Serum CD44 Levels Research Articles

Serum CD44 levels in early pregnancy and its genetic variants for increased risk of gestational diabetes mellitus in Chinese pregnant women

This study aimed to explore associations of serum cluster of differentiation 44 (CD44) levels and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational week). Binary conditional logistic regressions were performed to examine associations of serum CD44 levels and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 levels in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 levels and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12–3.40 & 1.95, 1.05–3.61). Furthermore, after adjustment for serum CD44 levels, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98–3.48). In conclusion, serum CD44 levels and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. SignificanceRecent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 plays a causal role in occurrence of GDM. Specifically, it remains unknown whether serum CD44 levels in early pregnancy and its genetic variants can predict the later occurrence of GDM. In this study, we found that high serum CD44 levels in early pregnancy and its genetic variants were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 levels and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms.

CD44 expression in renal tubular epithelial cells in the kidneys of rats with cyclosporine-induced chronic kidney disease.

Renal tubular epithelial cell (TEC) injury is the most common cause of drug-induced kidney injury (DIKI). Although TEC regeneration facilitates renal function and structural recovery following DIKI, maladaptive repair of TECs leads to irreversible fibrosis, resulting in chronic kidney disease (CKD). CD44 is specifically expressed in TECs during maladaptive repair in several types of rat CKD models. In this study, we investigated CD44 expression and its role in renal fibrogenesis in a cyclosporine (CyA) rat model of CKD. Seven-week-old male Sprague-Dawley rats fed a low-salt diet were subcutaneously administered CyA (0, 15, or 30 mg/kg) for 28 days. CD44 was expressed in atrophic, dilated, and hypertrophic TECs in the fibrotic lesions of the CyA groups. These TECs were collected by laser microdissection and evaluated by microarray analysis. Gene ontology analysis suggested that these TECs have a mesenchymal phenotype, and pathway analysis identified CD44 as an upstream regulator of fibrosis-related genes, including fibronectin 1 (Fn1). Immunohistochemistry revealed that epithelial and mesenchymal markers of TECs of fibrotic lesions were downregulated and upregulated, respectively, and that these TECs were surrounded by a thickened basement membrane. In situ hybridization revealed an increase in Fn1 mRNA in the cytoplasm of TECs of fibrotic lesions, whereas fibronectin protein was localized in the stroma surrounding these tubules. Enzyme-linked immunosorbent assay revealed increased serum CD44 levels in CyA-treated rats. Collectively, these findings suggest that CD44 contributes to renal fibrosis by inducing fibronectin secretion in TECs exhibiting partial epithelial-mesenchymal transition and highlight the potential of CD44 as a biomarker of renal fibrosis.

Comparative proteome analysis identified CD44 as a possible serum marker for docetaxel resistance in castration-resistant prostate cancer.

Baseline or acquired resistance to docetaxel (DOC) represents a significant risk for patients with metastatic prostate cancer (PC). In the last years, novel therapy regimens have been approved providing reasonable alternatives for DOC‐resistant patients making prediction of DOC resistance of great clinical importance. We aimed to identify serum biomarkers, which are able to select patients who will not benefit from DOC treatment. DOC‐resistant PC3‐DR and DU145‐DR sublines and their sensitive parental cell lines (DU145, PC3) were comparatively analyzed using liquid chromatography‐coupled tandem mass spectrometry (LC‐MS/MS). Results were filtered using bioinformatics approaches to identify promising serum biomarkers. Serum levels of five proteins were determined in serum samples of 66 DOC‐treated metastatic castration‐resistant PC patients (mCRPC) using ELISA. Results were correlated with clinicopathological and survival data. CD44 was subjected to further functional cell culture analyses. We found at least 177 two‐fold significantly overexpressed proteins in DOC‐resistant cell lines. Our bioinformatics method suggested 11/177 proteins to be secreted into the serum. We determined serum levels of five (CD44, MET, GSN, IL13RA2 and LNPEP) proteins in serum samples of DOC‐treated patients and found high CD44 serum levels to be independently associated with poor overall survival (p = 0.001). In accordance, silencing of CD44 in DU145‐DR cells resulted in re‐sensitization to DOC. In conclusion, high serum CD44 levels may help identify DOC‐resistant patients and may thereby help optimize clinical decision‐making regarding type and timing of therapy for mCRPC patients. In addition, our in vitro results imply the possible functional involvement of CD44 in DOC resistance.

