Low serum vitamin D concentrations are associated with obese but not lean NAFLD: a cross-sectional study.

BACKGROUND: A low serum vitamin D concentration has been reported to be associated with an increased risk of non-alcoholic fatty liver disease (NAFLD); however, whether lean or obese individuals show a similar association between vitamin D and NAFLD remains speculative. This study aimed to explore the relationship between serum vitamin D concentration and NAFLD in lean and obese Chinese adults. METHODS: This cross-sectional study included 2538 participants (1360 men and 1178 women) who underwent health checkups at the First Affiliated Hospital, Zhejiang University School of Medicine in 2019. NAFLD was diagnosed by liver ultrasound excluding other causes. The association of serum vitamin D concentration with NAFLD was analyzed in lean and obese participants. RESULTS: The overall prevalence of NAFLD was 33.61% (13.10% in lean and 53.32% in obese) in this study population. The serum vitamin D levels of obese NAFLD patients were lower than those of obese NAFLD-free controls. However, the serum vitamin D levels of lean NAFLD patients were comparable to those of lean NAFLD-free controls. Serum vitamin D level was negatively correlated with the prevalence of NAFLD in obese but not lean participants. Serum vitamin D level was independently associated with the risk of NAFLD in obese participants, with an adjusted odds ratio (95% CI) of 0.987 (0.981-0.993). However, serum vitamin D level was not related to the risk of NAFLD in lean participants. CONCLUSIONS: A low serum vitamin D level is associated with NAFLD in obese but not lean participants.

Association between Serum Free Fatty Acids to HDL-Cholesterol Ratio and Nonalcoholic Fatty Liver Disease: a Cross-Sectional Study.

BACKGROUND: This cross-sectional study aimed to investigate the association between serum free fatty acids and high-density lipoprotein-cholesterol ratio (FHR) and nonalcoholic fatty liver disease (NAFLD) in a Chinese population. METHODS: A total of 760 NAFLD subjects and 379 healthy controls who took their annual health checkups were enrolled during 2019. Fasting blood samples were obtained from the population. NAFLD was diagnosed based on hepatic ultrasound examination. RESULTS: Serum FHR (*100) in NAFLD subjects was significantly higher than that in controls. We found that the serum FHR in NAFLD participants was positively correlated with BMI, DBP, WBC, HGB, ALT, AST, GGT, TG, FPG, UA, and hsCRP. Univariate and multivariate logistic regression analysis showed that FHR was independently associated with the presence of NAFLD. The area under curve (AUC) of the receiver operating characteristic (ROC) curve of FHR for NAFLD was 0.781 with the 95% confidence interval from 0.753 to 0.810. The optimal cutoff point of FHR for predicting NAFLD was 41.14 with 78.8% sensitivity and 77.3%, respectively. CONCLUSIONS: FHR was significantly associated with NAFLD and may serve as an effective indicator in NAFLD patients.

Association between Monocyte to High-Density Lipoprotein Cholesterol Ratio and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

BACKGROUND: The aim of the present study was to investigate the association between monocyte to high-density lipoprotein cholesterol ratio (MHR) and nonalcoholic fatty liver disease (NAFLD) in Chinese population. METHODS: We enrolled 14189 individuals who attended their annual health examinations in the study. We performed the anthropometric and laboratory measurements and diagnosed NAFLD by hepatic ultrasonography without evidence of other etiologies of chronic liver disease. Student's t-test, Mann-Whitney U test, and chi-squared (χ 2) test was used to compare the differences of clinical characteristics between participants with or without NAFLD. Pearson's and Spearman's analyses were performed to assess the correlation of MHR and NAFLD risk factors. Univariate and multivariate logistic regression analyses were conducted to explore whether MHR associated with NAFLD. RESULTS: Thirty-five percent of the participants enrolled were diagnosed with NAFLD. Compared with healthy controls, NAFLD patients were male predominant, older, and had higher body mass index, waist circumference, and systolic and diastolic blood pressure, as well as higher levels of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, triglyceride, total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, glycated hemoglobin A1c, and serum uric acid, but lower levels of serum high-density lipoprotein cholesterol. Besides, MHR was significantly higher in NAFLD patients than healthy controls [5.35 (4.18-6.84) versus 4.53 (3.48-5.93), P < 0.001]. MHR quartiles were positively related to the prevalence of NAFLD (P < 0.001 for trend). In multivariate logistic regression analysis, MHR was positively associated with the risk of NAFLD after adjusting age, gender, body mass index, waist circumference, diastolic blood pressure, alanine aminotransferase, triglyceride, total cholesterol, fasting plasma glucose, and serum uric acid (OR: 1.026, 95% CI: 1.002-1.052; P = 0.037). CONCLUSIONS: MHR is significantly and positively associated with the risk of NAFLD.

