Search

Background Colon cancer with liver metastases (CCLM) characterized by genetic heterogeneity is an evolutionary process leading to variations in response to selective pressure, but the underlying evolutionary models still remains unclear. Methods Total of 30 samples, including primary tumor and two to four matched liver metastases from 8 treatment-naïve patients with CCLM were collected, and subjected to whole-exome DNA sequencing. PyClone was used to calculate intra and inter-tumor heterogeneity, LICHeE was used to reconstruct the cancer phylogeny trees and investigate the subclonal composition. Results The genetic differences were observed between primary and metastatic lesions, as well as among multiple metastases in all patients. The natural history models of colorectal cancer in each case were identified, including parallel, linear, and branching evolution. Liver metastases could originate from primary lesions or other metastases. Pathway and process enrichment analysis also showed obvious heterogeneity and enhancement of several molecular functions. Conclusions Our data reveal the genetic and heterogeneity between primary and metastatic lesions, as well as among multiple metastases and provide genomic evidence for clonal heterogeneity for CCLM.

Emerging evidence suggests that metabolism plays important roles in the initiation and progression of colon cancer (CC) and the outcomes of CC patients. Long non-coding RNAs (lncRNA) are key regulators of regulatory molecules linking to a wide variety of cancer cellular functions. This study aims to develop a metabolic lncRNA signature to help better predict prognosis for CC patients.In the current study, the transcriptome data and clinical data of CC was downloaded from The Cancer Genome Atlas (TCGA). Metabolism-related gene sets were downloaded from the Molecular Signatures Database (MSigDB). Differential lncRNAs related to metabolism was obtained by performing the correlations between differential expression profile of metabolic genes and lncRNAs. To construct a prognostic model of CC based on metabolism-related lncRNAs, we divided patients, whose clinical data were available, into a training set and a validation set at a ratio of 7:3. The prognostic metabolism related-lncRNA signature was established using the training set by univariate and multivariate Cox regression analysis, and the validation set was used to test the capacity of the prognostic model. The correlation between risk score and clinicopathological features, immune function GO and KEGG analysis was investigated using the entire set. Finally, GSEA pathway enrichment analysis was carried out on the entire set samples for the high- and low- risk groups.We identified 604 differential lncRNAs and 252 genes related to metabolism. After univariate and multivariate Cox regression analysis, four lncRNAs were finally identified to build a signature, which was verified the effectiveness by the TCGA validation set. The multivariate Cox regression analysis showed that the risk score, age of diagnosis and T stage were independent prognostic factor for CC patients. It is shown that some immunopathogenesis, GO items and KEGG pathways demonstrated difference between high- and low- risk group.We developed a four-metabolism related-lncRNA signature for prognostic prediction of CC, which may help select high-risk subpopulation patients who require more aggressive therapy or intervention.

IMPORTANCE: Safe and effective prophylactic therapies for radiation-induced dermatitis (RID) remain an unmet need. OBJECTIVE: To determine if epigallocatechin-3-gallate (EGCG) solution reduces the incidence of RID in patients undergoing radiotherapy after breast cancer surgery. DESIGN, SETTING, AND PARTICIPANTS: This phase 2 double-blind, placebo-controlled randomized clinical trial enrolled 180 patients with breast cancer receiving postoperative radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China, between November 2014 and June 2019. Data analysis was performed from September 2019 to January 2020. INTERVENTIONS: Participants were randomly assigned (2:1) to receive either EGCG solution (660 μmol/L) or placebo (0.9% NaCl saline) sprayed to the whole radiation field from day 1 of the radiation until 2 weeks after radiation completion. MAIN OUTCOMES AND MEASURES: The primary end point was incidence of grade 2 or worse RID, defined by the Radiation Therapy Oncology Group scale. The secondary end points included RID index (RIDI), symptom index, changes in the skin temperature measured by infrared thermal images, and safety. RESULTS: A total of 180 eligible patients were enrolled, of whom 165 (EGCG, n = 111; placebo, n = 54) were evaluable for efficacy (median [range] age, 46 [26-67] years). The occurrence of grade 2 or worse RID was significantly lower (50.5%; 95% CI, 41.2%-59.8%) in the EGCG group than in the placebo group (72.2%; 95% CI, 60.3%-84.1%) (P = .008). The mean RIDI in the EGCG group was significantly lower than that in the placebo group. Furthermore, symptom indexes were significantly lower in patients receiving EGCG. Four patients (3.6%) had adverse events related to the EGCG treatment, including grade 1 pricking skin sensation (3 [2.7%]) and pruritus (1 [0.9%]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, prophylactic use of EGCG solution significantly reduced the incidence and severity of RID in patients receiving adjuvant radiotherapy for breast cancer. It has the potential to become a new choice of skin care for patients receiving radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02580279

