Abnormalities of coagulation and fibrinolysis are frequently observed in cancer patients. Emerging data suggested that plasma D-dimer and fibrinogen levels correlated with tumor stage and prognosis in several cancer types. The aim of this study is to systematically review the prognostic value of plasma D-dimer and fibrinogen in digestive cancers.We searched major database for manuscripts reporting the effect of pretreatment plasma d-dimer or fibrinogen on survival of digestive cancer patients. Revman5.3 and R were the software used for analysis. Pooled multivariable-adjusted hazard ratios (HR) for overall survival (OS) were calculated in all patients and many different subgroup analyses by stratifying on metastasis stage, tumor type, ethnicity, cutoff points and average age.37 original studies were included for analysis. Increased levels of plasma D-dimer showed stronger association with worse OS than fibrinogen in digestive cancer (HR = 2.06, 95% CI 1.79-2.38; HR = 1.60, 95% CI 1.44-1.79). The highest adverse impacts of elevated plasma D-dimer and fibrinogen on OS were revealed in colorectal cancer (HR = 2.32, 95% CI 1.89-2.85; HR = 2.20, 95% CI 1.24-3.90). The negative prognostic effects of high plasma D-dimer enhanced in metastatic patients when compared with non-metastatic digestive cancer patients, while high plasma D-dimer was more predictive non-metastatic patients.Both of pretreatment plasma D-dimer and fibrinogen were robust predictors of poor survival in digestive cancer patients with different traits. Further studies are warranted to verify their roles on cancer prognosis.
Immune checkpoint inhibitor (ICI) therapy is insensitive for Colorectal cancer (CRC) patients with microsatellite stable (MSS). Genomic data of three CRC cohort, n = 35), and the Cancer Genome Atlas (TCGA CRC cohort, n = 377), were analyzed. A cohort treated with ICIs from Memorial Sloan Kettering Cancer Center (MSKCC CRC cohort, n = 110) and two cases from the local hospital were characterized the impact of the HRR mutation on prognosis of CRC. Homologous recombination repair (HRR) gene mutations were more common in CN and HL cohorts (27.85%; 48.57%) than in TCGA CRC cohort (15.92%), especially in the MSS populations, the frequencies of HRR mutation were higher in CN and HL cohort (27.45%, 51.72%) than in TCGA cohort (6.85%). HRR mutations were associated with high tumor mutational burden (TMB-H). Although HRR mutation uncorrelated with an improved overall survival in the MSKCC CRC cohort (p = 0.97), HRR mutated patients had a significantly improved OS compared to the HRR wildtype population particularly in MSS subgroups (p = 0.0407) under ICI treatment. It probably contributed by a higher neoantigen and increased CD4+ T cell infiltration which found in the TCGA MSS HRR mutated CRC cohort. The similar phenomenon on cases was observed that MSS metastatic CRC patient with HRR mutation seemed more sensitive to ICI after multi-line chemotherapy in clinical practice than HRR wildtype. This finding suggests the feasibility of HRR mutation as an immunotherapy response predictor in MSS CRC, which highlights a potential therapeutic approach for these patients.
Since 2006, tyrosine kinase inhibitors and anti-angiogenic drugs have revolutionized the treatment of metastatic renal cell carcinoma by improving progression-free survival and overall survival. The prognostic factors in metastatic renal cell carcinoma treated by targeted therapy include anatomical, histological, clinical, biological, and molecular parameters. The accuracy of these prognostic factors are not high when applied alone. A renal cancer prognostic system that combines all these prognostic factors can improve the risk assessment of renal cancer and prognosis prediction, and thus guide clinical decision-making.