Serum Thyroid Hormones Levels are Significantly Associated with Nonalcoholic Fatty Liver Disease in Euthyroid Chinese Population.

BACKGROUND: Thyroid hormones play an essential role in metabolic homeostasis. Previous studies have demon-strated a close relationship between thyroid abnormalities and metabolic disorders. This retrospective cross-sectional study was to investigate whether significant differences of circulating thyroid profiles exist and to explore the potential of serum thyroid hormones in reflecting advanced fibrosis in subjects with Nonalcoholic Fatty Liver Disease (NAFLD). METHODS: Abdominal ultrasonography was performed to diagnose NAFLD. For all the participants including 522 NAFLD patients and 415 gender- and age-matched controls recruited, demographic, clinical data and thyroid functions were recorded. Fasting serum thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4), total thyroxine (TT4), total triiodothyronine (TT3), and thyroid-stimulating hormone (TSH) were evaluated. RESULTS: Serum FT3 levels in subjects with NAFLD were significantly reduced, while TSH was increased compared to that in controls. The NAFLD subjects with metabolic syndrome (MS) had significantly lower FT3 and FT4 levels and higher TSH levels than the non-MS group. Serum TSH levels were positively associated with the risk for NAFLD, while FT3 levels were inversely correlated with NAFLD. Among thyroid hormones, low serum FT4 was the only independent predictor of reflecting advanced fibrosis in NAFLD participants. CONCLUSIONS: An altered thyroid profile not only can be significantly associated with an increased incidence of NAFLD, but also had clinical predictive value for assessing significant fibrosis.

Association between Serum Ferritin Level and Nonalcoholic Fatty Liver Disease in a Non-Obese Chinese Population: a Cross-Sectional Study.

BACKGROUND: The aim of the study is to evaluate the cross-sectional association between serum ferritin level and nonalcoholic fatty liver disease (NAFLD) in a non-obese Chinese population. METHODS: A cross-sectional study was performed among 1,020 non-obese subjects (body mass index < 25 kg/m2) who took their annual health examination at the First Affiliated Hospital, College of Medicine, Zhejiang University. Serum ferritin level and other clinical and laboratory parameters were measured in the population. Liver ultrasound examinations were performed to diagnose NAFLD. RESULTS: Of the 1,020 enrolled participants, 148 (14.51%) fulfilled the diagnostic criteria for NAFLD. Subjects with NAFLD had a higher level of serum ferritin than individuals without NAFLD in non-obese subjects. Serum ferritin level was significantly and positively correlated with parameters of MS (BMI, SBP, TG and FPG) in NAFLD group. Stepwise logistic regression analysis showed that serum ferritin level was significantly associated with the risk factor for NAFLD. After adjusting for confounders, serum ferritin level was an independent factor predicting advanced fibrosis (FIB-4 ≥ 1.3) in NAFLD participants. CONCLUSIONS: Increased serum ferritin level is significantly associated with NAFLD, and elevated serum ferritin level is an independent factor predicting advanced fibrosis for NAFLD in a non-obese Chinese population.

MiR-218-XOR-ROS Pathway Regulates the Progression of Nonalcoholic Steatohepatitis.

