CD8
T cells play a critical role in the innate antitumour immune response. Recently, CD8
T cell dysfunction has been verified in various malignant cancers, including non-small cell lung cancer ...(NSCLC). However, the molecular biological mechanisms of CD8
T cell dysfunction in human NSCLC are still unclear.
The expression of circular ubiquitin-specific protease-7 (circUSP7) in NSCLC tissues, exosomes, and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from the culture medium of NSCLC cells and the plasma of NSCLC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit. The exosomes were then characterized by transmission electronic microscopy (TEM), NanoSight and western blotting. The role of circUSP7 in CD8
T cell dysfunction was assessed by enzyme-linked immunosorbent assay (ELISA). In vivo circular RNA (circRNA) precipitation (circRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanisms of circUSP7 in CD8
T cells. In a retrospective study, the clinical characteristics and prognostic significance of circUSP7 in NSCLC tissues were determined.
The expression levels of circUSP7 were higher in human NSCLC tissues than in matched adjacent nontumour tissues. Increased levels of circUSP7 indicate poor clinical prognosis and CD8
T cell dysfunction in patients with NSCLC. The circUSP7 found in NSCLC patient plasma is predominantly secreted by NSCLC cells in an exosomal manner, and circUSP7 inhibits IFN-γ, TNF-α, Granzyme-B and Perforin secretion by CD8
T cells. Furthermore, circUSP7 inhibits CD8
T cell function by upregulating the expression of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) via sponging miR-934. Finally, we show that circUSP7 may promote resistance to anti-PD1 immunotherapy in NSCLC patients.
Exosomal circUSP7 is predominantly secreted by NSCLC cells and contributes to immunosuppression by promoting CD8
T cell dysfunction in NSCLC. CircUSP7 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for NSCLC patients.
Epidemiological studies have reported inconsistent association between obesity and risk of bladder cancer, and the dose-response relationship between them has not been clearly defined.
We carried out ...a meta-analysis to summarize available evidence from epidemiological studies on this point. Relevant articles were identified by searching the PubMed and Web of Science databases through September 30, 2014. We pooled the relative risks from individual studies using random-effect model, and the dose-response relationship was estimated by using restricted cubic spline model.
Fifteen cohort studies with 38,072 bladder cancer cases among 14,201,500 participants were included. Compared to normal weight, the pooled relative risks and corresponding 95% confidence intervals of bladder cancer were 1.07(1.01-1.14) and 1.10(1.06-1.14) for preobese and obesity, with moderate (I² = 37.6%, P = 0.029) and low (I² = 15.5%, P = 0.241) heterogeneities between studies, respectively. In a dose-response meta-analysis, body mass index (BMI) was associated with bladder cancer risk in a linear fashion (P(non-linearity) = 0.467) and the risk increased by 4.2% for each 5 kg/m2 increase. No significant publication bias was found (P = 0.912 for Begg's test, P = 0.712 for Egger's test).
Findings from this dose-response meta-analysis suggest obesity is associated with linear-increased risk of bladder cancer.
Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case–control study to search ...for risk‐associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk odds ratios per standard deviation increase of transformed metabolites: 0.31–1.98; p values: 0.002–1.25 × 10−10. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer.
What's new?
Blood metabolites have emerged as novel biomarkers for various cancers but few studies have focused on colorectal cancer. In this prospective study, the authors identified 35 metabolites associated with colorectal cancer risk. The majority of risk‐associated metabolites were lipids, especially glycerophospholipids, pointing to a mechanistic connection between colorectal cancer and dysregulation of glycerophospholipid biology.
The relationship between consumption of cruciferous vegetables (CV) and risk of gastric cancer has been investigated by many studies, but remains controversial. We carried out a meta‐analysis to ...summarize available evidence from epidemiological studies on this point. Relevant published reports of CV intake and gastric cancer were identified using MEDLINE (PubMed), EMBASE, and Web of Science databases through to the end of September 2012. We pooled the relative risk from individual studies using a fixed‐ or random‐effects model and carried out heterogeneity and publication bias analyses. Sixteen case–control and six prospective studies were included in our analysis. When all studies were pooled, we yielded a significantly inverse association between CV (relative risk = 0.81; 95% confidence interval, 0.75–0.88) intake and gastric cancer risk, with little heterogeneity (Q = 27.27, P = 0.292, I2 = 12.0%). Specific analysis for cabbage intake yielded similar result. When separately analyzed, case–control studies of CV intake yielded significant results and the results of prospective studies showed borderline statistical significance. Moreover, significant results were consistent for high‐quality studies, for North American, European, and Asian studies, for studies on males, and for studies on non‐cardia gastric cancer. Findings from this meta‐analysis provide evidence that high intake of CV was inversely associated with the risk of gastric cancer and non‐cardia gastric cancer in humans. Further studies on other specific CV, food preparation methods, and stratified results by anatomic cancer site and histological type should be extended in the future.
