CXCR6-CXCL16 Axis Promotes Breast Cancer by Inducing Oncogenic Signaling

Precise mechanisms underlying breast cancer (BrCa) metastasis are undefined, which becomes a challenge for effective treatments. Chemokine signaling instigates the trafficking of cancer cells in addition to leukocytes. This study aimed to ascertain the clinical and biological significance of the CXCR6/CXCL16 signaling axis in the pathobiology of BrCa. Our data show a higher expression of CXCR6 in BrCa cell lines and tissues. Stage-III BrCa tissues express significantly higher CXCR6 compared to stage-II tissues. The ligand, CXCL16, could remain tethered to the cell surface, and, after proteolytic shedding of the ectodomain, the N-terminal fragment is released, converting it to its oncogenic, soluble form. Like CXCR6, N-terminal CXCL16 and ADAM-10 were significantly higher in stage-III than stage-II, but no significant difference was observed in the C-terminal fragment of CXCL16. Further, stimulation of the CXCR6/CXCL16 axis activated Src, FAK, ERK1/2, and PI3K signaling pathways, as per antibody microarray analysis, which also underlie CXCL16-induced F-actin polymerization. The CXCR6/CXCL16 axis induces cytoskeleton rearrangement facilitating migration and invasion and supports BrCa cell survival by activating the PI3K/Akt pathway. This study highlights the significance of the CXCR6/CXCL16 axis and ADAM10 as potential therapeutic targets for advanced-stage BrCa.

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Identification of biomarkers and functional modules from genomic data in stage-wise breast cancer

Current Bioinformatics ◽

10.2174/1574893615999200922123104 ◽

2020 ◽

Vol 15 ◽

Author(s):

Athira K ◽

Vrinda C ◽

Sunil Kumar P V ◽

Gopakumar G

Keyword(s):

Breast Cancer ◽

Expression Patterns ◽

Differential Expression Analysis ◽

Predictive Biomarkers ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Functional Modules ◽

Incidence And Mortality ◽

Multiple Stages

Background: Breast cancer is the most common cancer in women across the world, with high incidence and mortality rates. Being a heterogeneous disease, gene expression profiling based analysis plays a significant role in understanding breast cancer. Since expression patterns of patients belonging to the same stage of breast cancer vary considerably, an integrated stage-wise analysis involving multiple samples is expected to give more comprehensive results and understanding of breast cancer. Objective: The objective of this study is to detect functionally significant modules from gene co-expression network of cancerous tissues and to extract prognostic genes related to multiple stages of breast cancer. Methods: To achieve this, a multiplex framework is modelled to map the multiple stages of breast cancer, which is followed by a modularity optimization method to identify functional modules from it. These functional modules are found to enrich many Gene Ontology terms significantly that are associated with cancer. Result and Discussion: predictive biomarkers are identified based on differential expression analysis of multiple stages of breast cancer. Conclusion: Our analysis identified 13 stage-I specific genes, 12 stage-II specific genes, and 42 stage-III specific genes that are significantly regulated and could be promising targets of breast cancer therapy. That apart, we could identify 29, 18 and 26 lncRNAs specific to stage I, stage II and stage III respectively.

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Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

European Heart Journal ◽

10.1093/ehjci/ehaa946.2144 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P Milani ◽

L Obici ◽

R Mussinelli ◽

M Basset ◽

G Manfrinato ◽

...

Keyword(s):

Natural History ◽

Median Survival ◽

Troponin I ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Wild Type ◽

Staging Systems ◽

Significant Difference ◽

History Of

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P<0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P<0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

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Differing from diseased stage in melanoma, the olfactory receptor gene OR56A4 is expressed

10.31219/osf.io/yz37x ◽

2021 ◽

Author(s):

Bronte Morse ◽

Kobi Decker

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Olfactory Receptor ◽

Receptor Gene ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Olfactory Receptor Gene ◽

Breast Cancer Patients ◽

Receptor Family

We have compared the global profiles of 100 tumors in Stage I, II and III with two independently releasedmicroarray datasets in order to understand their transcriptional behaviors accompanying a progression in breastcancer (1, 2). The olfactive receptor, family 56, subfamily A, member 4 OR56A4, was discovered to have beenone of the genes with the most varied expression when comparing initial tumors in stage I, stage II, and stageIII of breast cancer patients. In the stage III tumors, OR56A4 expression in comparison to the stage I tumorswas lower.

