scholarly journals Prognostic Value of Drug Targets Predicted using Deep Bioinformatic Analysis of M6A-associated lncRNA-based Pancreatic Cancer Model Characteristics and its Tumour Microenvironment

Author(s):  
Peng-wei Cao ◽  
Lei Liu ◽  
Zi-Han Li ◽  
Feng Cao ◽  
Fu-Bao Liu

Abstract Background: The role of N6-methyladenosine (m6A)-associated long-stranded non-coding RNA (lncRNA) in pancreatic cancer is unclear. Therefore, we analysed the characteristics and tumour microenvironment in pancreatic cancer and determined the value of m6A-related lncRNAs for prognosis and drug target prediction.Methods: An m6A-lncRNA co-expression network was constructed using The Cancer Genome Atlas database to screen m6A-related lncRNAs. Prognosis-related lncRNAs were screened using univariate Cox regression; patients were divided into high- and low-risk groups and randomised into training and test groups. In the training group, least absolute shrinkage and selection operator (LASSO) was used for regression analysis and to construct a prognostic model, which was validated in the test group. Tumour mutational burden (TMB), immune evasion, and immune function of risk genes were analysed using R; drug sensitivity and potential drugs were examined using the Genomics of Drug Sensitivity in Cancer database.Results: We screened 129 m6A-related lncRNAs; 17 prognosis-related m6A-related lncRNAs were obtained using multivariate analysis and three m6A-related lncRNAs (AC092171.5, MEG9, AC002091.1) were screened using LASSO regression. Survival rates were significantly higher (P < 0.05) in the low-risk than in the high-risk group. Risk score was an independent predictor affecting survival (P < 0.001), with the highest risk score being obtained by calculating the c-index. The TMB significantly differed between the high- and low-risk groups (P < 0.05). In the high- and low-risk groups, mutations were detected in 61 of 70 samples and 49 of 71 samples, respectively, with KRAS, TP53, and SMAD4 showing the highest mutation frequencies in both groups. A lower survival rate was observed in patients with a high versus low TMB. Immune function HLA, Cytolytic activity, and Inflammation-promoting, T cell co-inhibition, Check-point, and T cell co-stimulation significantly differed in different subgroups (P < 0.05). Immune evasion scores were significantly higher in the high-risk group than in the low-risk group. Eight sensitive drugs were screened: ABT.888, ATRA, AP.24534, AG.014699, ABT.263, axitinib, A.443654, and A.770041.Conclusions: We screened m6A-related lncRNAs using bioinformatics, constructed a prognosis-related model, explored TMB and immune function differences in pancreatic cancer, and identified potential therapeutic agents, providing a foundation for further studies of pancreatic cancer diagnosis and treatment.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Morten Lindhardt ◽  
Nete Tofte ◽  
Gemma Currie ◽  
Marie Frimodt-Moeller ◽  
Heiko Von der Leyen ◽  
...  