Investigation of osteopontin and CD44 levels in patients with temporomandibular joint disorders

BackgroundThe information about the cellular and molecular mechanisms underlying the formation and progression of temporomandibular joint disorders (TMDs) is limited and the etiology of these disorders is still controversial. Biochemical analyzes are an important tool in understanding the pathogenesis of these diseases. ObjectiveThe main aim of the present study was to investigate the role of serum osteopontin (OPN) and CD44 levels in the etiopathology and to determine whether they could be used as biochemical markers in the diagnosis of TMDs. MethodsTotal number of 54 patients who diagnosed with TMD and total of 34 healthy controls with no joint problems were included in this study. Blood samples were obtained from all patients and then serum samples were analyzed by OPN and CD44 enzyme-linked immunosorbent assay (ELISA). ResultsAccording to the control group, there was a significant decrease in OPN levels in patients with TMDs. However, no statistically significant difference was found in CD44 levels among the groups. ConclusionsFindings obtained in the present study suggest that OPN may play a key role in the pathogenesis of TMDs as a novel biomarker in the diagnosis of these diseases.

Abnormal CD44 activation of hepatocytes with nonalcoholic fatty accumulation in rat hepatocarcinogenesis.

BACKGROUNDPrevalence of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing, and NAFLD has become one of the most common chronic liver diseases worldwide. With abnormal CD44 activation, the severe form of NAFLD can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Thus, the molecular mechanism of CD44 in NAFLD needs to be identified.AIMTo investigate the relationship between CD44 activation and malignant transformation of rat hepatocytes under nonalcoholic lipid accumulation.METHODSSprague-Dawley rats were fed a high-fat (HF) for 12 wk to entice NAFLD and then with HF plus 2-fluorenylacetamide (0.05%) to induce HCC. Rats were sacrificed every 2 wk, and subsequently divided into the groups based on liver pathological examination (hematoxylin and eosin staining): NAFLD, denaturation, precancerosis, HCC, and control. Liver CD44 mRNA was detected by OneArray. Liver fat as assessed by Oil red O staining or CD44 by immunohistochemical assay was compared with their integral optic density. Serum CD44, alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol, and AFP levels were quantitatively tested.RESULTSElevated CD44 was first reported in hepatocarcinogenesis, with increasing expression from NAFLD to HCC at the protein or mRNA level. The CD44 integral optic density values were significantly different between the control group and the NAFLD (t = 25.433, P < 0.001), denaturation (t = 48.822, P < 0.001), precancerosis (t = 27.751, P < 0.001), and HCC (t = 16.239, P < 0.001) groups, respectively. Hepatic CD44 can be secreted into the blood, and serum CD44 levels in HCC or precancerous rats were significantly higher (P < 0.001) than those in any of the other rats. Positive correlations were found between liver CD44 and CD44 mRNA (rs = 0.373, P = 0.043) and serum CD44 (rs = 0.541, P = 0.002) and between liver CD44 mRNA and serum CD44 (rs = 0.507, P = 0.004). Moreover, significant correlations were found between liver CD44 and liver AFP (rs = 0.572, P = 0.001), between serum CD44 and serum AFP (rs = 0.608, P < 0.001), and between CD44 mRNA and AFP mRNA (rs = 0.370, P = 0.044).CONCLUSIONThe data suggested that increasing CD44 expression is associated with the malignant transformation of hepatocytes in NAFLD.

Quantitative detection and clinical value of CD44 in patients with nonalcoholic fatty liver disease