Evidence from animal models suggests that dietary fatty acids have both anticancer and tumor‐promoting effects. Whether dietary fatty acids are associated with colorectal cancer (CRC) in humans ...remains inconclusive. We investigated associations between dietary fatty acids and risk of CRC among 59 986 men who participated in the Shanghai Men's Health Study (SMHS), an ongoing population‐based prospective cohort study. We identified 876 incident CRC cases in the SMHS during a mean follow‐up of 9.8 years. Associations between dietary fatty acid intake and CRC risk were evaluated by Cox proportional hazard regression analyses. Consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) was not significantly associated with CRC risk. Multivariate hazard ratios (HRs) and respective 95% confidence intervals (CIs) for Quartile 4 vs Quartile 1 were 0.92 (0.74‐1.14; Ptrend = 0.47) for SFA, 0.95 (0.79‐1.16; Ptrend = 0.74) for MUFA and 1.18 (0.95‐1.46; Ptrend = 0.21) for PUFA. No significant associations were found for total n‐6 PUFA or total n‐3 PUFA. Additionally, we performed a meta‐analysis to summarize results from the present study and 28 reports from 26 additional cohorts, which supported the overall null association between dietary fatty acid intake and CRC risk among men. Docosahexanoic acid and eicosapentaenoic acid were associated with 11% to 12% reduced risk, and linoleic acid a 19% increased risk, of CRC in the meta‐analysis of combined sexes. In conclusion, this population‐based prospective study and meta‐analysis of cohort studies found little evidence that dietary fatty acid intake was associated with risk of CRC in men.
What's new?
While diet is an important factor in colorectal cancer (CRC) risk, the contribution of specific dietary components, particularly dietary fatty acids, to CRC risk remains unclear. In this comprehensive analysis of data from a prospective cohort study and meta‐analysis of 26 additional cohorts, consumption of total, saturated, monounsaturated, or polyunsaturated fatty acids, including specific fatty acids, was not significantly associated with CRC risk in men, overall or by anatomic site. Meta‐analysis of men and women combined revealed a positive association with linoleic acid intake, while eicosapentaenoic acid and docosahexanoic acid were inversely associated with CRC risk.
Using a metabolomics approach, we systematically searched for circulating metabolite biomarkers for pancreatic cancer risk in a case‐control study nested within two prospective Shanghai cohorts. ...Included in our study were 226 incident pancreatic cancer cases and their individually‐matched controls. Untargeted mass spectrometry platforms were used to measure metabolites in blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess the associations of metabolites with pancreatic cancer risk. We identified 10 metabolites associated with pancreatic cancer, after accounting for multiple comparisons (the Benjamini‐Hochberg false discovery rate <0.05). The majority of the identified metabolites were glycerophospholipids (ORs per SD increase: 0.44–2.32; p values: 7.2 × 10−4 to 1.0 × 10−6), six of which were associated with decreased risk and one with increased risk. Additionally, levels of coumarin (OR = 1.96, p = 3.7 × 10−6) and picolinic acid (OR = 2.53, p = 5.0 × 10−5) were positively associated with pancreatic cancer risk, while tetracosanoic acid was inversely associated with risk (OR = 0.48, p = 7.16 × 10−7). Four metabolites remained statistically significant after mutual adjustment. Our study provides novel evidence that the dysregulation of glycerophospholipids may play an important role in pancreatic cancer development.
What's new?
Despite the lack of reliable biomarkers for risk assessment and early diagnosis, to date few metabolomics studies have been conducted to identify biomarkers for pancreatic cancer risk. In this nested case‐control study using pre‐diagnostic plasma samples, the authors identified ten metabolites associated with risk of pancreatic cancer after adjusting for multiple comparisons. Seven of these metabolites were glycerophospholipids, the majority of which were inversely associated with pancreatic cancer risk, providing novel evidence that glycerophospholipids dysregulation may be related to pancreatic cancer. The new metabolite biomarkers may be useful in identifying high‐risk individuals for screening and chemoprevention for this deadly malignancy.
Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease worldwide. The prevalence of T2DM is increasing rapidly in China. Understanding the contribution of modifiable lifestyle factors on T2DM ...risk is imperative to prevent the development of T2DM in China.
We examined associations between lifestyle factors including physical activity, smoking and alcohol consumption with incidence of T2DM among middle-aged and elderly men in urban Shanghai. Information on socio-demographics, lifestyle habits, dietary habits, and disease history was collected via in-person interviews. Anthropometric measurements were taken. A total of 51 464 Chinese men aged 40-74 years free of T2DM, coronary heart disease (CHD), and stroke at baseline were included in the current study. Incident T2DM was identified through follow-up surveys conducted every 2-3 years. Cox proportional hazard analyses were conducted to evaluate associations between lifestyle risk factors and incidence of T2DM.