Abstract Background and Aims In the PRIORITY study, it was recently demonstrated that the urinary peptidome-based classifier CKD273 was associated with increased risk for progression to microalbuminuria. As a prespecified secondary outcome, we aim to evaluate the classifier CKD273 as a determinant of relative reductions in eGFR (CKD-EPI) of 30% and 40% from baseline, at one timepoint without requirements of confirmation. Method The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) is the first prospective observational study to evaluate the early detection of diabetic kidney disease in subjects with type 2 diabetes (T2D) and normoalbuminuria using the CKD273 classifier. Setting 1775 subjects from 15 European sites with a mean follow-up time of 2.6 years (minimum of 7 days and a maximum of 4.3 years). Patients Subjects with T2D, normoalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants were stratified into high- or low-risk groups based on their CKD273 score in a urine sample at screening (high-risk defined as score &gt; 0.154). Results In total, 12 % (n = 216) of the subjects had a high-risk proteomic pattern. Mean (SD) baseline eGFR was 88 (15) ml/min/1.73m2 in the low-risk group and 81 (17) ml/min/1.73m2 in the high-risk group (p &lt; 0.01). Baseline median (interquartile range) urinary albumin to creatinine ratio (UACR) was 5 (3-8) mg/g and 7 (4-12) mg/g in the low-risk and high-risk groups, respectively (p &lt; 0.01). A 30 % reduction in eGFR from baseline was seen in 42 (19.4 %) subjects in the high-risk group as compared to 62 (3.9 %) in the low-risk group (p &lt; 0.0001). In an unadjusted Cox-model the hazard ratio (HR) for the high-risk group was 5.7, 95 % confidence interval (CI) (3.9 to 8.5; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 5.2, 95 % CI (3.4 to 7.8; p&lt;0.0001). A 40 % reduction in eGFR was seen in 15 (6.9 %) subjects in the high-risk group whereas 22 (1.4 %) in the low-risk group developed this endpoint (p&lt;0.0001). In an unadjusted Cox-model the HR for the high-risk group was 5.0, 95 % CI (2.6 to 9.6; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 4.8, 95 % CI (2.4 to 9.7; p&lt;0.0001). Conclusion In normoalbuminuric subjects with T2D, the urinary proteomic classifier CKD273 predicts renal function decline of 30 % and 40 %, independent of baseline eGFR and albuminuria.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Jianfeng Zheng ◽  
Benben Cao ◽  
Xia Zhang ◽  
Zheng Niu ◽  
Jinyi Tong

Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune-related lncRNAs (IRLs) of CC has never been reported. This study is aimed at establishing an IRL signature for patients with CC. A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson correlation analysis between the immune score and lncRNA expression ( p < 0.01 ). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values ( p < 0.05 ) were identified which demonstrated an ability to stratify patients into the low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low-risk group showed longer overall survival (OS) than those in the high-risk group in the training set, valid set, and total set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four-IRL signature in predicting the one-, two-, and three-year survival rates was larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four IRLs in the development of CC were ascertained preliminarily.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 394-394
Author(s):  
Lavanniya Kumar Palani Velu ◽  
Vishnuvardhan Chandrabalan ◽  
Ross Carter ◽  
Colin McKay ◽  
Donald McMillan ◽  
...  

394 Background: Pancreas-specific complications (PSC), comprising postoperative pancreatic fistula, post-pancreatectomy haemorrhage, and intra-abdominal collections, are drivers of morbidity following pancreaticoduodenectomy (PD). Intra-operatively derived pancreatic gland texture is a major determinant of postoperative PSC. We have previously demonstrated that a postoperative day 0 (PoD0) serum amylase ≥ 130 IU/L is an objective surrogate of pancreatic texture, and is associated with PSC. We sought to refine the PSC risk prediction model by including serial measurements of serum C-reactive protein (CRP). Methods: 230 consecutive patients undergoing PD between 2008 and 2014 were included in the study. Routine serum investigations, including amylase and CRP were performed from the pre-operative day. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold value of serum CRP associated with clinically significant PSC. Results: 95 (41.3%) patients experienced a clinically significant PSC. ROC analysis identified post-operative day 2 (PoD2) serum CRP of 180 mg/L as the optimal threshold (P=0.005) associated with clinically significant PSC, a prolonged stay in critical care (P =0.032), and a relaparotomy (P = 0.045). Patients with a PoD0 serum amylase ≥ 130 IU/L who then developed a PoD2 serum CRP ≥ 180 mg/L had a higher incidence of postoperative complications. Patients were categorised into high, intermediate and low risk groups based on PoD0 serum amylase and PoD2 serum CRP. Patients in the high risk group (PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l) had significantly higher incidence of PSC, a return to theatre, prolonged lengths stay (all P≤ 0.05) and a four-fold increase in perioperative mortality compared patients in the intermediate and low risk groups (7 deaths in the high risk group versus 2 and nil in the intermediate and low risk groups respectively). Conclusions: A high risk profile, defined as PoD0 serum amylase ≥ 130 IU/L and PoD2 serum CRP ≥ 180 mg/l, should raise the clinician’s awareness of the increased risk of clinically significant PSC and a complicated postoperative course following pancreaticoduodenectomy.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 186-186 ◽  
Author(s):  
Inhye E. Ahn ◽  
Xin Tian ◽  
Maher Albitar ◽  
Sarah E. M. Herman ◽  
Erika M. Cook ◽  
...  

