scholarly journals A Risk Signature with Immune and Inflammatory Cells Infiltration in Gastric Cancer Predicts Survival and Efficiency of Chemotherapy

2020 ◽  
Author(s):  
Sen Li ◽  
Wenpeng Wang ◽  
Pengfei Ma ◽  
Junli Zhang ◽  
Yanghui Cao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
T Lymphocytes ◽  
Risk Stratification ◽  
Validation Cohort ◽  
Risk Group ◽  
Inflammatory Cells ◽  
High Risk Group ◽  
Training Cohort

Abstract Background In order to accurately predict outcomes of gastric cancer (GC), we developed a risk signature with tumor infiltration immune and inflammatory cells for prognosis.Methods A risk signature model in combination with CD66b + neutrophils, CD3 + T, CD8 + T lymphocytes, and FOXP3 + regulatory T cells was developed in a training cohort of 327 GC patients undergoing surgical resection between 2011 and 2012, and validated in a validation cohort of 285 patients from 2012 to 2013.Results High CD66b expression predicted poor disease-special survival (DSS) as well as inversely correlated with CD8 (P < 0.05) and FOXP3 expression (P < 0.05) in the training cohort, comparable disease-free survival (DFS) findings were observed in the validation cohort.Furthermore, a risk stratification was developed from integration of CD66b + neutrophils and T immune cells. In both DFS and DSS, the high-risk group all demonstrated worse prognosis than low-risk group in both the training cohort and the validation cohort (all P < 0.05). In addition, the high-risk group was associated with post-operative relapses. Furthermore, this risk signature model increase the predictive accuracy and efficiency for post-operative relapses. At last, the high-risk group identified a subgroup of GC patients who tend to not benefit from adjuvant chemotherapy.Conclusions Incorporation of neutrophils into T lymphocytes could provide more accurate prognostic information in GC, and this risk stratification predicted survival benefit from post-operative adjuvant chemotherapy in GC.

Identifying an immune-related gene-pair for prognosis prediction of metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Qiqi Zhu ◽  
Du Cai ◽  
Wei Wang ◽  
Min-Er Zhong ◽  
Dejun Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Related Gene ◽  
Training Cohort ◽  
Gene Pairs ◽  
Immune Related Gene

e15565 Background: Few robust predictive biomarkers have been applied in clinical practice due to the heterogeneity of metastatic colorectal cancer (mCRC) . Using the gene pair method, the absolute expression value of genes can be converted into the relative order of genes, which can minimize the influence of the sequencing platform difference and batch effects, and improve the robustness of the model. The main objective of this study was to establish an immune-related gene pairs signature (IRGPs) and evaluate the impact of the IRGPs in predicting the prognosis in mCRC. Methods: A total of 205 mCRC patients containing overall survival (OS) information from the training cohort ( n = 119) and validation cohort ( n = 86) were enrolled in this study. LASSO algorithm was used to select prognosis related gene pairs. Univariate and multivariate analyses were used to validate the prognostic value of the IRGPs. Gene sets enrichment analysis (GSEA) and immune infiltration analysis were used to explore the underlying biological mechanism. Results: An IRGPs signature containing 22 gene pairs was constructed, which could significantly separate patients of the training cohort ( n = 119) and validation cohort ( n = 86) into the low-risk and high-risk group with different outcomes. Multivariate analysis with clinical factors confirmed the independent prognostic value of IRGPs that higher IRGPs was associated with worse prognosis (training cohort: hazard ratio (HR) = 10.54[4.99-22.32], P < 0.001; validation cohort: HR = 3.53[1.24-10.08], P = 0.012). GSEA showed that several metastasis and immune-related pathway including angiogenesis, TGF-β-signaling, epithelial-mesenchymal transition and inflammatory response were enriched in the high-risk group. Through further analysis of the immune factors, we found that the proportions of CD4+ memory T cell, regulatory T cell, and Myeloid dendritic cell were significantly higher in the low-risk group, while the infiltrations of the Macrophage (M0) and Neutrophil were significantly higher in the high-risk group. Conclusions: The IRGPs signature could predict the prognosis of mCRC patients. Further prospective validations are needed to confirm the clinical utility of IRGPs in the treatment decision.