Objective Several studies have found that epigallocatechin-3-gallate (EGCG) can alleviate acute radiation-induced esophagitis, inhibit pulmonary inflammation and fibrosis, and reduce the severity of cardiovascular disease. Therefore, this study was aimed at exploring the influence of EGCG on late radiation toxicity in the heart, esophagus, and lungs among patients with locally advanced lung cancer. Methods The patients were divided into an EGCG group and a control group, the groups received EGCG and symptomatic treatment, respectively. The Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme was used to determine the late toxicity scores. Tumor responses were evaluated by chest computed tomography (CT), based on the Response Evaluation Criteria in Solid Tumors version 1.1. Results We retrospectively analyzed 74 patients treated at our hospital from September 2012 to September 2016 (37 patients received EGCG and 37 received supportive treatment). The late toxicity scores of the EGCG group decreased compared to those of the control group. An obvious clinical significance was observed for the oral EGCG solution in the treatment and prevention of late cardiac, esophageal, and pulmonary toxicity. However, no significant difference was found (P ​> ​0.05). The tumor response rates were similar in the two groups. Moreover, there was no difference in progression-free survival (PFS) between the groups (P ​> ​0.05). Conclusion Oral EGCG solution might alleviate radiation-induced late cardiac, esophageal, and pulmonary toxicity but has no significant effect on the tumor response rate and PFS following radiotherapy.

Whether chronic exposure to environmental doses of polycyclic aromatic hydrocarbons (PAHs) can lead to neurotoxic effects is still unclear. Hence, the neurotoxic effects of perinatal and juvenile exposure to 16 priority-controlled PAHs were investigated. The mice were treated with 0, 0.5, 18.75, 50, 1875 μg/kg/day of PAHs corresponding to various population exposure concentrations from gestation to postnatal day 60. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hippocampal and cortical neurotransmitter levels were determined using liquid chromatography-tandem mass spectrometry. Typical indicators or outcome of neurotoxicity, including, spatial learning and memory ability, hippocampal long-term potentiation (LTP) and dendritic spine density were evaluated via Morris water maze tests, electrophysiological experiments and Golgi-Cox assays, respectively. The results showed that exposure to different levels of PAH could not increase oxidative DNA damage level. Mice exposed to 0.5, 50 and 1875 μg/kg/day PAHs had significantly longer escape latency than the control group only on the 1st day (p 0.05). The number of platform crossings and the time spent in target quadrant were similar between the control and the PAHs-exposed mice. Compared with the control mice, only those exposed to 50 μg/kg/day PAHs had significantly lower LTP in hippocampal CA1 region and dendritic spine density in hippocampal DG region (p 0.05). Except for serotonin, no significant difference in hippocampal and cortical neurotransmitter concentrations was observed between the control and PAHs-exposed groups. Taken together, perinatal and juvenile exposure to environmental doses of PAHs had no profound effect on spatial learning and memory abilities, hippocampal LTP, dendritic spines density, and neurotransmitter levels. These unexpected findings were quite different from previous in vivo studies which commonly used 2-3 orders of magnitude higher PAHs doses to treat animals. Thus, the environmental dose is a crucial reference for future toxicological research to reveal the actual toxic mechanisms and human health effects of PAHs exposure.