Abstract Introduction: We previously reported a prognostic scoring system in CLL using pre-treatment factors in patients treated with ibrutinib [Ahn et al, 2016 ASH Annual Meeting]. Here we present long-term follow-up results and validation of the prognostic models in a large independent cohort of patients. We also determine the incidence of resistance-conferring mutations in BTK and PLCG2 genes in different clinical risk groups. Methods and Patients: The discovery cohort comprised 84 CLL patients on a phase II study with either TP53 aberration (deletion 17p or TP53 mutation) or age ≥65 years (NCT01500733). The validation cohort comprised 607 patients pooled from four phase II and III studies for ibrutinib in treatment-naïve or relapsed/refractory CLL (NCT01105247; NCT01578707; NCT01722487; NCT01744691). All patients received single-agent ibrutinib 420mg once daily. We used Cox regression models to identify independent predictors of PFS, Kaplan-Meier method to estimate probabilities of PFS, log-rank test to compare PFS, and Cochran-Armitage trend test to compare the incidence of mutation among subgroups. We used R version 3.5.0 or SAS® version 9.3 for statistical analyses. For biomarker correlation, we tested cellular DNA or cell-free DNA collected from patients in the discovery cohort with the targeted sequencing of BTK and PLCG2 genes. Result: At a median follow-up of 5.2 years, 28 (33.3%) of 84 patients in the discovery cohort progressed or died. 52 (61.9%) patients had treatment-naïve CLL. Independent factors of PFS on univariate analysis were; TP53 aberration, prior treatment, and β-2 microglobulin (B2M) >4mg/L (P<0.05 for all tests). Unmutated IGHV and advanced Rai stage (III/IV) showed a trend toward inferior outcome without reaching statistical significance. Because higher levels of B2M were associated with relapsed/refractory CLL, we performed two multivariate Cox regression models to assess B2M and prior treatment status separately. Risk groups were determined by the presence of TP53 aberration, advanced Rai stage, and B2M >4mg/L for Model 1, and TP53 aberration, advanced Rai stage, and relapsed/refractory CLL for Model 2 (Table 1). The high-risk group had all three adverse risk factors; the intermediate-risk group had two risk factors; and the low-risk group, none or one. The median PFS of the high-risk group was 38.9 months for Model 1 and 38.4 months for Model 2, and was significantly shorter than those of intermediate and low-risk groups. In the validation cohort, 254 (41.8%) of 607 patients progressed or died at a median follow-up of 4.2 years. 167 (27.5%) patients had treatment-naïve CLL. Both models showed statistically significant differences in PFS by risk groups (Table 1). For the high-risk group, 4-year PFS was 30.2% in Model 1 and 30.5% in Model 2, which were inferior to those of intermediate (53.4 and 52.4%) and low-risk groups (68.7 and 73.7%). Model 1 classified 20% of patients and Model 2 classified 28% of patients to the high-risk group. BTK and PLCG2 mutations are common genetic drivers of ibrutinib resistance in CLL. To determine whether the incidence of these mutations correlates with prognostic risk groups, we performed targeted sequencing of BTK and PLCG2 of samples collected from patients in the discovery cohort. We used cell-free DNA for patients who received long-term ibrutinib (≥3 years) and had low circulating tumor burden, and cellular DNA, for samples collected within 3 years on ibrutinib or at progression. Of 84 patients, 69 (82.1%) were tested at least once, and 37 (44.0%) were tested at least twice. The frequency of testing was similar across the risk groups by two models (P>0.05). The cumulative incidences of mutations at 5 years in the low-, intermediate-, and high-risk groups were: 21.4%, 44.8% and 50%, respectively, by Model 1 (P=0.02); and 22.6%, 41.4% and 66.7%, respectively, by Model 2 (P=0.01). Conclusion: We developed and validated prognostic models to predict the risk of disease progression or death in CLL patients treated with ibrutinib. Risk groups classified by three commonly available pre-treatment factors showed statistically significant differences in PFS. The clinically-defined high-risk disease was linked to higher propensity to develop clonal evolution with BTK and/or PLCG2 mutations, which heralded ibrutinib resistance. Disclosures Albitar: Neogenomics Laboratories: Employment. Ma:Neogenomics Laboratories: Employment. Ipe:Pharmacyclics, an AbbVie Company: Employment, Other: Travel; AbbVie: Equity Ownership. Tsao:Pharmacyclics LLC, an AbbVie Company: Employment. Cheng:Pharmacyclics LLC, an AbbVie Company: Employment. Dean:CTI BioPharma Corp.: Employment, Equity Ownership; Pharmacyclics LLC, an AbbVie Company: Employment, Equity Ownership. Wiestner:Pharmacyclics LLC, an AbbVie Company: Research Funding.