scholarly journals A radiomics nomogram for prediction of overall survival  in hepatocellular carcinoma after hepatectomy

2020 ◽  
Author(s):  
Qinqin Liu ◽  
Jing Li ◽  
Fei Liu ◽  
Weilin Yang ◽  
Jingjing Ding ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Clinicopathological Factors ◽  
Training Cohort ◽  
Texture Parameters ◽  
Radiomics Signature

Abstract Background Hepatocellular carcinoma (HCC) is associated with dismal prognosis, and prediction of the prognosis of HCC can assist the therapeutic decisions. More and more studies showed that the texture parameters of images can reflect the heterogeneity of the tumor, and may have the potential to predict the prognosis of patients with HCC after surgical resection. The aim of the study was to investigate the prognostic value of computed tomography (CT) texture parameters for patients with HCC after hepatectomy, and try to develop a radiomics nomograms by combining clinicopathological factors with radiomics signature.Methods 544 eligible patients were enrolled in the retrospective study and randomly divided into training cohort (n=381) and validation cohort (n=163). The regions of interest (ROIs) of tumor is delineated, then the corresponding texture parameters are extracted. The texture parameters were selected by using the least absolute shrinkage and selection operator (LASSO) Cox model in training cohort, and the radiomics score (Rad-score) was generated. According to the cut-off value of the Rad-score calculated by the receiver operating characteristic (ROC) curve, the patients were divided into high-risk group and low-risk group. The prognosis of the two groups was compared and validated in the validation cohort. Univariate and multivariable analyses by COX proportional hazard regression model were used to select the prognostic factors of overall survival (OS). The radiomics nomogram for OS were established based on the radiomics signature and clinicopathological factors. The Concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to evaluate the performance of the radiomics nomogram.Result 7 texture parameters associated with OS were selected in the training, and the radiomics signature was formulated based on the texture parameters. The patients were divided into high-risk group and low-risk group by the cut-off values of the Rad-score of OS. The 1-, 3- and 5-year OS rate was 71.0%, 45.5% and 35.5% in the high-risk group, respectively, and 91.7%, 82.1% and 78.7%, in the low-risk group, respectively, with significant difference (P <0.001). COX regression model found that Rad-score was an independent prognostic factor of OS. In addition, the radiomics nomogram was developed based on five variables: α‐fetoprotein (AFP), platelet lymphocyte ratio (PLR), largest tumor size, microvascular invasion (MVI) and Rad-score. The nomograms displayed good accuracy in predicting OS (C-index=0.747) in the training cohort and was confirmed in the validation cohort (C-index=0.777). The calibration plots also showed an excellent agreement between the actual and predicted survival probabilities. The DAC indicated that the radiomics nomogram showed better clinical usefulness than the clinicopathologic nomogram.Conclusion The radiomics signature is potential biomarkers of the prognosis of HCC after hepatectomy. Radiomics nomogram that integrated radiomics signature can provide more accurate estimate of OS for patients with HCC after hepatectomy.

scholarly journals Omission of Chemotherapy in HR+/HER2- Early Invasive Breast Cancer Based on Combined 6-IHC Score?

2020 ◽  
Author(s):  
Jiaman Lin ◽  
Zihe Guo ◽  
Shuo Wang ◽  
Xinyu Zheng
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Risk Group ◽  
Disease Free Survival ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Oncotype Dx ◽  
Axillary Lymph ◽  
Training Cohort