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ATM-Mediated Phosphorylation of Cortactin Involved in Actin Polymerization Promotes Breast Cancer Cells Migration and Invasion

Cellular Physiology and Biochemistry ◽

10.1159/000496048 ◽

2018 ◽

Vol 51 (6) ◽

pp. 2972-2988 ◽

Cited By ~ 5

Author(s):

Lei Lang ◽

Yixuan Hou ◽

Yanlin Chen ◽

Gang Tu ◽

Jing Tao ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Breast Tumor ◽

Breast Cancer Cells ◽

Actin Polymerization ◽

Migration And Invasion ◽

Cancer Cell Migration ◽

Transwell Assay ◽

Atm Kinase ◽

Cell Migration And Invasion

Background/Aims: The ataxia-telangiectasia mutated (ATM) protein kinase is critical for the maintenance of genomic stability and acts as tumor suppressor. Although evidence shows that a DNA damage-independent ATM (oxidized ATM) may be involved in cancer progression, the underlying mechanism is still unclear. Methods: Immunohistochemistry, immunofluorescence and western blotting were applied to detect the levels of oxidized ATM. Transwell assay was used to detect the cell migration and invasion abilities in different treatments. Quantitative phosphoproteome analysis was performed using hypoxic BT549 cells, in the presence or absence of Ku60019, a specific inhibitor of ATM kinase. The phosphorylated cortactin, the target protein of oxidized ATM, was confirmed by immunoprecipitation-western blots and in vitro kinase assay. The functions of phosphorylated cortactin were studied by specific short hairpin RNA, site-directed mutation, transwell assay, and actin polymerization assay. Results: Enhanced oxidized ATM proteins were present not only in the advanced and invasive breast tumor tissues but also malignant hypoxic breast cancer cells, in the absence of DNA damage. Loss of ATM expression or inhibiting oxidized ATM kinase activity reduced breast cancer cell migration and invasion. Using quantitative phosphoproteomics approach, 333 oxidized ATM target proteins were identified, some of these proteins govern key signaling associated with gap junction, focal adhesion, actin cytoskeleton rearrangement. Cortactin, one of the biggest changed phospho-protein, is a novel oxidized ATM-dependent target in response to hypoxia. Mechanically, we reveal that hypoxia-activated ATM can enhance the binding affinity of cortactin with Arp2/3 complex by phosphorylating cortactin at serine 113, and as a result, in favor of breast cancer cell migration and invasion. Conclusion: Oxidized ATM can phosphorylate cortactin at serine 113, playing a critical role in promoting breast tumor cell mobility and invasion via actin polymerization.

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Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.11.1722 ◽

1988 ◽

Vol 6 (11) ◽

pp. 1722-1727 ◽

Cited By ~ 225

Author(s):

W J Curran ◽

M J Kornstein ◽

J J Brooks ◽

A T Turrisi

Keyword(s):

Relapse Rate ◽

Salvage Therapy ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Subtotal Resection ◽

Total Resection ◽

Mediastinal Irradiation ◽

Significant Difference

To evaluate the role of mediastinal irradiation (RT) following surgery for invasive thymomas, a clinical and pathologic review of 117 patients with the diagnosis of thymoma was completed. Fourteen cases were excluded because of the lack of histologic criteria for a thymic tumor, and the remaining 103 were classified according to a staging system as follows: stage I, completely encapsulated (43); stage II, extension through the capsule or pericapsular fat invasion (21); stage III, invasion of adjacent structures (36); and stage IV, thoracic dissemination or metastases (3). The 5-year actuarial survival and relapse-free survival rates were 67% and 100% for stage I, 86% and 58% for stage II, and 69% and 53% for stage III. No recurrences occurred among stage I patients after total resection without RT. However, eight of 21 patients with invasive (stage II or III) thymomas had mediastinal recurrence as the first site of failure following total resection without RT. The 5-year actuarial mediastinal relapse rate of 53% in this group compares unfavorably with the mediastinal relapse rate seen among stage II or III cases following total resection with RT (0%) or following subtotal resection/biopsy with RT (21%). Despite attempted salvage therapy, five of eight patients with mediastinal relapse following total resection alone died of progressive disease. No significant difference was observed in the local relapse rate, overall relapse rate, or survival between those patients undergoing biopsy and RT v subtotal resection and RT for invasive thymomas (stages II and III). Total resection alone appears to be inadequate therapy resulting in an unacceptably high local failure rate with poor salvage therapy results.