2020 ◽  
Author(s):  
Jiaman Lin ◽  
Zihe Guo ◽  
Shuo Wang ◽  
Xinyu Zheng

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).


Author(s):  
Xinshuang Yu ◽  
Peng Dong ◽  
Yu Yan ◽  
Fengjun Liu ◽  
Hui Wang ◽  
...  

Pancreatic cancer is a highly aggressive disease with poor prognosis. N6-methyladenosine (m6A) is critical for post-transcriptional modification of messenger RNA (mRNA) and long non-coding RNA (lncRNA). However, the m6A-associated lncRNAs (m6A-lncRNA) and their values in predicting clinical outcomes and immune microenvironmental status in pancreatic cancer patients remain largely unexplored. This study aimed to evaluate the importance of m6A-lncRNA and established a m6A-lncRNA signature for predicting immunotherapeutic response and prognosis of pancreatic cancer. The m6A-lncRNA co-expression networks were constructed using data from the TCGA and GTEx database. Based on the least absolute shrinkage and selection operator (LASSO) analysis, we constructed an 8 m6A-lncRNA signature risk model, and selection operator (LASSO) analysis, and stratified patients into the high- and low-risk groups with significant difference in overall survival (OS) (HR = 2.68, 95% CI = 1.74–4.14, P &lt; 0.0001). Patients in the high-risk group showed significantly reduced OS compared to patients in the low-risk group (P &lt; 0.001). The clinical characteristics and m6A-lncRNA risk scores were used to construct a nomogram which accurately predicted the OS in pancreatic cancer. TIMER 2.0 were used to investigate tumor immune infiltrating cells and its relationship with pancreatic cancer. CIBERSORT analysis revealed increased higher infiltration proportions of M0 and M2 macrophages, and lower infiltration of naive B cell, CD8+ T cell and Treg cells in the high-risk group. Compared to the low-risk group, functional annotation using ssGSEA showed that T cell infiltration and the differential immune-related check-point genes are expressed at low level in the high-risk group (P &lt; 0.05). In summary, our study constructed a novel m6A-associated lncRNAs signature to predict immunotherapeutic responses and provided a novel nomogram for the prognosis prediction of pancreatic cancer.


2021 ◽  
Author(s):  
Chen-jie Qiu ◽  
Xue-bing Wang ◽  
Zi-ruo Zheng ◽  
Chao-zhi Yang ◽  
Kai Lin ◽  
...  

