Human C-Reactive Protein Binds Activating Fcγ Receptors and Protects Myeloma Tumor Cells from Apoptosis

Yang, Jing; Wezeman, Michele; Zhang, Xiang; Lin, Pei; Wang, Michael; Qian, Jianfei; Wan, Bo; Kwak, Larry W.; Liu, Yu; Yi, Qing

doi:10.1016/j.ccr.2007.08.008

Cited by 110 publications

(88 citation statements)

References 43 publications

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“…35 C-reactive protein (CRP) as well as albumin levels are known to be hallmarks of tumor activity. 36,37 Taking all these facts into consideration, we can anticipate that serum miRNA levels are associated with tumor mass and disease activity. Interestingly, such correlation pattern with biochemical parameters was observed also for MGUS.…”

Section: Discussionmentioning

confidence: 99%

Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nclassification. 22 In this study, a new serum miRNAs expression profile, potent enough to distinguish newly diagnosed MM and MGUS patients from healthy controls, was created based on TaqMan Low Density Arrays (TLDA). This profile was validated by quantitative realtime PCR (qPCR) on a larger cohort of newly diagnosed and relapsed MM as well as MGUS patients. Moreover, miRNAs levels were correlated with clinical, biochemical and cytogenetic characteristics and survival data. Methods Patients and healthy donorsPeripheral blood (PB) serum samples from 103 newly diagnosed MM patients, 18 MM patients in relapse, 57 MGUS and 30 healthy donors (HD) from the Faculty Hospital Brno, Czech Republic, were obtained for this study. PB serum samples were collected as follows: centrifugation 3500 rpm/15 min/20°C. Samples were frozen as 0.5 mL aliquots, stored at -80°C and thawed only once. For 70 MM and 36 MGUS samples, BMPCs were obtained for routine interphase fluorescence in situ hybridization analysis (I-FISH), as described previously. 23 Patients' and donors' characteristics are described in Table 1 and in the Online Supplementary Table S1. For 6 newly diagnosed MM patients, BMPCs and exosomal and non-exosomal fraction from PB serum were collected. All patients signed an informed consent form approved by the hospital ethical committee before enrollment into this study. MiRNA extractionTotal RNA enriched for miRNAs was extracted from all serum samples using miRNeasy Kit (Qiagen) modified for circulating miRNAs according to the manufacturer's instructions. MiRNA/RNA quantity was assessed on a NanoDrop ND-1000 Spectrophotometer (Thermo Scientific) as measurement of each sample 2 times with mean SD=0.292 ng/μL. All samples fit into the Nanodrop ND-1000 validated measuring range. Exosomes precipitationExosomes were collected using ExoQuick Exosome Precipitation Solution (System Biosciences). Serum samples were centrifuged for 3500 rpm/10 min/4°C, 250 μL of serum was combined with 63 μL of ExoQuick, incubated for 30 min/4°C and centrifuged for 2 min/13000 rpm. Exosomal and non-exosomal fraction was used for miRNA/RNA extraction, as described above. TaqMan Low Density ArraysMegaplex profiling using human TaqMan Low Density miRNA Arrays A+B, v3.0 (TLDA) (Life Technologies) was performed to evaluate the expression of 667 miRNA (see Online Supplementary Methods). QPCR was performed on the ABI7900HT system; raw data were analyzed using SDS software v.2.3, RQ Manager v1.2.1 (Life Technologies). Candidate miRNA confirmation by qPCR and quantification of miRNAIndividual TaqMan miRNA assays for 6 miRNA (hsa-miR-222-002276, hsa-miR-744-002324, hsa-miR-130a-000454, hsa-miR34a-000426, hsa-let-7e-002406, hsa-let-7d-002283, Life Technologies) were used for qPCR on a 7500 Real-Time PCR System. QPCR and reverse transcription was performed following the manufacturer´s recommendations (see Online Supplementary Methods). Absolute quantification to determine the copy number of each miRNA per 1...

