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.
Antigens, CD9 ; Colorectal Neoplasms* ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Prognosis

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.
ADAM Proteins/*metabolism ; Antigens, CD9/genetics/*metabolism ; Cell Line, Tumor ; Humans ; LDL-Receptor Related Proteins/genetics/*metabolism ; Leukocytes/*metabolism ; Macrophages/metabolism ; Membrane Transport Proteins/genetics/*metabolism ; Proteolysis

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.
Amyloid ; Antigens, CD79 ; Antigens, CD9 ; B-Lymphocytes ; Cathepsin C ; Diagnosis ; DNA Nucleotidylexotransferase ; Gene Expression* ; Genome ; Humans ; Leukemia* ; Leukemia, Myeloid, Acute ; Lymphoid Enhancer-Binding Factor 1 ; Muramidase ; Peroxidase ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cells, B-Lymphoid ; Prostaglandin D2 ; RNA ; Transcriptome*

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.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD9/*genetics/*metabolism ; Disease-Free Survival ; Female ; Gastrointestinal Neoplasms/metabolism/mortality/*pathology ; Gastrointestinal Stromal Tumors/metabolism/mortality/*pathology ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Risk Factors