Objective: To quantitatively detect CD44 expression in patients with nonalcoholic fatty liver disease (NAFLD) for comparative analysis. Methods: Patients with chronic liver diseases accompanied with or without NAFLD, including chronic hepatitis B, cirrhosis and hepatocellular carcinoma after chronic hepatitis B, and healthy blood donors as normal controls who admitted to the Affiliated Hospital of Nantong University from May to October 2018 were selected. The proportion of CD44 positive cells was analyzed by flow cytometry. CD44 level was quantified by an enzyme-linked immunosorbent assay, and the biochemical indicators such as serum aspartate aminotransferase, alanine aminotransferase activity, total cholesterol and triglyceride were routinely analyzed. The cancerous and adjacent cancerous tissues of patients accompanied with or without NAFLD were collected by self-matching method and analyzed by immunoblotting and histochemistry and compared by CD44 integrated optical density. Image-Pro Plus version 6.0, Image J, GraphPad Prism 5.0, Photoshop, Microsoft Excel and IBM SPSS statistics 23 were used to analyze and draw pictures. An independent sample t-test was used to compare the differences between groups. Results: Patients accompanied with NAFLD had hepatocyte injury and dyslipidemia. NAFLD and chronic liver disease patients had significantly elevated serum CD44 levels than normal control group (P < 0.01). CD44 positive lymphocyte ratio was 78.19 % ± 16.33 % in NAFLD patients and 68.47% ± 20.91% in chronic hepatitis B group, which was higher than the control group (46.51% ± 20.52%). Chronic hepatitis B group with steatosis had significantly higher CD44 concentration (181.42 ± 49.36) ng/ml than chronic hepatitis B group (142.52 ± 53.87) ng/ml and normal control group (99.47 ± 15.23) ng/ml. CD44/GAPDH ratio in the liver cancer group (1.306 ± 0.614) was significantly higher than paracancerous group (0.477 ± 0.291) and the difference between the two groups was statistically significant (t = 3.451, P = 0.004). The integrated optical density of CD44 in the NAFLD-related liver cancer and paracancerous group were 25.721 ± 5.881 and 14.155 ± 4.001 and the difference between the groups was statistically significant (t = 14.544, P < 0.001). The pathological features of high expression of CD44 in patients with hepatocellular carcinoma were significantly correlated with HBV infection, tumor size, single/multi-center, and lymph node metastasis, degree of differentiation, TNM grade, Child-Pugh score, portal vein tumor thrombus and extrahepatic metastasis. HCC patients with NAFLD had significantly higher serum CD44 (234.62 ± 69.40) ng/ml than patients without NAFLD (186.49 ± 58.89) ng/ml (t = -3.191, P = 0.002), but there was no statistically significant difference in the clinicopathological characteristics between the high/low CD44 groups of HCC patients with NAFLD. Conclusion: The results suggest that CD44 is abnormally activated and its mechanism may play an important role in the progression of NAFLD.

Prognostic significance of elevated serum CD44 levels in patients with oral squamous cell carcinoma.

Availability of reliable methods distinguishing high-risk recurrent tumours from regressive tumours prior to surgery could help in better management of the disease. This study was aimed to estimate pre-surgical serum CD44 concentration and assess the possibility of using it as a non-invasive prognostic tool in oral cancer. ELISA was performed on pre-surgical serum samples from 64 primary oral cancer patients and 16 healthy individuals to estimate soluble CD44 levels. Immunohistochemistry was performed on parallel 64 solid tumours and 10 recurrent tumours. All patients clinically followed up for median period of 19.2 months and obtained prognostic information correlated with CD44 concentration in serum as well as in tumours. Serum CD44 concentration was found significantly high in patients as compared to healthy individuals (P < .001) and also in patients whose disease locally recurred as compared to those did not recur (P = 0026). High serum CD44 concentration inversely affected on patients survival (P = .032). CD44v6 staining intensity was detected significantly high in recurrent tumours as compared to primary tumours (P < .001), and it also correlated with poor survival (P < .001). Furthermore, in combination, patients with increased CD44 concentration in serum and CD44v6 expression in tumours significantly correlated with local recurrence (P < .001) and poor survival (P < .001). Our data suggest that the ELISA-based estimation of pre-surgical serum CD44 concentration could be a non-invasive reliable method distinguishing high-risk recurrent tumours which can further assist in post-surgery treatment planning.

Breast cancer stem cell markers CD44 and ALDH1A1 in serum: distribution and prognostic value in patients with primary breast cancer.