BACKGROUND: To investigate the role of the miR-218-xanthine oxidoreductase (XOR) pathway in the pathogenesis of nonalcoholic steatohepatitis (NASH) and to explore the potential downstream mechanisms involving oxidative stress and energy metabolism. METHODS: The NASH animal model was established by feeding BALB/c mice with an MCD diet, while BRL-3A cells were cultured with a mixture of oleate and palmitate for 72 hours to mimic the steatosis and inflammation of NASH in vitro. The steatosis and inflammation levels were assessed by H-E/oil-red staining and serum/supernatant TG, ALT, and AST levels. The apoptosis degree was tested by the TUNEL/flow cytometry method both in animals and cultured cells. The XOR and miR-218 levels were detected by western blotting and qRT-PCR. RESULTS: Decreased miR-218 and increased XOR levels were identified in the NASH animal and cell models, while the regulation of miR-218 on XOR was also confirmed. NASH alleviation was achieved after miR-218 over-expression in vivo and in vitro, according to the declination of steatosis and inflammation-related markers. Although H2O2 and ATP levels were increased and decreased in NASH models, respectively, antagonizing miR-218 could significantly alleviate those changes. CONCLUSIONS: The miR-218-XOR pathway may provide a novel mechanism and treatment option for NASH.

Association Between Urinary Alpha1-Microglobulin Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

BACKGROUND: We aimed to explore the association between urinary alpha1-microglobulin (A1M) levels and nonalcoholic fatty liver disease (NAFLD) in a Chinese population. STUDY: We performed a cross-sectional study among 2,215 Chinese who attended their annual health examination at First Affiliated Hospital, College of Medicine, Zhejiang University. Urinary A1M-creatinine ratio and other clinical and laboratory parameters were measured. RESULTS: A total of 20.9% of subjects fulfilled the diagnostic criteria of NAFLD. NAFLD subjects had significantly higher urinary A1M-creatinine ratios. These levels were positively associated with NAFLD prevalence. The association between A1M-creatinine ratio and NAFLD was independent of hyperglycemia status. Stepwise regression showed that urinary A1M-creatinine ratio was significantly associated with the risk for NAFLD. Urinary A1M-creatinine ratio was an independent factor predicting advanced fibrosis (FIB-4 ≥1.3) in NAFLD patients. CONCLUSIONS: Our results showed a significant association between urinary A1M-creatinine ratio and NAFLD.

Association between urine retinol-binding protein levels and nonalcoholic fatty liver disease: A cross-sectional study in Chinese population.

OBJECTIVE: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increased, becoming a public health problem worldwide. Our objective was to investigate the association between urine retinol-binding protein (RBP) and NAFLD in a Chinese population and develop a multivariate logistic regression model for NAFLD prediction. METHODS: A total of 317 NAFLD patients and 391 healthy controls were enrolled in this cross-sectional study based on inclusion and exclusion criteria, from whom fasting urine and blood were collected for further study. Urine RBP level and other parameters were measured and compared between NAFLD subjects and controls. RESULTS: Urine RBP levels (expressed by RBP/creatinine ratio) in NAFLD patients were significantly higher than controls (median 133.1 mg/g vs 110.7 mg/g; P < .001). Urine RBP/creatinine ratio was verified as an independent factor for NAFLD prediction after adjustment in multivariate logistic regression. The area under curve (AUC) of receiver operating characteristic (ROC) was 0.889 with the 95% confidence interval from 0.867 to 0.912.With a cutoff point of 0.215, the sensitivity and specificity of urine RBP/creatinine ratio in NAFLD prediction were 81.1% and 84.5%, respectively. CONCLUSION: Our results demonstrated that urine RBP/creatinine ratio was an independent risk factor for NAFLD while the predictive model for NAFLD diagnosis is noninvasive with high sensitivity and specificity.

Association Between Serum Free Fatty Acids Levels and Gestational Diabetes Mellitus: a Cross-Sectional Study.

BACKGROUND: This study aimed to assess the relationship between serum free fatty acid (FFA) levels and gestational diabetes mellitus (GDM) in Chinese pregnant women. METHODS: A cross-sectional study was performed among 779 eligible pregnant women who underwent detailed prenatal visits in Hangzhou, China. RESULTS: Patients with GDM had significantly higher serum FFA levels than those without GDM. Spearman's correlation analysis showed that FFA levels were positively correlated with fasting plasma glucose, 1hPG, 2hPG, HOMA-IR, triglyceride, and sialic acid (p < 0.05) and negatively correlated with serum amylase level (all with p < 0.05). Stepwise logistic regression analysis further showed that elevated FFA levels significantly contributed to the risk for GDM. CONCLUSIONS: Our findings suggested that serum FFA levels were significantly associated with GDM.

Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study.

BACKGROUND: Metabolic syndrome is closely associated with an increased risk for fatty liver disease morbidity and mortality. Recently, studies have reported that participants with fatty liver disease have higher serum alpha-fetoprotein levels than those without. We investigated the association between alpha-fetoprotein levels and the prevalence of metabolic syndrome in a Chinese asymptomatic population. METHODS: A cross-sectional study was performed with 7,755 participants who underwent individual health examinations. Clinical and anthropometric parameters were collected and serum alpha-fetoprotein levels and other clinical and laboratory parameters were measured. Logistic regression analysis was used to examine associations between alpha-fetoprotein and metabolic syndrome. RESULTS: Participants with metabolic syndrome had significantly higher (p < 0.001) alpha-fetoprotein levels than those without, though all alpha-fetoprotein levels were within the reference interval. The association between the components of metabolic syndrome (central obesity, elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose) and alpha-fetoprotein levels was evaluated. Alpha-fetoprotein levels in the elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose groups were significantly different (p=0.002, p < 0.001, p=0.020) compared with alpha-fetoprotein in the normal triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose groups. Logistic regression analyses showed an association between alpha-fetoprotein levels and increased risk for metabolic syndrome, the presence of reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose, but not with obesity, elevated blood pressure, or triglycerides. CONCLUSIONS: These results suggest a significant association between alpha-fetoprotein and metabolic syndrome.

Low Serum Amylase is Associated with Gestational Diabetes Mellitus in Chinese Pregnant Women.

BACKGROUND: The association between low serum amylase levels and type 2 diabetes mellitus and metabolic syndrome has been clearly disclosed. However, the relationship between serum amylase levels and gestational diabetes mellitus (GDM) has not been extensively studied. This study aimed to assess the association of serum amylase with GDM. METHODS: A cross-sectional study was performed among 878 Chinese pregnant women who underwent detailed prenatal visits in Hangzhou, China. RESULTS: A total of 108 (12.30%) subjects fulfilled the diagnostic criteria of GDM. Patients with GDM had significantly lower levels of serum amylase than those without GDM. The prevalence rate of GDM decreased across serum amylase increasing tertiles (p for trend < 0.001). Correlation analysis showed that serum amylase level was negatively correlated with fasting plasma glucose, 1hPG, 2hPG, HOMA-IR, triglyceride, free fatty acid, and thyroid stimulating hormone (all with p < 0.05). Multiple logistic regression showed that low serum amylase level predicted increased risk of GDM. CONCLUSIONS: Our findings suggest that low serum amylase level is significantly associated with increased risk of GDM.

Association between Serum Sialic Acid Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

BACKGROUND: To assess the association between serum sialic acid (SA) levels and nonalcoholic fatty liver disease (NAFLD) in a Chinese population. METHODS: A cross-sectional study was performed among 3,898 Chinese who took their annual health examination. Serum SA levels and other clinical and laboratory parameters were measured. RESULTS: A total of 18.11% fulfilled the diagnostic criteria of NAFLD. NAFLD subjects with/without metabolic syndrome (MS) had significantly higher serum SA levels than those without NAFLD. Serum SA levels were significantly and positively correlated with components of MS (body mass index, systolic blood pressure, diastolic blood pressure, triglyceride and fasting plasma glucose) in the NAFLD group. Stepwise logistic regression analysis showed that SA levels were significantly associated with the risk factor for NAFLD. Serum SA levels were negatively correlated with the FIB-4 score, and lower serum SA levels were independent factors predicting advanced fibrosis in subjects with NAFLD. CONCLUSIONS: Our results showed a significant association between serum SA levels and NAFLD.

Laboratory findings in patients with avian-origin influenza A (H7N9) virus infections.