Abstract Background: Previous randomized studies have assessed the possibility of omission of chemotherapy in some hormone receptor (HR)-positive and HER2-negative (HR+/HER2-) breast cancers (BC) based on gene profiling test, e.g., Oncotype DX. The goal of this study was to evaluate if combination of six proliferation related biomarkers by immunohistochemistry (6-IHC) could be a cost-effective option in determining the necessity of adjuvant chemotherapy in HR+/HER2- BC.Methods: A retrospective analysis of HR+/HER2- BC patients was conducted in the First Affiliated Hospital of China Medical University from 2010 to 2016. The expression of 6 BC-related proliferation and invasion genes (Cathepsin L2, MMP11, CyclinB1, Aurora A, Survivin and Ki67) from Oncotype DX were analyzed through IHC (designated as 6-IHC). All the included patients were divided randomly at a 7:3 ratio into training and testing cohorts. The cutoff prognosis index (PI) of 6-IHC was determined by multivariate Cox risk regression analysis after calculating the PI of each patient in training cohort and confirmed in testing cohort. The patients were classified into “Low” and “High” risk groups based on the PI value. Kaplan-Meier (KM) method was used to analyze Disease-free survival (DFS) and overall survival (OS). 6-IHC score and other factors associated with survival benefit of adjuvant chemotherapy were compared with Ki67 index.Results: A total of 330 patients were included and divided into training cohort (n = 231) and validation cohort (n = 99). The receiver operating characteristic (ROC) curve analysis showed that the patients can be divided into 6-IHC score “High” and “Low” risk groups using the cut-off PI of 2.16. The 8-year DFS and OS were 54.6% and 69.2%, respectively in the 6-IHC score “High” risk group; 85.5% and 92.5%, respectively in the 6-IHC score “Low” risk group. The 8-year DFS and OS were 70.8% and 80.9%, respectively in the Ki67 “High” risk group, 77.7% and 87.6%, respectively in the Ki67 “Low” risk group. The KM curves showed that chemotherapy did not significantly improve the DFS in the 6-IHC score “Low” risk group (p = 0.830), but significantly improved the DFS in the 6-IHC score “High” risk group (P = 0.012).Conclusions: Combined 6-IHC score could be a reliable tool in predicting cancer-specific recurrences and survival in HR+/HER2- BC patients and identifying patients who could benefit from adjuvant chemotherapy regardless of the involvement of axillary lymph node (ALN).

scholarly journals Circulating Plasma Cells as a Biomarker to Predict Newly Diagnosed Multiple Myeloma Prognosis: Developing Nomogram Prognostic Models

2021 ◽  
Vol 11 ◽  
Author(s):  
Qianwen Cheng ◽  
Li Cai ◽  
Yuyang Zhang ◽  
Lei Chen ◽  
Yu Hu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Plasma Cells ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Newly Diagnosed ◽  
Training Cohort ◽  
Entire Cohort

Background: To investigate the prognostic value of circulating plasma cells (CPC) and establish novel nomograms to predict individual progression-free survival (PFS) as well as overall survival (OS) of patients with newly diagnosed multiple myeloma (NDMM).Methods: One hundred ninetyone NDMM patients in Wuhan Union Hospital from 2017.10 to 2020.8 were included in the study. The entire cohort was randomly divided into a training (n = 130) and a validation cohort (n = 61). Univariate and multivariate analyses were performed on the training cohort to establish nomograms for the prediction of survival outcomes, and the nomograms were validated by calibration curves.Results: When the cut-off value was 0.038%, CPC could well distinguish patients with higher tumor burden and lower response rates (P &lt; 0.05), and could be used as an independent predictor of PFS and OS. Nomograms predicting PFS and OS were developed according to CPC, lactate dehydrogenase (LDH) and creatinine. The C-index and the area under receiver operating characteristic curves (AUC) of the nomograms showed excellent individually predictive effects in training cohort, validation cohort or entire cohort. Patients with total points of the nomograms ≤ 60.7 for PFS and 75.8 for OS could be defined as low-risk group and the remaining as high-risk group. The 2-year PFS and OS rates of patients in low-risk group was significantly higher than those in high-risk group (p &lt; 0.001).Conclusions: CPC is an independent prognostic factor for NDMM patients. The proposed nomograms could provide individualized PFS and OS prediction and risk stratification.

scholarly journals A Novel Nomogram including AJCC Stages Could Better Predict Survival for NSCLC Patients Who Underwent Surgery: A Large Population-Based Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiaoling Shang ◽  
Haining Yu ◽  
Jiamao Lin ◽  
Zhenxiang Li ◽  
Chenglong Zhao ◽  
...  
Keyword(s):  
High Risk ◽  
Lymph Nodes ◽  
Classification System ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Training Cohort ◽  
Ajcc Stage ◽  
Nsclc Patients ◽  
Positive Lymph Nodes