Background: CD44 and ALDH1 have been recognized as the most widely used markers to identify breast cancer stem cells (BCSCs). However, limited to tissue sample and rare population, BCSCs have always been not easily detected. We aimed to measure CD44 and ALDH1A1 (major contributor to ALDH1 activity) levels in serum and explore the prognostic value in primary breast cancer patients.Methods: This study included 140 primary breast cancer patients with stage I-III. Serum samples were collected before surgery and stored at -80 degrees. CD44 and ALDH1A1 were measured by chemiluminescent assay.Results: High serum CD44 levels (≥ 417.4 ng/mL) were correlated with postmenopausal status (P = 0.006), estrogen receptor negativity (P = 0.025), progesterone receptor negativity (P = 0.002) and adjuvant chemotherapy (P = 0.003). The mean serum CD44 levels of luminal group (406.4 ± 68.3 ng/mL) were significantly lower than triple negative group (506.8 ± 175.5 ng/mL) (P < 0.001). There was no correlation between serum ALDH1A1 levels and molecular subtypes. Multivariate analysis revealed that high serum CD44 level (≥ 417.4 ng/mL), was an independent factor for PFS (P = 0.019) and OS (P = 0.008). However, serum ALDH1A1 has no impact on either PFS (P = 0.613) or OS (P = 0.441).Conclusion: Serum CD44 was an independent prognostic indicator in primary breast cancer. However, serum ALDH1A1 has no impact on survivals and might not be an appropriate candidate to predict prognosis for breast cancer.

Immunohistochemical Expression and Serum Levels of CD44 as Prognostic Indicators in Patients with Non-Small Cell Lung Cancer

Background/Objectives: CD44 is often expressed in various types of tumor cells and involved in a number of biological behaviors of malignancy. The present study focused on the clinical significance of the expression of CD44st and CD44v6 in non-small cell lung cancer (NSCLC). Methods: The cohort consisted of 261 consecutive patients who had undergone complete resection of NSCLC. CD44 expression was evaluated in surgical specimens by immunohistochemical staining. Serum CD44 levels were determined using a sandwich ELISA (enzyme-linked immunosorbent assay). Results: In the immunohistochemical analysis, significant correlations were observed between CD44 expression and clinicopathological factors such as the T factor, N factor, pathological stage, and histological type. The 5-year survival rates according to CD44v6 expression were 65.8 and 80.6% in the higher and lower expression groups, respectively (p = 0.0053). According to ELISA, the group with higher expression of serum CD44v6 also showed a significantly more unfavorable prognosis than the lower expression group (p = 0.014). According to multivariate analysis using these significant variables, serum CD44v6 level was found to be an independent prognostic factor (p = 0.048). Conclusions: CD44v6 overexpression and higher serum CD44v6 levels were found to be significantly unfavorable prognostic factors.

CD44 immune receptor linked to diabetes

Genome-wide association studies (GWAS) have identified numerous genes associated with type 2 diabetes, but selecting candidate genes for further verification can be problematic. This study used an expression-based GWAS in which data from 130 publicly available independent microarray experiments were collated to identify genes involved in the pathogenesis of type 2 diabetes. The gene encoding the immune cell receptor CD44 was the top-ranked gene. Follow-up studies showed that treatment of a mouse model with a CD44-targeted antibody decreased blood glucose levels, and that serum CD44 levels correlated with insulin resistance and glycaemic control in humans.

Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes

Type 2 diabetes (T2D) is a complex, polygenic disease affecting nearly 300 million people worldwide. T2D is primarily characterized by insulin resistance, and growing evidence has indicated the causative link between adipose tissue inflammation and the development of insulin resistance. Genetic association studies have successfully revealed a number of important genes consistently associated with T2D to date. However, these robust T2D-associated genes do not fully elucidate the mechanisms underlying the development and progression of the disease. Here, we report an alternative approach, gene expression-based genome-wide association study (eGWAS): searching for genes repeatedly implicated in functional microarray experiments (often publicly available). We performed an eGWAS across 130 independent experiments (totally 1,175 T2D case-control microarrays) to find additional genes implicated in the molecular pathogenesis of T2D and identified the immune-cell receptor CD44 as our top candidate (P = 8.5 × 10(-20)). We found CD44 deficiency in a diabetic mouse model ameliorates insulin resistance and adipose tissue inflammation and also found that anti-CD44 antibody treatment decreases blood glucose levels and adipose tissue macrophage accumulation in a high-fat, diet-fed mouse model. Further, in humans, we observed CD44 is expressed in inflammatory cells in obese adipose tissue and discovered serum CD44 levels were positively correlated with insulin resistance and glycemic control. CD44 likely plays a causative role in the development of adipose tissue inflammation and insulin resistance in rodents and humans. Genes repeatedly implicated in publicly available experimental data may have unique functionally important roles in T2D and other complex diseases.