Radiation-induced oral mucositis has a dismal outcome with limited treatment options. We conducted a phase I study to evaluate the safety and preliminary efficacy of epigallocatechin-3-gallate (EGCG) mouthwash when given along with radiation in head and neck cancer. Patients with pathologically confirmed head and neck cancer were eligible for this study. EGCG mouthwash was administered at the assigned dosage level (starting at 440 μmol/L, three times a day) in a standard 3 + 3 dose escalation design. Mucosal toxicity, patient satisfaction, and mucositis-related pain (MTP) were assessed weekly. The primary endpoint was safety of EGCG, and the secondary endpoint was to determine the relief of the mucositis symptom. The pre- and post-treatment parameters were compared using the paired t-test. 20 patients were enrolled. The maximum tolerated dose of the EGCG mouthwash was 2200 μmol/L. Burning (n = 1/20) and nausea (n = 3/20) were the most common toxicities. No patients experienced WHO Grade 3 or higher mucositis. MTP scores significantly decreased after EGCG administration over time (p

To assess the spatial epidemic characteristics of TB and identify the key areas for disease prevention and control.To explore the spatial distribution and socioeconomic influencing factors of TB in mainland China from 2013 to 2016.Spatial autocorrelation was used to explore the spatial distribution characteristics of TB at the quantitative level. Ordinary least squares (OLS) and geographically weighted regression (GWR) models were conducted to explore the association between factors and TB incidence from both global and local perspectives.There was a significant positive spatial autocorrelation of TB at the provincial level (P 0.05): hot spots were mainly located in the west of Xinjiang and Tibet, and cold spots in the eastern coastal areas. Four latent factors on the socioeconomic dimension, involving the proportion of illiterate people aged 15 and over, per capita disposable income in rural areas, the number of health technicians per 1000 population and the urban population density, were associated with TB incidence. The GWR model showed that the effect of the same factor on TB incidence varied with geographical location.Spatial clustering of TB incidence in mainland China still exists. The differences of socioeconomic factors in different locations can be confirmed by GWR model. Targeted preventive and control measures or policies will be conducive in effectively reducing the incidence of TB, especially in hot spots.Evaluer les caractéristiques spatiales épidémiques de la tuberculose (TB) et identifier les domaines clés pour la prévention et le contrôle de la maladie.Explorer la distribution spatiale et les facteurs d'influence socioéconomiques de la TB en Chine continentale de 2013 à 2016. MÉTHODES: Une autocorrélation spatiale a été utilisée pour explorer les caractéristiques de distribution spatiale de la TB à une échelle quantitative. Les moindres carrés ordinaires (OLS) et des modèles de régression géographiquement pondérés (GWR) ont été utilisés pour explorer l'association entre les facteurs et l'incidence de la TB, tant du point de vue global que local. RÉSULTATS: Il y avait une autocorrélation spatiale positive significative au niveau provincial (P0,05): les points chauds étaient principalement situés à l'ouest du Xinjiang et du Tibet et les points froids dans les zones côtières est. Quatre facteurs latents de dimension socioéconomique, à savoir la proportion d'analphabètes âgés de 15 ans et plus, le revenu disponible par habitant en zone rurale, le nombre de techniciens de la santé pour 1000 habitants et la densité de la population urbaine ont été associés à l'incidence de la TB. Le modèle GWR a montré que l'effet du même facteur sur l'incidence de la TB variait avec la localisation géographique.Le regroupement spatial de l'incidence de la TB en Chine continentale existe toujours. Les différences de facteurs socioéconomiques dans différents endroits peuvent être confirmées par le modèle GWR. Des mesures ou politiques de prévention et de contrôle ciblées permettront de réduire efficacement l'incidence de la TB, en particulier dans les zones les plus touchées.

Understanding etiological role and epidemiological profile is needed to improve clinical management and prevention of acute respiratory infections (ARIs). A 5-year prospective study about active surveillance for outpatients and inpatients with ARIs was conducted in Gansu province, China, from January 2011 to November 2015. Respiratory specimens were collected from patients and tested for eight respiratory viruses using polymerase chain reaction (PCR) or reverse transcription polymerase chain reaction (RT-PCR). In this study, 2768 eligible patients with median age of 43 years were enrolled including pneumonia (1368, 49.2%), bronchitis (435, 15.7%), upper respiratory tract infection or URTI (250, 9.0%), and unclassified ARI (715, 25.8%). Overall, 29.2% (808/2768) were positive for any one of eight viruses, of whom 130 cases were identified with two or more viruses. Human rhinovirus (HRV) showed the highest detection rate (8.6%), followed by influenza virus (Flu, 7.3%), respiratory syncytial virus (RSV, 6.1%), human coronavirus (hCoV, 4.3%), human parainfluenza (PIV, 4.0%), adenovirus (ADV, 2.1%), human metapneumovirus (hMPV, 1.6%), and human bocavirus (hBoV, 0.7%). Compared with URTI, RSV was more likely identified in pneumonia (χ2 = 12.720, P