Objective. In this study, we aimed to establish a novel nomogram model which was better than the current American Joint Committee on Cancer (AJCC) stage to predict survival for non-small-cell lung cancer (NSCLC) patients who underwent surgery. Patients and Methods. 19617 patients with initially diagnosed NSCLC were screened from Surveillance Epidemiology and End Results (SEER) database between 2010 and 2015. These patients were randomly divided into two groups including the training cohort and the validation cohort. The Cox proportional hazard model was used to analyze the influence of different variables on overall survival (OS). Then, using R software version 3.4.3, we constructed a nomogram and a risk classification system combined with some clinical parameters. We visualized the regression equation by nomogram after obtaining the regression coefficient in multivariate analysis. The concordance index (C-index) and calibration curve were used to perform the validation of nomogram. Receiver operating characteristic (ROC) curves were used to evaluate the clinical utility of the nomogram. Results. Univariate and multivariate analyses demonstrated that seven factors including age, sex, stage, histology, surgery, and positive lymph nodes (all, P<0.001) were independent predictors of OS. Among them, stage (C-index = 0.615), positive lymph nodes (C-index = 0.574), histology (C-index = 0.566), age (C-index = 0.563), and sex (C-index = 0.562) had a relatively strong ability to predict the OS. Based on these factors, we established and validated the predictive model by nomogram. The calibration curves showed good consistency between the actual OS and predicted OS. And the decision curves showed great clinical usefulness of the nomogram. Then, we built a risk classification system and divided NSCLC patients into two groups including high-risk group and low-risk group. The Kaplan–Meier curves revealed that OS in the two groups was accurately differentiated in the training cohort (P<0.001). And then, we validated this result in the validation cohort which also showed that patients in the high-risk group had worse survival than those in the low-risk group. Conclusion. The results proved that the nomogram model had better performance to predict survival for NSCLC patients who underwent surgery than AJCC stage. These tools may be helpful for clinicians to evaluate prognostic indicators of patients undergoing operation.

scholarly journals Pre-hospital risk assessment in suspected non-ST-elevation acute coronary syndrome: A prospective observational study

2018 ◽  
Vol 9 (1_suppl) ◽  
pp. 5-12 ◽  
Author(s):  
Dominique N van Dongen ◽  
Rudolf T Tolsma ◽  
Marion J Fokkert ◽  
Erik A Badings ◽  
Aize van der Sluis ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Heart Score ◽  
Coronary Syndrome ◽  
Risk Patients ◽  
St Elevation

Background: Pre-hospital risk stratification of non-ST-elevation acute coronary syndrome (NSTE-ACS) by the complete HEART score has not yet been assessed. We investigated whether pre-hospital risk stratification of patients with suspected NSTE-ACS using the HEART score is accurate in predicting major adverse cardiac events (MACE). Methods: This is a prospective observational study, including 700 patients with suspected NSTE-ACS. Risk stratification was performed by ambulance paramedics, using the HEART score; low risk was defined as HEART score ⩽ 3. Primary endpoint was occurrence of MACE within 45 days after inclusion. Secondary endpoint was myocardial infarction or death. Results: A total of 172 patients (24.6%) were stratified as low risk and 528 patients (75.4%) as intermediate to high risk. Mean age was 53.9 years in the low risk group and 66.7 years in the intermediate to high risk group ( p<0.001), 50% were male in the low risk group versus 60% in the intermediate to high risk group ( p=0.026). MACE occurred in five patients in the low risk group (2.9%) and in 111 (21.0%) patients at intermediate or high risk ( p<0.001). There were no deaths in the low risk group and the occurrence of acute myocardial infarction in this group was 1.2%. In the high risk group six patients died (1.1%) and 76 patients had myocardial infarction (14.4%). Conclusions: In suspected NSTE-ACS, pre-hospital risk stratification by ambulance paramedics, including troponin measurement, is accurate in differentiating between low and intermediate to high risk. Future studies should investigate whether transportation of low risk patients to a hospital can be avoided, and whether high risk patients benefit from immediate transfer to a hospital with early coronary angiography possibilities.