Serum osteopontin and CD44 levels in lymphoreticular malignancies in children

Osteopontin (OPN) is an adhesive glycoprotein that interacts with a variety of cell surface receptors, including several integrins and CD44. OPN is expressed and secreted by numerous human malignancies. CD44 play an important role in tumor growth and metastasis. We aimed to evaluate serum levels of osteopontin and CD44 in patients with lymphorethicular malignancies in childhood. We studied serum levels of CD44 and OPN levels of 54 patients (26, 18 and 10 patients with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and acute lymphoblastic leukemia (ALL), respectively) at the diagnosis. The mean levels of OPN were significantly higher in patients (5.42±8.24 ng/ml) than in controls (3.89 ±1.96 ng/ml). The mean levels of CD44 levels were also significantly higher in patients (3.82±2.31 ng/ml) than in controls (1.96±0.62 ng/ml), and significantly higher in the advanced stages than in early stages. The mean levels of the CD44 in NHL, HL and ALL were 3.49±2.00, 3.56±1.74, and 5.15±3.50 respectively. OPN and CD44 levels were found to be increased in parallel (p=0.003). A more advanced disease and/or poor prognostic factors were seen in 9 patients who had both serum CD44 and OPN levels higher than 2SD of the control. Elevated levels of both CD44 and OPN at the diagnosis may predict an unfavorable outcome in childhood leukemias and lymphomas (Tab. 2, Fig. 3, Ref. 44).

P2-01-14: High Level of CD44 Expression and Soluble CD44 Secretion Mediate Trastuzumab Resistance in HER2 Positive Breast Cancer.

Abstract Background: Overexpression of HER2 occurs in 15–25% of invasive breast cancer. Trastuzumab, a humanized monoclonal antibody targeting the extracellular domain of HER2, markedly improves disease-free and overall survival in patients with HER2−positive breast cancer. However, resistance to trastuzumab develops in most patients with HER2−overexpressing metastatic breast cancer. Breast cancer stem cells have been shown to express HER2, although its role in the development or maintenance of stem cells is not well characterized. CD44 is one of the proposed markers for breast cancer stem cells. We investigated the role of CD44 in acquired trastuzumab resistance in HER2 positive breast cancer. Methods: CD44 mRNA expression was measured by quantitative real-time PCR. The proportion of CD44 positive cells was measured by fluorescence-activated cell sorting (FACS). Soluble CD44 level was detected by enzyme-linked immunosorbent assay (ELISA). In vitro tumorigenicity was evaluated by soft agar colony formation assay. Cell invasion was tested by using a matrigel invasion assay. In vivo tumor growth was evaluated using a mammary fat pad xenograft mouse model. Results: CD44 mRNA expression, CD44 positive cell population by FACS, and CD44 secretion were significantly increased in both SKBR3 derived trastuzumab resistant SKBR3 clone 3 and BT474 derived trastuzumab resistant HR20 cells compared to parental, trastuzumab sensitive cells. Consistent with the increase in CD44, trastuzumab resistant cells showed an increase in soft agar colony formation and cell invasion, which were blocked by siRNA-induced downregulation of CD44 expression. Tumor growth and incidence were enhanced in mice injected with trastuzumab resistant HR20 cells compared to the mice injected with trastuzumab sensitive parental BT474 cells. Knock-down of CD44 expression by the transfection with CD44-specific siRNA suppressed in vivo tumor growth in the mice injected with trastuzumab resistant HR20 cells. Finally, we found high serum CD44 levels correlated with advanced tumor progression in HER2 positive breast cancer. Conclusion: Our findings indicate that high levels of CD44 mediate trastuzumab resistance in HER2 positive breast cancer cells as well as tumor progression in mice. Circulating CD44 is prognostic in patients with HER2 positive breast cancer. CD44 may be a therapeutic target for HER2 positive breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-14.