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Section: Discussionmentioning

confidence: 99%

Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance

et al. 2013

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“…22 A recent study in myeloma demonstrated that CRP directly promoted tumor cell proliferation under stressed conditions and protected myeloma cells from chemotherapy-induced apoptosis. 23 Clearly, further preclinical studies in HCC are needed to elucidate the causal mechanisms of CRP in HCC progression.…”

Section: Discussionmentioning

confidence: 99%

Single determination of C-reactive protein at the time of diagnosis predicts long-term outcome of patients with hepatocellular carcinoma

et al. 2013

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We investigated the prognostic value of C-reactive protein (CRP) in patients with hepatocellular carcinoma (HCC) not amenable to surgery. A total of 615 patients diagnosed with HCC not amenable to surgery between April 1999 and December 2009 at the Department of Gastroenterology of the Medical Universities of Vienna and Innsbruck were included. We assessed the optimal CRP cutoff by regression spline analysis and tested its impact on median overall survival (OS) by the Kaplan-Meier method, univariate analysis (log-rank test), and multivariate analysis (Cox proportional hazard regression model) in a training cohort (n 5 466, Vienna) and an independent validation cohort (n 5 149, Innsbruck). We found a sigmoid-shaped association of CRP and the hazard ratio of death upon regression spline analysis and defined a CRP level <1/1 mg/dL as optimal cutoff for further survival assessments. Elevated CRP (1 mg/dL) at diagnosis was associated with poor OS (CRP-elevated versus CRP-normal; 4 versus 20 months; P < 0.001) and remained a significant negative predictor for OS upon multivariate analysis (hazard ratio, 1.7; P < 0.001), which was independent of age, Child-Pugh class, tumor characteristics, and treatment allocation. Analyses with respect to Barcelona Clinic Liver Cancer (BCLC) stage and Child-Pugh class supported the relevance of CRP (BCLC-stage C and Child-Pugh A: OS for CRP-elevated versus CRP-normal, 6 versus 14; P < 0.001; BCLC-stage C and Child-Pugh B: OS for CRP-elevated versus CRP-normal, 4 versus 15 months; P < 0.001). The prognostic significance of elevated CRP was reproducible at a second CRP determination timepoint and confirmed in the independent validation cohort. Conclusion: Elevated CRP is associated with a dismal prognosis in HCC patients and may become a useful marker for patient selection in HCC management.

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“…A myriad of agents targeting varied facets of the innate immune system, including chemokine, interleukin-6 and tumour necrosis factor antagonists, are already in clinical trial. 7 Furthermore, it is now established that CRP plays a direct role in malignant progression 57 and is itself a valid therapeutic target, 58 with several small molecule inhibitors in development. Future studies must define the interplay between the varied facets of the inflammatory response, including the role of particular leucocyte subtypes and cellular products, to enable the rational design and allocation of anti-inflammatory strategies in this context.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

Neal¹,

Mann²,

Sutton³

et al. 2009

European Journal of Cancer

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Background: There is increasing evidence that the presence of a preoperative systemic inflammatory response (SIR) independently predicts poor long-term outcome in patients with colorectal cancer (CRC).Socioeconomic deprivation was reported to correlate with the presence of the SIR and to itself independently predict poor outcome following primary CRC resection. The aim of this study was to determine the prognostic value of preoperative systemic inflammatory biomarkers and socioeconomic deprivation in patients undergoing resection of colorectal liver metastases (CLM) and to examine correlations between these variables in this context. Results: On multivariable analysis, poor CRS (3-5), high neutrophil count (>6.0 x10 9 /L) and low serum albumin (<40 g/dL) were the only independent predictors of shortened overall survival following metastasectomy, with neutrophil count representing the greatest relative risk of death. These factors were also the only independent predictors of shortened disease-free survival 3 following hepatectomy. Socioeconomic deprivation was associated with neither systemic inflammation nor long-term outcome in this context. Patients and methods: Conclusions:The presence of a preoperative systemic inflammatory response, but not socioeconomic deprivation, independently predicts shortened survival following resection of CLM.4

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Human C-Reactive Protein Binds Activating Fcγ Receptors and Protects Myeloma Tumor Cells from Apoptosis

Cited by 110 publications

References 43 publications

Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance

Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance

Single determination of C-reactive protein at the time of diagnosis predicts long-term outcome of patients with hepatocellular carcinoma

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

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