Abstract Background: The purpose of this study was to identify ferroptosis-related genes (FRGs) associated with the prognosis of pancreatic cancer and to construct a prognostic model based on FRGs. Methods: Based on pancreatic cancer data obtained from The Cancer Genome Atlas database, we established the prognostic model from 232 FRGs. A nomogram was constructed by combining the prognostic model and clinicopathological features. Gene Expression Omnibus datasets and tissue samples obtained from our center were utilized to validate the model. Relationship between risk score and immune cell infiltration was explored by CIBERSORT and TIMER.Results: The prognostic model was established based on four FRGs (ENPP2, ATG4D, SLC2A1 and MAP3K5) and can be an independent risk factor in pancreatic cancer (HR 1.648, 95% CI 1.335-2.035, p < 0.001). Based on the median risk score, patients were divided into a high-risk group and a low-risk group. The prognosis of the low-risk group was significantly better than that of the high-risk group. In the high-risk group, patients treated with chemotherapy had a better prognosis. The nomogram showed that the model was the most important element. Gene set enrichment analysis identified three key pathways, namely, TGFβ signaling, HIF signaling pathway and adherens junction. The prognostic model can also affect the immune cell infiltration, such as macrophages M0, M1, CD4+T cell and CD8+T cell. Conclusion: A ferroptosis-related prognostic model can be employed to predict the prognosis of pancreatic cancer. Ferroptosis can be an important marker and immunotherapy can be a potential therapeutic target for pancreatic cancer.


2021 ◽  
Author(s):  
Jinlong Huo ◽  
Shuang Shen ◽  
Chen Chen ◽  
Rui Qu ◽  
Youming Guo ◽  
...  

Abstract Background: Breast cancer(BC) is the most common tumour in women. Hypoxia stimulates metastasis in cancer and is linked to poor patient prognosis.Methods: We screened prognostic-related lncRNAs(Long Non-Coding RNAs) from the Cancer Genome Atlas (TCGA) data and constructed a prognostic signature based on hypoxia-related lncRNAs in BC.Results: We identified 21 differentially expressed lncRNAs associated with BC prognosis. Kaplan Meier survival analysis indicated a significantly worse prognosis for the high-risk group(P<0.001). Moreover, the ROC-curve (AUC) of the lncRNAs signature was 0.700, a performance superior to other traditional clinicopathological characteristics. Gene set enrichment analysis (GSEA) showed many immune and cancer-related pathways and in the low-risk group patients. Moreover, TCGA revealed that functions including activated protein C (APC)co-inhibition, Cinnamoyl CoA reductase(CCR),check-point pathways, cytolytic activity, human leukocyte antigen (HLA), inflammation-promotion, major histocompatibility complex(MHC) class1, para-inflammation, T cell co-inhibition, T cell co-stimulation, and Type Ⅰ and Ⅱ Interferons (IFN) responses were significantly different in the low-risk and high-risk groups. Immune checkpoint molecules such as ICOS, IDO1, TIGIT, CD200R1, CD28, PDCD1(PD-1), were also expressed differently between the two risk groups. The expression of m6A-related mRNA indicated that YTHDC1, RBM15, METTL3, and FTO were significantly between the high and low-risk groups.Additionally, immunotherapy in patients with BC from the low-risk group yielded a higher frequency of clinical responses to anti-PD-1/PD-L1 therapy or a combination of anti-PD-1/PD-L1and anti-CTLA4 therapies.Except for lapatinib, the results also show that a high-risk score is related to a higher half-maximal inhibitory concentration (IC50) of chemotherapy drugs.Conclusion: A novel hypoxia-related lncRNAs signature may serve as a prognostic model for BC.