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Use of Truquant BR radioimmunoassay for early detection of breast cancer recurrence in patients with stage II and stage III disease.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.6.2322 ◽

1997 ◽

Vol 15 (6) ◽

pp. 2322-2328 ◽

Cited By ~ 71

Author(s):

D W Chan ◽

R A Beveridge ◽

H Muss ◽

H A Fritsche ◽

G Hortobagyi ◽

...

Keyword(s):

Breast Cancer ◽

Predictive Value ◽

Cox Regression ◽

Recurrent Disease ◽

Cancer Recurrence ◽

Stage Ii ◽

Stage Iii ◽

Antigen Test ◽

Cox Regression Analysis ◽

Test Result

PURPOSE The Truquant BR radioimmunoassay (RIA) (Biomira Diagnostics Inc, Rexdale, Canada) uses the monoclonal antibody B27.29 to quantitate the MUC-1 gene product (CA 27.29 antigen) in serum. We evaluated CA 27.29 antigen in a controlled, prospective clinical trial for its ability to predict relapse in stage II and stage III breast cancer patients. PATIENTS AND METHODS Over a 2-year period, 166 patients who had completed therapy for stage II (80.1%) or III (19.9%) breast cancer and were clinically free of disease were serially tested for CA 27.29 antigen levels. The study was double-masked and cancer recurrence was documented based on clinical findings. Patients with two consecutive CA 27.29 antigen test results above the upper limit of normal were considered positive. RESULTS The Truquant BR RIA had a sensitivity of 57.7%, specificity of 97.9%, positive predictive value of 83.3%, and negative predictive value of 92.6%. The recurrence rate was 15.7%. A Cox regression analysis showed that the only variable to correlate with recurrent disease was the CA 27.29 antigen test result. Patients with a positive test result had increased odds of having a recurrence (odds ratio, 6.8; P < .00001). The test was effective in predicting recurrence in patients with both distant and locoregional disease. In a subgroup of patients with bone pain, CA 27.29 antigen level was found to identify reliably patients who would subsequently develop recurrent disease. CONCLUSION These data demonstrate that the Truquant BR RIA can be used as an aid to predict recurrent breast cancer in patients with stage II and III disease.

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Measurement of free and complexed soluble vascular endothelial growth factor receptor, Flt-1, in fluid samples: development and application of two new immunoassays

Clinical Science ◽

10.1042/cs1000567 ◽

2001 ◽

Vol 100 (5) ◽

pp. 567-575 ◽

Cited By ~ 22

Author(s):

Funmi M. BELGORE ◽

Andrew D. BLANN ◽

Gregory Y. LIP

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cell ◽

Growth Factor ◽

Plasma Levels ◽

Biological Significance ◽

Growth Factor Receptor ◽

Soluble Form ◽

Vascular Endothelial ◽

Significant Difference ◽

Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis and enhances vascular permeability. VEGF interacts with the endothelium via two membrane-spanning receptors, fms-like tyrosine kinase (Flt)-1 and kinase domain receptor. A soluble form of Flt-1 (sFlt-1) was isolated from endothelial cell media; however, its biological significance is still unknown, with limited data on plasma sFlt-1 levels in disease states. We have developed two new ELISAs for detecting free and VEGF-complexed sFlt-1, which were tested in accordance with standard validation and assessment methodologies employed in commercial settings. The intra-and inter-assay coefficients of variation are < 5% and 10% respectively, and results are highly reproducible. Applying these ELISAs in a clinical setting, we measured levels of VEGF, free and complexed sFlt-1 in citrated plasma from 40 patients with cardiovascular disease and 40 healthy controls. Median (interquartile range) plasma levels of VEGF in patients were significantly greater than controls [403 pg/ml (158–925 pg/ml) versus 113 pg/ml (33–231 pg/ml), P ⩽ 0.05]. Free sFlt-1 was significantly lower in patients compared with controls [8 ng/ml (2–22 ng/ml) versus 21 ng/ml (10–73 ng/ml), P ⩽ 0.05]. There was no significant difference in the levels of complexed sFlt-1 between the two groups. Plasma levels of VEGF-complexed sFlt-1 are minimal, despite the presence of excess free sFlt-1. Thus unbound plasma VEGF detected by ELISA may represent the majority of circulating VEGF, and justifies the measurement of plasma VEGF as an indicator of circulating VEGF levels. Furthermore, these results suggest that circulating sFlt-1 may serve as a selective inhibitor of VEGF activity, and that this regulatory mechanism may be altered by pathological conditions.