Prognostic value of serum CD44, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels in patients with indolent non-Hodgkin lymphomas

Elevated serum CD44, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been linked to poor prognosis in aggressive lymphomas, but their utility in low grade lymphomas remains undefined. We evaluated serum CD44, VCAM-1 and ICAM-1 levels in 100 patients with newly diagnosed indolent NHL. The median pre-treatment values of the markers were as follows: CD44 540 ng/mL (range 156–1201), ICAM-1 311 ng/mL (range 102–1222) and VCAM-1 1165 ng/mL (range 248–4779). On univariate analysis, elevated sCD44, sICAM-1 and sVCAM-1 were significantly associated with worse overall (OS) and progression-free survival (PFS). In a subset analysis of patients with stage IV disease, the effects of sCD44 and sICAM-1 on OS persisted (p<0.05), as did the effect of sCD44 on PFS (p<0.01). In a multivariate analysis that included conventional prognostic factors and the Follicular Lymphoma International Prognostic Index (FLIPI) model, sICAM-1 demonstrated prognostic value for OS and PFS. We conclude that serum CD44, ICAM-1 and VCAM-1 can potentially be prognostic in patients with indolent NHL. Though the FLIPI model remains the gold standard for prognosis, these quantitative serologic markers may be useful as adjunct tools in assessing disease risk.

Serum CD44 levels and overall survival in patients with HER2-positive breast cancer

CD44 is an adhesion molecule involved in tumor cell invasion and metastasis. The function of CD44 in breast cancer is not understood completely, or is its role as a predictive or prognostic factor. In this study, we tested for the hypothesis that the concentration of soluble CD44 (sCD44) in serum is correlated with clinicopathological factors, especially HER2, and survival in patients with breast cancer. We retrospectively identified 110 patients with breast cancer who had been treated at The University of Texas MD Anderson Cancer Center (MDACC) from September 2001 to May 2004. Sera were collected before definitive surgery in patients with stage I or II breast cancer, before initiation of neoadjuvant chemotherapy (if indicated) for patients with stage I-III breast cancer, and before initiation of systemic therapy in patients with stage IV breast cancer. sCD44 levels were determined using an enzyme-linked immunosorbent assay. The median age at diagnosis was 51 years (range, 28.6-87.1 years). sCD44 concentration was correlated with tumor stage (P = 0.0308). sCD44 serum concentration did not predict pathological response in patients treated with neoadjuvant chemotherapy. Among patients with distant metastases, sCD44 levels were significantly higher in patients with liver involvement than in patients with metastases at other sites. The overall survival rate did not differ between patients with high sCD44 concentration and patients with low sCD44 concentration. However, sCD44 concentration was a significant predictor of overall survival for patients with HER2-positive breast cancer, while no difference in overall survival rates was observed in patients with HER2-negative breast cancer. To the best of our knowledge, this is the first study to show an association between circulating sCD44 levels and survival in HER2-positive breast cancer patients. Our results suggest a role for sCD44 as a prognostic marker. Furthermore, sCD44 level may offer a new clinical therapeutic target in HER2-positive breast cancer.

Soluble CD44 in patients with aggressive non-Hodgkin's lymphoma: Prognostic and clinical value

e19539 Background: CD44 is a cell surface glycoprotein expressed by a large variety of tissues. In addition to their expression on the cell membrane, CD44 proteins are also released from cells, and soluble CD44 proteins are detectable in the normal human circulation. The observation that several human tumors show an overexpression of CD44 and the presence of soluble CD44 in the circulation makes CD44 a potential serum marker for tumor detection. In this prospective study, we investigated the prognostic and clinical value of s-CD44 in patients with aggressive non-Hodgkin's lymphomas. Methods: s-CD44 concentration was measured in the sera of 64 patients with aggressive non-Hodgkin's lymphomas treated with standard CHOP by using chemiluminescence-enzyme immunoassay (EIA). Results: Circulating serum CD44 (s-CD44) levels have been found to change in parallel with response to therapy, but little is known about the predictive or prognostic significance of s-CD44. The median pretreatment s-CD44 level was 510 ng/mL(range, 90 to 2,120 ng/mL). Only 10 (31%) of the 32 patients with an International Prognostic Index (IPI) score 0 or 1 had s-CD44 concentration higher than the median level, whereas 11 (52%) of 21 patients with an IPI score ≥2 had a concentration higher than the median before initiation of treatment (P &lt; .0001). Patients with lower than the median s-CD44 achieved more often a complete response to therapy (P = .0002) and had better survival (P = .007) than those with higher s-CD44 levels. However, in a multivariate analysis, only the IPI score had independent prognostic value (P &lt; .001). Conclusions: Our results showed that a high s-CD44 level before treatment is associated with a high IPI score, poor response to treatment, and unfavorable prognosis in aggressive non-Hodgkin's lymphoma. No significant financial relationships to disclose.