Helicobacter pylori Eradication Prevents Extension of Intestinalization Even in the High-Risk Group for Gastric Cancer

Digestion ◽  
2010 ◽  
Vol 81 (4) ◽  
pp. 223-230 ◽  
Author(s):  
Akiko Shiotani ◽  
Ryuji Nishi ◽  
Noriya Uedo ◽  
Hiroyasu Iishi ◽  
Hideaki Tsutsui ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Helicobacter Pylori Eradication

scholarly journals Pre-Enucleation Chemotherapy in Advanced Intraocular Retinoblastoma. Central America Follow Up: AHOPCA II

2016 ◽  
Vol 2 (3_suppl) ◽  
pp. 75s-75s
Author(s):  
Sandra Luna-Fineman ◽  
Soad L. Alabi ◽  
Mauricio E. Castellanos ◽  
Yessika Gamboa ◽  
Ligia Fu ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Central America ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
High Risk Group ◽  
Globe Rupture ◽  
Neo Adjuvant Chemotherapy ◽  
Standard Risk

Abstract 57a Purpose: A significant percentage of patients in Central America present with buphthalmos, carrying a high risk of globe rupture and orbital contamination. In 2007, AHOPCA introduced chemotherapy before enucleation in children with buphthalmos. Methods: Patients with advanced intraocular disease were considered standard-risk and underwent enucleation. Those with diffuse invasion of choroid, postlaminar optic nerve, or anterior chamber invasion received 4-6 cycles of adjuvant chemotherapy (vincristine, carboplatin, etoposide). Patients with buphthalmos or perceived to be at risk for abandonment were considered high-risk, given 2-3 cycles of chemotherapy before enucleation to compete 6 cycles regardless of pathology. All cases were discussed via online meetings. Results: From 2007 to 2014, 396 patients were enrolled; 240 had IRSS stage I (174 unilateral). 143 had upfront enucleation, 95 had pre-enucleation chemotherapy, 1 is pending enucleation and 1 abandoned before enucleation. The standard-risk group 69 had risk pathology and 76 had no risk factors; 125 had no events, 5 abandoned 11 relapsed/progressed and 2 died of toxicity. Of 95 high-risk group, 8 abandoned, 20 relapse/progressive, 6 had toxic deaths and 61 are alive at last follow-up (median time of 4 years). Of high risk group, 55 were unilateral, 82% are alive. At 7 years OS (abandonment-censored) was 95±0.02 and 79±0.04 for standard-risk and high-risk (p=0.008). Conclusion: AHOPCA addressed advanced intraocular disease with an innovative approach. In eyes with buphthalmos and patients with risk of abandonment, neo-adjuvant chemotherapy is effective, when followed by post-enucleation chemotherapy. This approach avoids ocular rupture and intensified therapy, and reduces refusal/abandonment rate. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.

scholarly journals Adnexal mass risk assessment: a multivariate index assay for malignancy risk stratification

2019 ◽  
Vol 15 (33) ◽  
pp. 3783-3795
Author(s):  
Zhen Zhang ◽  
Rowan G Bullock ◽  
Herbert Fritsche
Keyword(s):  
Risk Assessment ◽  
High Risk ◽  
Risk Stratification ◽  
Predictive Value ◽  
Adnexal Mass ◽  
Clinical Performance ◽  
Risk Group ◽  
High Risk Group ◽  
Adnexal Masses ◽  
Immediate Surgery

Aims: Adnexal mass risk assessment (AMRA) stratifies patients with adnexal masses, identifying the relatively small number of malignancies from benigns which might take a ‘watchful waiting’ approach. Methods: AMRA uses seven biomarkers and derived from women with adnexal masses scheduled for surgery. Estimated clinical performance was calculated using fixed prevalence. Results: At 5% prevalence, the high-risk group, 7.9% total, captured 75.9% of invasive malignancies at a positive predictive value of 35.8%. High risk/intermediate risk combined had a sensitivity of 89.7 and 95.6% for pre- and post-menopausal cancers, respectively. The low-risk group, 67.8% total, had an negative predictive value of 99.0%. Conclusion: With highly differentiating risk stratification capability across histological subtypes and stages, AMRA is potentially applicable to patients with adnexal masses to assist deciding whether immediate surgery is recommended.