Reports describing the laboratory findings associated with human H7N9 infections are limited. In this study, the laboratory findings of 39 patients with confirmed H7N9 infection were analyzed retrospectively. Patients were enrolled following admission to The First Affiliated Hospital, College of Medicine, Zhejiang University, the primary hospital for the treatment of patients with H7N9 infections in Zhejiang province in China between March and April in 2013. Hematological abnormalities included leukopenia, lymphopenia, thrombocytopenia with prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) as well as elevation of D-dimer levels. Biochemical abnormalities included elevated serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK), alanine aminotransferase (ALT) activities, and increased C-reactive protein (CRP) concentration, as well as hyponatremia, hypokalemia, hypocalcemia, hypoproteinemia, and hypoalbuminemia. Arterial blood gas analysis revealed reduced arterial oxygen (PaO2) and carbon dioxide pressures (PaCO2). The data obtained in this study indicate that such abnormal laboratory features exhibited during the early stage of infection are common but not pathognomonic for the novel avian-origin influenza A strain H7N9; therefore, these features do not to allow the definitive differentiation of H7N9 infection from those of other viruses.

The significance of serum xanthine oxidoreductase in patients with nonalcoholic fatty liver disease.

BACKGROUND: Serum uric acid levels are significantly associated with nonalcoholic fatty liver disease (NAFLD). Xanthine oxidoreductase (XOR) is the key enzyme that catalyzes the formation of uric acid. The aim of this study was to investigate the association between serum XOR activity and NAFLD. METHODS: In this cross-sectional study, serum XOR activity was measured by enzyme-linked immunosorbent assay in 129 patients with NAFLD and 71 controls. RESULTS: Serum XOR activity was markedly higher in patients with NAFLD than in the controls (p < 0.001). Serum XOR activity positively correlated with markers of liver injury and indices of oxidative stress. Moreover, patients with high XOR activity had a higher prevalence of metabolic syndrome. CONCLUSIONS: These data show that serum XOR activity is significantly associated with NAFLD.

Metabolic syndrome and diabetes are associated with low serum amylase in a Chinese asymptomatic population.

OBJECTIVE: Previous studies have shown that lower serum amylase levels are associated with chronic pancreatitis. However, recently, lower serum amylase levels have been associated with metabolic syndrome (MS) and diabetes. The objective of the present study was to investigate the relationship between metabolic syndrome and diabetes and serum amylase levels in Chinese asymptomatic individuals living in Hangzhou, China. METHODS: Serum amylase, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), γ-glutamyltransferase (γ-GT), high sensitivity C reactive protein (hsCRP) and fasting plasma glucose (FPG) levels were measured in 3,728 patients from Hangzhou in China. Study participants were divided into four groups, Q1-Q4, according to serum amylase levels. Odds ratios (OR) of Q1-Q4 were calculated using multivariate logistic regression. RESULTS: Significant differences were found in sex, age, body mass index (BMI), systolic blood pressure, diastolic blood pressure, γ-GT, TG, HDL-C and FPG levels, as well as the prevalence of metabolic syndrome and diabetes among these four groups. Across Q1 to Q4, the prevalence of metabolic syndrome and diabetes decreased from 28.5-15.2% and 10.1-3.6%, respectively. Multiple logistic regression models following adjustment for age, gender, BMI, and γ-GT showed that the prevalence of metabolic syndrome (OR: 1.284; 95% CI: 0.909-1.813) and diabetes (OR: 2.081; 95% CI: 1.230-3.523) in the Q1 was significantly higher compared to the Q4. CONCLUSIONS: Low serum amylase levels are significantly associated with an increased prevalence of metabolic syndrome and diabetes in a Chinese asymptomatic population.

Serum amylase levels are decreased in Chinese non-alcoholic fatty liver disease patients.