Background: Recent studies confirmed that immunotherapy showed prominent efficacy in non-small cell lung cancer (NSCLC). Cancer stem cells/cancer initiating cells are resistant to anticancer treatment. The purpose of the study was to analyze the correlation of cancer stem cells/cancer initiating cells and tumor-infiltrating immune cells in NSCLC. Methods: CD133, octamer 4 (OCT-4), CD8, CD56, human leukocyte antigen (HLA) class I and programmed death ligand-1 (PD-L1) were assessed in 172 resected NSCLC samples. The staining was analyzed and scored by the pathologist who was blinded to the clinical pathological data of the patients. Results: High CD8+ T cell infiltration was correlated significantly with squamous cell carcinoma histology (p=0.008). High PD-L1 expression (≥10%) was associated with high tumor status (p=0.043). Pearson's correlation test showed that CD56+ cells were negatively correlated with CD133 expression (r=-0.361, p

// Xinzhe Dong 1, 2 , Xiaorong Sun 3 , Xianguang Zhao 1 , Wanqi Zhu 1 , Lu Sun 4 , Yong Huang 3 , Wenwu Li 3 , Honglin Wan 5 , Ligang Xing 1, 2 , Jinming Yu 1, 2 1 Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, Shandong, China 2 Key Laboratory of Radiation Oncology of Shandong Province, Shandong Academy of Medical Sciences, Jinan, Shandong, China 3 Department of Radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China 4 Jinan University, Jinan, Shandong, China 5 College of Physics and Electronic Science, Shandong Normal University, Jinan, Shandong, China Correspondence to: Ligang Xing, email: sdcancerhospital@163.com Keywords: positron emission tomography, FDG, esophageal carcinoma, intratumoral heterogeneity, prognosis Received: July 18, 2016 Accepted: January 10, 2017 Published: January 19, 2017 ABSTRACT Objective: To evaluate the impact of intratumoral metabolic heterogeneity measured by 18F-FDG PET imaging on postoperative recurrence and survival for patients with esophageal squamous cell carcinoma (ESCC). Results: AUC-CSH, metabolic tumor volume and pN-stage were significant prognostic factors for RFS. Additionally, tumor recurrence of the low AUC-CSH group (≤ 0.478) was 3 times higher than high group ( P = 0.015). The median OS of patients with advanced AJCC stage or low AUC-CSH was also significantly shorter than that of patients with stage I & II or high AUC-CSH ( P = 0.021, 0.009). Multivariate analysis identified the AUC-CSH to be the only significant risk factor for postoperative recurrence and overall survival in whole-group and stage III patients. Materials and Methods: 116 ESCC patients who underwent staging 18F-FDG PET-CT scan and surgical resection were reviewed. The metabolic parameters were assessed as follows: maximum standardized uptake value (SUV max ), metabolic tumor volume, and the area under the curve of the cumulative SUV-volume histogram (AUC-CSH), which is known to reflect the intratumoral metabolic heterogeneity. Regression analyses were used to identify clinicopathological and imaging variables associated with relapse-free survival (RFS) and overall survival (OS). Conclusions: Intratumoral metabolic heterogeneity characterized by AUC-CSH can predict postoperative recurrence and survival in patients with resectable ESCC.

There are few effective treatment options for radiation-induced dermatitis in breast cancer patients. We conducted a single-arm trial to tested the hypothesis that topical epigallocatechin-3-gallate (EGCG) is effective against radiation-induced dermatitis in breast cancer patients undergoing radiotherapy. Forty-nine patients participated in this study. The patients underwent mastectomy followed by adjuvant radiotherapy. Topical EGCG was applied daily, starting when grade I dermatitis appeared and ending two weeks after radiotherapy. The maximum dermatitis observed during the EGCG treatment was as follows: Grade 1 toxicity, 71.4% (35 patients); grade 2 toxicity, 28.6% (14 patients); there were no patients with grade 3 or 4 toxicity. The majority of the radiation-induced dermatitis was observed 1 week after the end of radiotherapy. EGCG reduced the pain in 85.7% of patients, burning-feeling in 89.8%, itching in 87.8%, pulling in 71.4%, and tenderness in 79.6%. These findings suggest topical EGCG may be an effective treatment for radiation-induced dermatitis and has acceptable toxicity.