Author(s):  
Junyu Huo ◽  
Jinzhen Cai ◽  
Ge Guan ◽  
Huan Liu ◽  
Liqun Wu

Background: Due to the heterogeneity of tumors and the complexity of the immune microenvironment, the specific role of ferroptosis and pyroptosis in hepatocellular carcinoma (HCC) is not fully understood, especially its impact on prognosis.Methods: The training set (n = 609, merged by TCGA and GSE14520) was clustered into three subtypes (C1, C2, and C3) based on the prognosis-related genes associated with ferroptosis and pyroptosis. The intersecting differentially expressed genes (DEGs) among C1, C2, and C3 were used in univariate Cox and LASSO penalized Cox regression analysis for the construction of the risk score. The median risk score served as the unified cutoff to divide patients into high- and low-risk groups.Results: Internal (TCGA, n = 370; GSE14520, n = 239) and external validation (ICGC, n = 231) suggested that the 12-gene risk score had high accuracy in predicting the OS, DSS, DFS, PFS, and RFS of HCC. As an independent prognostic indicator, the risk score could be applicable for patients with different clinical features tested by subgroup (n = 26) survival analysis. In the high-risk patients with a lower infiltration abundance of activated B cells, activated CD8 T cells, eosinophils, and type I T helper cells and a higher infiltration abundance of immature dendritic cells, the cytolytic activity, HLA, inflammation promotion, and type I IFN response in the high-risk group were weaker. The TP53 mutation rate, TMB, and CSC characteristics in the high-risk group were significantly higher than those in the low-risk group. Low-risk patients have active metabolic activity and a more robust immune response. The high- and low-risk groups differed significantly in histology grade, vascular tumor cell type, AFP, new tumor event after initial treatment, main tumor size, cirrhosis, TNM stage, BCLC stage, and CLIP score.Conclusion: The ferroptosis and pyroptosis molecular subtype-related signature identified and validated in this work is applicable for prognosis prediction, immune microenvironment estimation, stem cell characteristics, and clinical feature assessment in HCC.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3128-3128 ◽  
Author(s):  
María José Terol ◽  
Ana Isabel Teruel ◽  
Paula Amat ◽  
Danella Elaluf ◽  
Mar Tormo ◽  
...  

Abstract Abstract 3128 Background: follicular lymphoma is an incurable, long-lasting disease with an heterogeneous outcome. Several prognostic systems have been proposed, and recently a new one, the FLIPI2 score based on five parameters has been published. However, in order to confirm its prognostic utility, further studies at other centers are highly recommendable. Aim: to validate the new FLIPI2 score in independent series of follicular lymphoma patients diagnosed at our institution between February 1990 and July 2010. Patients and methods. We considered 180 patients consecutively diagnosed with follicular diagnosis in the period described and from whom all variables required were available. The variables included were: beta2microglobulin higher than the upper normal value, longest diameter of the largest involved node longer than 6 cm, bone marrow infiltration, hemoglobin level lower than 120 g/L and age older than 60 years (one point if present). Three risk groups were identified: low risk (0 points), intermediate risk (1 -2) and high risk (3 or more) Progression-free survival was measured from date of treatment until date of progression or death from any cause. Continuous variables were summarized as median and range, categorical variables reported as counts, and PFS and OS carried out using the Kaplan-Meier method and curves compared by the log-rank test. Results: median age was 55 years (range, 24 to 77), male sex 92 (51%), Ann Arbor Stage I-II: 32(18%), III-IV: 143 (82%), age > 60 y 70 (39%), Hb < 120 g/L 38 (21%), β2microglobulin > UNV: 45 (25%), LDH > UNV: 34 (19%), bone marrow infiltration 82 (48%), longer diameter of the largest involved node > 6 cm 64 (36%). 47 patients (26%) received rituximab-containing regimens and 124 received conventional chemotherapy regimens (pre-rituximab era). Median follow-up of the series was 66.9 months (range,1.3-221). Using the FLIPI score (n=162) 58 patients (36%) were in the low risk group, 54 (33%) were in the intermediate group and 50 (31%) in the high risk group. Using the FLIPI2 (n=180) 36 patients (20%) were in the low risk group, 103 (57%) in the intermediate group and 41 (23%) in the high risk group. According to FLIPI 5y- PFS rate was 79% for the low risk group, 63% for the intermediate group and 32% for the high risk group, p < 0.001. According to FLIPI2 score, 5y-PFS rate was 82% for the low risk, 54% for the intermediate and 43% for the high risk groups, p=0.017. Concerning OS, applying the FLIPI, 5y-OS rate for the low, intermediate and high risk groups were 94%m 84% and 64%, respectively, p=0.003. Using the FLIPI2, 5y-OS for the low, intermediate and high risk groups were 96%, 80% and 67% respectively, p=0.006. Conclusions: in our experience the FLIPI2 score is a reproducible prognostic index in patients with follicular lymphoma although the FLIPI score seems to discriminate better between groups than the FLIPI2 score. Disclosures: No relevant conflicts of interest to declare.


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