BACKGROUND: Low serum amylase levels have been reported in patients with metabolic syndrome (MS), diabetes, and asymptomatic non-alcoholic fatty liver disease (NAFLD). However, no study has yet indicated the serum amylase levels in NAFLD with MS. The aim of the present study was to evaluate serum amylase levels in NAFLD patients with and without MS, and to explore a possible association between serum amylase levels with the components of MS and the degree of hepatic fibrosis in NAFLD patients. METHODS: Our study included 713 NAFLD participants (180 females and 533 males) and 304 healthy control participants (110 females and 194 males). The diagnosis of NAFLD was based on ultrasonography, and advanced fibrosis was assessed by the FIB-4 index. RESULTS: Serum amylase levels were significantly lower in NAFLD patients with MS compared with NAFLD patients without MS and healthy controls (42, 45, and 53 IU/L, respectively). The serum amylase levels of patients with elevated glucose, elevated triglycerides, and low high density lipoprotein cholesterol patients were significantly lower than in case of normal parameters (both p < 0.05). Multivariate logistic regression analysis showed that a relative serum amylase level increase was an independent factor predicting advanced fibrosis (FIB-4 ≥1.3) in NAFLD participants (OR: 1.840, 95% CI: 1.117-3.030, p=0.017). CONCLUSIONS: Compared with NAFLD patients without MS and healthy controls, serum amylase levels were significantly lower in NAFLD patients with MS. Moreover, a relative serum amylase increase may be an independent factor of more advanced hepatic fibrosis.

Association Between Serum Afamin Levels with Nonalcoholic Associated Fatty Liver Disease.

Afamin is a member of the hepatokine that are strongly associated with various metabolic diseases. The relationship between afamin and nonalcoholic fatty liver disease (NAFLD) remains unclear. This study aimed to explore the correlation between serum afamin levels and NAFLD. We analyzed 88 NAFLD patients and 88 age- and sex-matched healthy controls who took their health examinations at the First Affiliated Hospital, Zhejiang University School of Medicine. The association was further confirmed in 22 biopsy-confirmed NAFLD patients and 36 healthy controls. Serum afamin levels were evaluated using an enzyme-linked immunosorbent assay (ELISA). NAFLD patients had significantly higher serum afamin levels than the healthy controls (14.79 ± 5.04 mg/L versus 10.83 ± 3.24 mg/L; P < 0.001). Serum afamin levels were positively correlated with metabolic parameters including the body mass index, waist circumference, systolic blood pressure, liver enzymes, and lipid profiles. A multiple regression analysis showed that serum afamin levels were independently related to the risk of NAFLD (OR: 1.289, 95% CI, 1.141-1.456; P < 0.001). The receiver operating characteristic (ROC) analysis showed that the area under curve (AUC) of serum afamin plus the BMI for detecting NAFLD was 0.878. In participants with liver biopsies, the serum afamin plus the BMI detected NAFLD with an AUC of 0.758. In conclusion, serum afamin levels were positively associated with prevalence and risk of NAFLD, and serum afamin plus the BMI had a high diagnostic performance for NAFLD. This study provides epidemiological evidence of afamin in NAFLD.

Development and validation of an immune-related gene pairs signature in colorectal cancer.

Although the outcome of colorectal cancer (CRC) patients has improved significantly with the recent implementation of annual screening programs, reliable prognostic biomarkers are still needed due to the disease heterogeneity. Increasing pieces of evidence revealed an association between immune signature and CRC prognosis. Thus, we aim to build a robust immune-related gene pairs (IRGPs) signature that can estimate prognosis for CRC. Gene expression profiles and clinical information of CRC patients were collected from six public cohorts, divided into training cohort (n = 565) and five independent validation cohorts (n = 572, 290, 90 177 and 68, respectively). Within 1534 immune genes, a 19 IRGPs signature consisting of 36 unique genes was constructed which was significantly associated with the survival. In the validation cohorts, the IRGPs signature significantly stratified patients into high- vs low-risk groups in terms of prognosis across and within subpopulations with early stages disease and was prognostic in univariate and multivariate analyses. Several biological processes, including response to bacterium, were enriched among genes in the IRGPs signature. Macrophage M2 and mast cells were significantly higher in the high-risk risk group compared with the low-risk group. The IRGPs signature achieved a higher accuracy than commercialized multigene signatures for estimation of survival. When integrated with clinical factors such as sex and stage, the composite clinical and IRGPs signature showed improved prognostic accuracy relative to IRGPs signatures alone. In short, we developed a robust IRGPs signature for estimating prognosis in CRC, including early-stage disease, providing new insights into the identification of CRC patients with a high risk of mortality.