The ability of acidic (AcW) and alkaline electrolyzed waters (AlW) to improve the flavour of persimmon (Diospyros kaki L.) wine was evaluated. Wines made with AcW (WAcW) were significantly better than wines made with AlW or pure water (PW) in aroma, taste, and colour. Volatile analysis showed that WAcW has high alcohol and ester contents, including 2-phenylethanol, isopentanol, isobutanol, ethyl dodecanoate, phenethyl acetate, and butanedioic acid diethyl ester. The total amino acid content of persimmon slurry soaked with AcW reached 531.2 mg/l, which was much higher than those of the slurries soaked in AlW (381.3 mg/l) and PW (182.7 mg/l). The composition of major amino acids in the AcW-soaked slurry may contribute to the strong ester flavour of WAcW. This is the first report to suggest that electrolyzed functional water (EFW) can be used to improve wine flavour, leading to the possible use of EFW in food processing.

Purpose To investigate whether the apparent diffusion coefficient (ADC) values acquired from diffusion-weighted magnetic resonance imaging (DW-MRI) are correlated with molecular markers Ki-67, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) in rectal cancer (RC). Materials and Methods Ninety-one patients (64 males and 27 females) diagnosed with rectal cancer underwent 3.0T DW-MRI before any anticancer treatment. DW-MRI was performed using the single-shot echo-planar imaging technique (b = 0 and b = 800 s/mm2). The patients underwent surgery within 1 week after MRI. Ki-67, HIF-1α, and VEGF expression were assessed by immunohistochemistry at both the resected margins and the center of the tumor. Results We noted that ADC values correlated positively with histology differentiations (r = 0.336, P = 0.001) and negatively with carcinoembryonic antigen level (r = −0.217, P = 0.039) in RC. Both the value and the level of Ki-67 expression were correlated inversely with the ADC values (r = −0.475, P

Background and purpose This trial investigated whether epigallocatechin-3-gallate (EGCG), a radioprotector, could be effective in the prevention and treatment of acute radiation-induced esophagitis (ARIE). Methods and materials This is a phase II study of EGCG combined with chemoradiation in unresectable stage III non-small-cell lung cancer or limited stage small cell lung cancer. Patients were randomized into a prophylactic EGCG group (arm A), a therapeutic EGCG group after the occurrence of esophagitis (arm B) or conventional therapy group (arm C). Esophagitis grades, pain and dysphagia scores were recorded weekly. Adjusted esophagitis index (AEI), pain index (API) and dysphagia index (ADI) were calculated to reflect changes in esophagitis grade, pain score and dysphagia score throughout treatment. Results A total of 83 patients were eligible for toxicity analysis (arm A vs arm B vs arm C: N = 28:27:28). There was no significant difference in the baseline characteristics among three arms of the patients. The difference in the maximum esophagitis grade among three groups was statistically significant (P = 0.004). The maximum ARIE for patients with EGCG was significantly lower than for those with conventional therapy. The mean AEI of arm A was lower than that of arm B, while the mean AEI of arm C was the highest (arm A vs arm B, P = 0.028; arm B vs arm C, P = 0.002). Furthermore, API and ADI were significantly lower in patients receiving EGCG than in conventionally treated patients. Conclusion The application of EGCG could effectively alleviate acute radiation esophagitis in advanced lung cancer without obvious side effects. Prophylactic application of EGCG had a slight advantage over therapeutic use in treatment of acute esophagitis.