To investigate the relationship between hypertriglyceridemic waist to height ratio phenotype (HWHtR) and chronic kidney disease (CKD) in a community population in South China.A cross sectional study was conducted among 2142 residents in Zhuhai (Guangdong Province, China) from June to October of 2012. The HWHtR phenotype was defined as a waist to height ratio(WHtR) ≥0.55 and triglyceride level ≥2.0 mmol/L, based on which the participants were divided into HWHtR group and nonHWHtR group. CKD was defined as an eGFR<60 mL/min per 1.73 m2 or an ACR ≥30 mg/g. A logistic regression model was established to investigate the relationship between chronic kidney disease and HWHtR phenotype.Compared with the nonHWHtR group, the HWHtR group had a higher prevalence of chronic kidney disease (11.1% vs 33%, P<0.001). Analysis using the logistic regression model showed that HWHtR was significantly associated with CKD in the unadjusted analyses (OR=3.23, 95% CI: 2.32-4.48, P<0.001). After adjustment for age, sex, history of hypertension, history of diabetes, systolic blood pressure, diastolic blood pressure, drinking, physical exercise, education and current smoking, HWHtR was significantly associated with CKD (OR=2.36, 95% CI: 1.52-3.67, P<0.001); the association of HWHtR and CKD was still significant after further adjustment for BMI (OR=2.12, 95%CI: 1.34-3.35, P<0.001).Our finding suggests that HWHtR is associated with CKD in this community population.
Abstract Background Uncertainty still remains on the correlation of methylenetetrahydrofolate reductase ( MTHFR ) variant C677T with risk of carotid atherosclerosis (CAS), and there is a lack of reports on C677T/MTHFR in the Asian population. The association of C677T/MTHFR polymorphisms with CAS in the Chinese Han population in Chongqing was investigated in the present study. Methods Subjects ( n = 730, 214 females and 516 males, Han ethnicity) who provided an informed consent were randomly selected from the general population of Chongqing, China. Polymerase chain reaction-restriction fragment length polymorphism and Sanger sequencing genotyping assays were used to determine the MTHFR genotypes. The atherosclerosis index of the intima-media thickness (IMT) was measured by high-resolution ultrasound to evaluate the CAS. Less than 1.0 mm was considered as normal for IMT, 1.0–1.5 mm was considered as thickening, and ≥ 1.5 mm and a local bulge thickened in the lumen was considered as CAS. According to the carotid ultrasonography results, these subjects were divided into two groups: CAS-group (IMT ≥ 1.0 mm) and control group (IMT < 1.0 mm). Results The frequency of C/T heterozygotes, T/T homozygotes genotype was significantly higher in the subjects with CAS (62% vs. 36.9%; 16.2% vs. 9.5%; 47.2% vs. 27.9%, P < 0.05), while the frequency of C/C homozygotes and C allele was significantly lower (21.8% vs. 53.7%; 52.8% vs. 72.1%, P < 0.05), when compared to the control group. The risk of CAS was higher for subjects with C/T heterozygotes and T/T homozygotes (OR = 4.06, 95% CI: 2.76–5.98, P < 0.001 and OR = 3.14, 95% CI: 1.73–5.69, P < 0.001, respectively), when compared to the subjects with the C/C genotype. In the model 1 ( CT + TT versus CC ), C677T/MTHFR was significantly associated with the prevalence of CAS, and the all adjusted OR values for CAS were 3.87 (95% CI, 2.67 to 5.62) in all, 17.18 (95% CI, 7.27 to 40.49) in women and 2.57 (95% CI, 1.65 to 3.99) in men after adjusting for potential confounding factors. Conclusions The present study suggests that a mutation in the methylenetetrahydrofolate reductase gene is a risk factor of CAS in the Chinese Han population.
A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.
Obesity is associated with an increased risk of chronic kidney disease (CKD), but the best anthropometric obesity measure remains controversial. This study aimed to examine the associations of anthropometric indexes with CKD risk and which anthropometric index is a better predictor of CKD.Data was drawn from a cross-sectional study in China. We used four anthropometric indexes: body mass index (BMI), waist circumference (WC), waist-to hip ratio (WHR), and waist-to-height ratio (WHtR). CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/ min/1.73 m2 or urinary albumin to creatinine ratio (ACR) ≥ 30 mg/g. Logistic regressions were used for the analyses.1,834 participants were included in the analyses. After adjusting for potential confounders, BMI, WC and WHtR were significantly associated with CKD in men and women. The respective odd ratios for BMI (every SD increment), WC (every SD increment), and WHtR (every SD increment) were 1.46, 1.40, and 1.45 in men as well as 1.21, 1.31, and 1.38 in women. After adjusting for potential confounders, WHR was associated with CKD in women but not men. In women, the associations of WC, WHR and WHtR with CKD was independent of other MetS components. No difference in WHtR was observed between men and women.Anthropometric indexes are associated with CKD. The associations of anthropometric indexes with CKD are independent of other MetS components in women but not men. In women, central obesity indexes are better than BMI for predicting of CKD.
Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.
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