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 highvs 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. ARTICLE HISTORY
Background To determine the metabolic characteristics of patients with colon cancer (CC) and rectal cancer (RC) using gas chromatography‐mass spectrometry (GC‐MS)‐based metabolomics. Methods In this study, serum samples were collected from 22 CC patients and 23 RC patients preoperatively and postoperatively and 45 healthy volunteers (HVs), and subjected to metabolomics analysis by GC‐MS. Differential metabolites in the preoperative RC and CC samples and HVs were identified as potential biomarkers and evaluated for their utilities by receiver operating characteristic analyses. Results The different metabolic markers between CC and RC patients were identified, which may assist in distinguishing the two types of cancers. The area under the curve (AUC) was 0.805 for combination of d‐glucose and d‐mannose for CC diagnosis, and 0.889 for combination of 2‐aminobutanoic acid, 3‐hydroxypyridine, d‐glucose, d‐mannose, isoleucine, l‐tryptophan, urea, and uric acid for RC diagnosis. The combinations of metabolite markers showed a better predictability than CEA and CA199 two commonly used protein markers for CRC diagnosis in clinical practice. Combining the metabolite markers with these two protein markers effectively improved the diagnostic accuracy with the AUC reaching 0.936 and 0.937 for CC and RC diagnosis, respectively. Conclusions Metabolic profiles are different in the blood samples between CC and RC patients. The study has established a panel of metabolic markers as a predictive and multiplexing signature for CC and RC diagnosis.
Background. Some studies have reported that renal dysfunction is associated with poor prognosis in cirrhotic patients. Serum cystatin C (CysC) is an accurate biomarker for early renal dysfunction. This study aimed to assess the prognostic value of serum CysC levels in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). Methods. This retrospective study included 75 subjects who had been diagnosed with HBV-DeCi. The association between serum CysC and prognosis was estimated by receiver operating characteristic curve analysis and a multivariable logistic regression model. Results. Serum CysC levels were higher in nonsurvivors than in survivors and were positively correlated with model for end-stage liver disease (MELD) scores. In multivariate analysis, CysC and the MELD score were independent prognostic factors in all HBV-DeCi patients. However, only serum CysC was an independent factor predicting mortality in patients with normal creatinine levels. Conclusions. These data suggest that high serum CysC levels can be considered an independent biomarker of 3-month mortality in patients with HBV-DeCi.
Hepatitis B virus (HBV) infection is an important health problem worldwide and HBV-infected patients can develop liver failure, liver cirrhosis, and hepatocellular carcinoma, resulting in an annual death toll of more than 1 million patients. 1,2 In China, HBV is the major cause of liver cirrhosis, and approximately 3% of HBV-infected patients with compensated cirrhosis develop decompensated cirrhosis (DeCi) each year, with a 5-year survival rate of only 15%. [3][4][5] Liver transplantation is an only reliable life-prolonging intervention for patients suffering from this condition. However, a shortage of donor livers and serious post-transplantation complications have limited its application. Therefore, identification of specific biomarkers that allow early assessment of prognosis of HBV-DeCi patients has gained importance in clinical practice.It is well known that the systemic inflammatory status plays an important role in the pathogenesis of HBV infection. Several studies have demonstrated that inflammation is relatively common in patients with advanced cirrhosis and associated with poor outcomes. 6,7 Monocyte-to-HDL-cholesterol (HDL-C) ratio (MHR) was a newly proposed inflammatory biomarker. 8 Recently, MHR was reported to be closely associated with coronary heart disease, [9][10][11] atrial fibrillation, 12,13 hypertension, 14 chronic kidney disease, 15 and cerebrovascular accidents. 16 However, no studies have investigated
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