P022 Serum CD44 levels predict survival in patients with low-risk myelodysplastic syndromes

P022 Serum CD44 levels predict survival in patients with low-risk myelodysplastic syndromes

Serum CD44 levels and response to selenium-based therapy in patients with gynecologic cancers

2544 Background: Selenium inhibits the development of carboplatin drug resistance in a mouse ovarian cancer xenograft model and in tissue culture. Selenium inhibits the binding of ovarian cancer cells to hyaluronic acid (HA). HA is the main ligand of the CD44 receptor that is a transmembrane protein implicated in metastases and drug resistance. Based on this data we designed a phase I trial to determine MTD/DLT and any effects of selenium in carboplatin pharmacokinetics (PK) using the combination of selenious acid (Se), carboplatin (C) and paclitaxel (P) in the treatment of chemo-naive women with gynecologic malignancies. A secondary end-point was to test serum CD44 as a surrogate marker of Se effect on in vivo drug resistance. Methods: Based on the doses given on the mouse model, we administered Se intravenously (IV) on day 1, over 5 hours. On day 3, P was given at 175mg/m2 IV over 3 hours, followed by C AUC 5 (Calvert method) for 30 min every 21 days. During the first cycle C was given at an AUC of 5 an...

Are serum levels of CD44 relevant in children with pediatric sarcomas?

Variation in serum levels of CD44, which acts as an adhesion receptor involved in lymphocyte migration and binding, have been reported in some malignancies. The aim of this study is to compare serum levels of CD44 in children with sarcomas with those in healthy children. CD44 levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples taken at diagnosis from 55 children with sarcomas and from 27 healthy children of similar age, sex, and socioeconomic status. There was no statistically significant difference between CD44 serum levels of children with sarcomas and those of healthy children. No significant difference was observed between CD44 serum levels of each patient group and those of control group (P > 0.05). There was no significant difference among CD44 serum levels of patient groups according to stage or outcome. In this study, serum CD44 levels were not found to be of value in the diagnosis or prognosis in children with sarcomas.

Serum levels and differential expression of CD44 in childhood leukemia and malignant lymphoma: correlation with prognostic criteria and survival.

The CD44, a cell surface proteoglycan, participates in a variety of function including tumor dissemination and metastasis. However, there are no available data on the prognostic significance of CD44 expression of tumor tissue correlated with serum sCD44 level in childhood leukemias and lymphomas. Serum levels and leukemic cell tumor tissue expression of CD44 were detected in 54 children with acute leukemia and malignant lymphoma. Serum samples were obtained from all patients before treatment and during remission. Twelve age-matched healthy children were included as a control group. The serum CD44 levels were significantly higher in patients with Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL) and acute lymphoblastic leukemia (ALL) than those in the control group. The median values were 1627.0, 1336.0, 1318.5, 1730.4, 902.7 ng/mL, respectively, and P<0.001, P<0.01, P<0.01, P<0.05 in comparisons, respectively. However, there was no significant difference between acute myeloid leukemia (AML) and the control group (median values: 900.3 and 902.7 ng/mL, respectively, P>0.05). Serum sCD44 levels significantly declined in HD, NHL and ALL patients who were in complete remission (median values: 684.0, 573.8 and 1101.1 ng/mL, respectively, P<0.05 in each comparison). Patients with HD had higher levels of serum sCD44 and correlated well with higher erythrocyte sedimentation rate (ESR), B-symptoms and advanced-stage disease (P<0.05, P<0.05 and P<0.01, respectively). Expression of CD44 was significantly high in patients with HD and NHL who were in advanced stages of disease. High serum CD44 level was also associated with high tumor tissue expression of CD44 in patients with HD and BL. In addition, patients with higher levels of serum sCD44, had a poorer outcome and survival than those with lower sCD44 levels in HD and NHL groups. A high serum sCD44 level and/or tumor tissue expression at diagnosis is associated with poor prognostic criteria and/or unfavorable outcome in childhood leukemias and lymphomas.