Validation of a Novel Tissue Array Based Classification of Multiple Myeloma (MM).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1671-1671
Author(s):  
Nizar J Bahlis ◽  
Alex Klimowicz ◽  
Paola Neri ◽  
Anthony Magliocco ◽  
Douglas A. Stewart ◽  
...  
Keyword(s):  
High Risk ◽  
Validation Cohort ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Protein Array ◽  
Immunoperoxidase Staining ◽  
Initial Testing ◽  
Independent Validation

Abstract Background: Gene expression profiling molecular classification of MM was proven to be an independent predictor of survival post autologous stem cell transplant (ASCT); however it had limited clinical applicability due to its complex methodology and high costs. We have previously reported the results of a protein-array based classification of MM in an initial testing cohort and concluded that positive immunoperoxidase staining for FGFR3, Cyclin B2 or Integrin beta7 correlates with a shortened survival post ASCT (Bahlis et al. Blood2007:110:449a). We now report on the results of this TMA classification in a larger and independent validation cohort. Methods: Immunoperoxidase staining for Cyclins B1, B2, D1, D2 and D3, FGFR3, PAX5 and Integrin beta 7 were previously validated in our initial testing cohort (n=52). Further analysis of our initial testing cohort identified 3 risk groups: positive expression of FGFR3 or Integrin beta 7 defined as “High risk”, positive Cyclin B2 (in the absence of FGFR3 or Integrin beta 7) as “Intermediate risk” and the lack of expression of any of these biomarkers defined as “Low risk”. In order to confirm the predictive value of our proposed protein-array classification, these immunohistochemical (IHC) stains were performed on the bone marrow biopsies of a larger and independent validation cohort of 79 newly diagnosed MM patients uniformly treated with a dexamethasone based regimen followed by ASCT. The clinical parameters, response criteria and survival outcomes (TTP and OS) of this validation cohort were defined according to the international uniform response criteria. For IHC analysis two pathologists who were blinded with regards to the clinical outcome of these patients scored the cases independently as positive or negative. Discordance in their scoring was seen in 20/79 (25.7%) with a consensus scoring reassigned to all of these cases. The Kaplan-Meier method was used to estimate OS and TTP. Multivariate analysis was performed using the Cox regression method. Figure Figure Results: 79 patients were included in this validation cohort, the median age was 54.4 yrs (27.9–71), 23.7% had ISS stage III, median beta 2-microglobulin was 3.29 mg/L (1.16–37.5). Del13q and t(4;14) were detected by FISH in 35.6% and 13.6% of patients, respectively. Post ASCT, 68% achieved a CR or VGPR with an overall median TTP and OS of 2.29 years (CI 1.84–2.73) and 5.74 years (CI 4.98–6.51) respectively. Expression of FGFR3 was detected in 7.6% of the patients, cyclin B2 in 58.2% and integrin-beta7 in 17.7%. In univariate analysis expression of FGFR3 was associated with a significantly shorter TTP (P=0.011) but not OS (P=0.114). Similarly integrin-beta7 predicted for a shorter TTP (P=0.008) but not OS (P=0.570). Cyclin B2 also predicted for worse TTP (P=0.047) but not OS (P=0.098), whereas the expression of cyclins D1, D2, D3 and PAX5 did not affect survival. Based on our testing cohort definition of risk groups, 18/79 (22.8%) were considered as “High risk” with significantly shorter TTP 0.93 years (CI 0.74–1.12) compared to 2.29 years (CI 1.88–2.69) and 3.35 years (CI 2.51–4.19) for the “Intermediate” (34/79; 43%) and “Low” (27/79; 34.2%) risk groups respectively (P=0.002). The 5-years estimates for OS was 57.1% for the High-risk group compared to 66.3% and 71.6% for the Intermediate and Low risk group respectively (P=0.258). Multivariate analysis was performed using ISS, del13q and the TMA risk group classification as variables. The TMA classification and del 13q were the only independent predictors of TTP with the high-risk group having 3.4 fold greater risk of relapse (P=0.001). Conclusion: We have validated our protein array based classification of Multiple Myeloma and confirmed its survival predictive value post ASCT. MM patients with the High-risk signature should be spared the toxicity of ASCT and considered instead for other frontline novel therapeutic agents.

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