To investigate whether the apparent diffusion coefficient (ADC) values acquired from diffusion-weighted magnetic resonance imaging (DW-MRI) are correlated with molecular markers Ki-67, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) in rectal cancer (RC).Ninety-one patients (64 males and 27 females) diagnosed with rectal cancer underwent 3.0T DW-MRI before any anticancer treatment. DW-MRI was performed using the single-shot echo-planar imaging technique (b = 0 and b = 800 s/mm(2) ). The patients underwent surgery within 1 week after MRI. Ki-67, HIF-1α, and VEGF expression were assessed by immunohistochemistry at both the resected margins and the center of the tumor.We noted that ADC values correlated positively with histology differentiations (r = 0.336, P = 0.001) and negatively with carcinoembryonic antigen level (r = -0.217, P = 0.039) in RC. Both the value and the level of Ki-67 expression were correlated inversely with the ADC values (r = -0.475, P 0.001 and r = -0.555, P 0.001). There was a weak negative correlation between HIF-1α expression and the ADC values (r = -0.304, P = 0.003). VEGF expression was correlated inversely with the ADC values of the RCs (r = -0.290, P = 0.005). However, no significant correlation was observed between VEGF expression and the ADC values in pT4 RCs (r = -0.166, P = 0.255).Our results suggest that the ADC values on DW-MRI may be used as a measurement of cell proliferation and hypoxia in RC. J. Magn. Reson. Imaging 2016;44:594-600.

The addition of trastuzumab to chemotherapy was demonstrated to be beneficial for advanced human epidermal growth factor receptor-2 (HER-2) positive gastric cancer. However, the HER-2 status of rectal cancer remains uncertain. This study aimed to determine the HER-2 expression in a large multicenter cohort of rectal cancer patients. The clinical and pathological features of 717 patients were retrospectively reviewed. All the patients were diagnosed with primary rectal adenocarcinoma without distant metastasis and took surgery directly without any preoperative anticancer treatment. HER-2 status was assessed on resected samples. A total of 99 cases with IHC3+ and 16 cases with IHC 2+ plus gene amplification were determined as HER-2 positive. 22.6% of HER-2 positive patients had local recurrence, whereas 16.9% of HER-2 negative patients did (P = 0.146). HER-2 positive tumors were more likely to have distant metastasis (P = 0.007). Univariate analysis revealed that pathological tumor stage, pathological node stage, positive margin, and lymphovascular invasion were significantly correlated with 5-year disease-free survival (DFS) and 5-year overall survival (OS). The patients with >10 dissected lymph nodes showed significantly longer OS (P = 0.045) but not DFS (P = 0.054). HER-2 negative patients had significantly better 5-year DFS (P < 0.001) and 5-year OS (P = 0.013) than those of the HER-2 positive patients. In the subgroup analysis for the early rectal cancer and locally advanced rectal cancer, HER-2 was also a poor predictor for survival. Multivariate analysis revealed that HER-2 was an independent prognostic factor for 5-year DFS (hazard ratio [HR] = 1.919, 95% confidence interval [CI] 1.415–2.605, P < 0.001) and for 5-year OS (HR = 1.549, 95% CI 1.097–2.186, P = 0.013). When the treatment was included in the analysis for locally advanced patients, HER-2 was a prognostic factor for 5-year DFS (P = 0.001) but not for 5-year OS (P = 0.106). This study confirmed that HER-2 was expressed in a part of patients with rectal cancers and might be used as a negative predictor. The results may support the trials to assess the efficacy of trastuzumab in treating HER-2 positive rectal cancer patients.

Background Genes that regulate stem cell function are suspected to exert adverse effects on prognosis in malignancy. However, diverse cancer stem cell signatures are difficult for physicians to interpret and apply clinically. To connect the transcriptome and stem cell biology, with potential clinical applications, we propose a novel computational “gene-to-function, snapshot-to-dynamics, and biology-to-clinic” framework to uncover core functional gene-sets signatures. This framework incorporates three function-centric gene-set analysis strategies: a meta-analysis of both microarray and RNA-seq data, novel dynamic network mechanism (DNM) identification, and a personalized prognostic indicator analysis. This work uses complex disease acute myeloid leukemia (AML) as a research platform. Results We introduced an adjustable “soft threshold” to a functional gene-set algorithm and found that two different analysis methods identified distinct gene-set signatures from the same samples. We identified a 30-gene cluster that characterizes leukemic stem cell (LSC)-depleted cells and a 25-gene cluster that characterizes LSC-enriched cells in parallel; both mark favorable-prognosis in AML. Genes within each signature significantly share common biological processes and/or molecular functions (empirical p = 6e-5 and 0.03 respectively). The 25-gene signature reflects the abnormal development of stem cells in AML, such as AURKA over-expression. We subsequently determined that the clinical relevance of both signatures is independent of known clinical risk classifications in 214 patients with cytogenetically normal AML. We successfully validated the prognosis of both signatures in two independent cohorts of 91 and 242 patients respectively (log-rank p