance of MRP1/CD9 protein expression in human hepatocellular carcinoma / 中国普通外科杂志

Objective To investigate the expression of MRP1/CD9 protein in human hepatocellular carcinoma (HCC),and its relationship to carcinoma invasion and metastasis. Methods The specimens of tissue microarray from 152 primary hepatocellular carcinomas with paracancerous liver tissue, 22 tumor emboli , 4 intrahepatic satellite metastases, 17 extrahepatic metastases ,and 5 normal livers, respectively, were constructed and used for detection of MRP1/CD9 expression by immunohistochemistry. Results Immunohistochemical analysis of tissue microarrays demonstrated MRP1/CD9 protein expression in 27.0%(41/152)of the primary HCCs. The expression of MRP1/CD9 protein was higher in HCCs without cancer thrombi than in those with cancer thrombi (40.48%vs21.82%,P10cm, P20?g/L, P=0.029). Conclusions Loss of MRP1/CD9 protein expression may be associated with invasion and metastases of hepatocellular carcinoma.