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Report of clinico-pathological features of breast cancer in HIV-infected and uninfected women in Botswana

Infectious Agents and Cancer ◽

10.1186/s13027-019-0245-6 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Rohini K. Bhatia ◽

Mohan Narasimhamurthy ◽

Yehoda M. Martei ◽

Pooja Prabhakar ◽

Jeré Hutson ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Stage Iii ◽

Disease Stage ◽

Breast Cancers ◽

Pathological Features ◽

Breast Cancer Patients ◽

Hiv Status ◽

Receptor Status ◽

Significant Difference

Abstract Background To characterize the clinico-pathological features including estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu (HER2) expression in breast cancers in Botswana, and to compare them by HIV status. Methods This was a retrospective study using data from the National Health Laboratory and Diagnofirm Medical Laboratory in Gaborone from January 1, 2011 to December 31, 2015. Clinico-pathological details of patients were abstracted from electronic medical records. Results A total of 384 unique breast cancer reports met our inclusion criteria. Of the patients with known HIV status, 42.7% (50/117) were HIV-infected. Median age at the time of breast cancer diagnosis was 54 years (IQR 44–66 years). HIV-infected individuals were more likely to be diagnosed before age 50 years compared to HIV-uninfected individuals (68.2% vs 23.8%, p < 0.001). The majority of patients (68.6%, 35/51) presented with stage III at diagnosis. Stage IV disease was not presented because of the lack of data in pathology records surveyed, and additionally these patients may not present to clinic if the disease is advanced. Overall, 68.9% (151/219) of tumors were ER+ or PR+ and 16.0% (35/219) were HER2+. ER+ or PR+ or both, and HER2- was the most prevalent profile (62.6%, 132/211), followed by triple negative (ER−/PR−/HER2-, 21.3%, 45/211), ER+ or PR+ or both, and HER2+, (9.0%, 19/211) and ER−/PR−/HER2+ (7.1%, 15/211). There was no significant difference in receptor status noted between HIV-infected and HIV-uninfected individuals. Conclusions Majority of breast cancer patients in Botswana present with advanced disease (stage III) at diagnosis and hormone receptor positive disease. HIV-infected breast cancer patients tended to present at a younger age compared to HIV-uninfected patients. HIV status does not appear to be associated with the distribution of receptor status in breast cancers in Botswana.

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Detection of bone marrow involvement in breast cancer with magnetic resonance imaging.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.7.1415 ◽

1994 ◽

Vol 12 (7) ◽

pp. 1415-1421 ◽

Cited By ~ 25

Author(s):

S M Sanal ◽

F W Flickinger ◽

M J Caudell ◽

R M Sherry

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Serum Alkaline Phosphatase ◽

Bone Marrow Involvement ◽

Stage Iv ◽

Stage Ii ◽

Stage Iii ◽

Mri Findings ◽

Two Stage ◽

Bone Scans

PURPOSE To evaluate the value of magnetic resonance imaging (MRI) in detecting bone marrow metastases in patients with breast cancer. PATIENTS AND METHODS Twenty-three patients with breast cancer in various stages (stage IV, 11; stage III, five; stage II, seven) were evaluated for bone marrow involvement. MRIs of marrow from lumbar spine, pelvis, and proximal femora were obtained with a 1.5-Tesla unit. All patients underwent bilateral bone marrow aspirations and biopsies for histologic evaluation and immunostaining with monoclonal antibody (MoAB) against low-molecular weight cytokeratin (CAM 5.2). Marrow MRI findings were compared with technetium 99m bone scans. Patients with stage II or III disease were monitored for clinical outcome. Possible correlation of MRI findings with serum alkaline phosphatase level was explored. RESULTS Fourteen of 23 patients showed MRI abnormalities suggestive of metastatic marrow disease (stage IV, nine; stage III, two; stage II, three). In six patients with abnormal MRIs, histology and MoAB immunostaining confirmed marrow involvement (stage IV, five; stage III, zero; stage II, one). In the other eight patients with MRI abnormalities, neither of these methods confirmed the presence of marrow metastasis. Four of five operable breast cancer (stage II-III) patients with an abnormal initial MRI showed additional abnormalities on follow-up examination and developed metastatic disease within 5 to 18 months demonstrable by conventional clinical methods. Conversely, none of the operable patients with negative MRIs developed recurrent disease at 3 to 16 months (Student's t test, P = .01). Nine patients with a normal MRI had no evidence of marrow involvement with histologic or MoAB immunostaining (stage IV, two; stage III, two; stage II, five). Of 14 patients with abnormal MRIs, bone scans were normal in seven and failed to show corresponding abnormalities in six. Elevated serum alkaline phosphatase levels showed a direct relationship with abnormal bone scans indicating extensive bony involvement, but failed to correlate with positive marrow MRIs. CONCLUSION MRI is a promising new technique to detect occult marrow involvement in breast cancer patients. There is a good correlation between abnormal marrow MRI and early development of clinical metastatic disease in patients with stage II to III disease.

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Serum Levels of OPG and MIP-1α in Untreated Multiple Myeloma Patients. Correlations with Staging, Survival and Bone Disease.

Blood ◽

10.1182/blood.v106.11.5074.5074 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5074-5074

Author(s):

Argyro Papadogiannis ◽

Marie-Cristine Kyrtsonis ◽

Theodoros P. Vassilakopoulos ◽

Tatiana Tzenou ◽

Antonios G. Antoniadis ◽

...

Keyword(s):

Bone Disease ◽

Staging System ◽

Serum Levels ◽

High Serum ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Bone Lesions ◽

Disease Biology ◽

Significant Difference

Abstract Cytokines, such as MIP-1a (macrophage inhibiting factor) and OPG (osteoprotegerin) are assumed to play a role in MM disease biology and bone disease, by mechanisms that are still under investigation. MIP-1a is constitutively secreted by myeloma cells, plays a possible role in the development of MM bone lesions, enhance MM cell adhesion to stromal cells and its serum levels have been recently related to survival in MM. OPG is a soluble decoy receptor which acts as a soluble receptor antagonist that prevents osteoclasts activation and the development of bone disease. Reported findings on serum OPG levels in MM patients are controversial as well as its possible role in the biology of the disease. In order to investigate the possible relationship of MIP-1a and OPG levels in MM patients with prognosis and bone disease, we determined by ELISA serum MIP-1a and OPG levels in 20 MGUS, 82 MM patients and 27 healthy individuals (HI). Both cytokines were determined by ELISA (R&D, Quantikine, USA) in frozen sera collected at dignosis, before treatment. The median age of MM patients was 69 years (44–84) and 50% were males. MM patients’ stage was as follows: 23 stage I, 28 stage II, 31 stage III according to Durie-Salmon staging system and 27 stage I, 17 stage II, 35 stage III according to the International Scoring System (ISS). In HI median MIP-1a was 28 pg/ml (15–54) and median OPG 1600 pg/ml (450–4600). In subjects with MGUS, median MIP-1a was 34 pg/ml (17–58) and median OPG 2300 pg/ml (820–6200). In MM patients, median pretreatment serum MIP-1a was 32 pg/ml (16–100) and OPG 3000 pg/ml (820–25000). No statistical significant difference was observed between HI, MGUS and MM patients with regard to MIP-1a levels but for OPG levels differences between HI and MM patients and between MGUS and MM patients were both significant (0.01 and 0.05 respectively). No relationship was found between MIP-1a or OPG levels and bone disease. However, there was a trend for longer survival in patients with MIP-1a or OPG levels lower than median (5-year overall survival 60 ± 12 vs 38 ± 14, p=0.08 and 66 ± 13 vs 29 ± 13, p=0.07 respectively). In addition MIP-1a levels were correlated with ISS stage: MIP-1a levels were 28.3±11.3 in ISS stage 1, 29.8±11.1 in ISS stage 2, 39±19.2 in ISS stage 3 (p=0.02). In conclusion, in our experience serum OPG levels are higher in MM patients than in MGUS or HI, MIP-1a levels are correlated with the ISS stage and both high serum MIP-1a and OPG levels at diagnosis are related with a shorter survival.

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