We documented 1304 new cases of T2DM during 276 929 person-years of follow-up (average: 5.4 years). Physical activity was inversely associated with T2DM risk. Daily living, commuting, and total physical activity METs had inverse negative dose-response relationships with T2DM (P-trend = 0.0033, 0.0022, and <0.0001, respectively). Regular participation in exercise or sports reduced T2DM risk (HR = 0.86, 95%CI: 0.76-0.98). Moderate alcohol intake (1-3 drinks/day) was inversely related to T2DM risk (HR = 0.80, 95%CI: 0.67-0.94). Cigarette smoking, on the other hand, was associated with increased T2DM risk; HRs were 1.25 (95%CI: 1.00-1.56) for smoking more than 20 cigarettes per day and 1.28 (95%CI: 1.04-1.57) for smoking more than 40 pack-years.
Physical activity and moderate alcohol intake are inversely associated with T2DM risk, whereas smoking was positively associated with T2DM risk among middle-age and elderly Chinese men. Preventive measures should be developed to focus on these modifiable lifestyle habits to reduce the upward trend of T2DM.
The objective was to evaluate the effects of personal characteristics on the validation of self-reported type 2 diabetes among Chinese adults in urban Shanghai.
During 2015 through 2016, 4,322 ...participants were recruited in this validation study. We considered the criteria of diabetes verification to use the laboratory assays of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), or self-reported use of diabetic medication.
When taking diabetic medication or FPG ≥7.0 mmol/L was as identified diabetes, the measurements of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Kappa value of self-reported diabetes were 72.0%, 99.2%, 95.1%, 93.9%, and 0.78, respectively. If an additional HbA1c test was used for 708 subjects (aged <65 years), slightly lower values of sensitivity, NPV, and Kappa were observed. More potential diabetes cases were found compared to only using FPG. Subjects who were female, older, or had a family history of diabetes had sensitivity over 75% and excellent Kappa over 0.8, while the sensitivity and Kappa of opposite groups had poorer values. Specificity, PPV, and NPV were similar among groups with different demographic or disease characteristics. The prevalence of type 2 diabetes was 19.3% in the study (14.1% diagnosed diabetes, 5.2% undiagnosed diabetes). About 26.2% of subjects were pre-diabetic. Additional HbA1c test indicated an increased prevalence of undiagnosed diabetes and pre-diabetes.
Findings support self-reported diabetes is sufficiently valid to be used in large-scale, population-based epidemiologic studies. Participants with different characteristics may have different indicators in terms of validation, such as age, gender, and family history of diabetes in first-degree relatives.
To evaluate associations of premature ovarian failure (POF) with mortality and morbidity in Asian populations.
We identified 1,003 cases of POF among 36,402 postmenopausal women who participated in ...the Shanghai Women's Health Study, a population-based cohort study. Cox regression and logistic regression models were applied in data analysis.
After adjustment for potential confounding factors, we found that POF increased the risk of total and cancer-specific mortality (HR (95%CIs): 1.29 (1.08-1.54) and 1.38 (1.05-1.81), respectively). POF was also associated with high prevalence of autoimmune disease (OR (95%CI): 1.56 (1.04-2.35)) but decreased incidence of breast cancer (OR (95%CI): 0.59 (0.38-0.91)). Similar results were observed when hormone replacement therapy users were excluded from the analysis. POF is associated with high waist-to-hip ratio.
Our results suggest that women with POF experience increased mortality and that these women may benefit from heightened surveillance and appropriate interventions.
Animal studies have shown that polyunsaturated fatty acids (PUFAs) have antineoplastic and anti‐inflammatory properties. Results from epidemiologic studies on specific types of PUFAs for lung cancer ...risk, however, are inconclusive. We prospectively evaluated the association of specific types of dietary PUFA intakes and lung cancer risk in two population‐based cohort studies, the Shanghai Women's Health Study (SWHS) and Shanghai Men's Health Study (SMHS) with a total of 121,970 study participants (i.e., 65,076 women and 56,894 men). Dietary fatty acid intakes were derived from data collected at the baseline using validated food frequency questionnaires (FFQs). Cox proportional hazards model was performed to assess the association between PUFAs and lung cancer risk. Total, saturated and monounsaturated fatty acid intakes were not significantly associated with lung cancer risk. Total PUFAs intake was inversely associated with lung cancer risk HRs and respective 95% CIs for quintiles 2–5 vs quintile 1: 0.84 (0.71–0.98), 0.97 (0.83–1.13), 0.86 (0.74–1.01) and 0.85 (0.73–1.00), ptrend = 0.11. However, DHA intake was positively associated with lung cancer risk HRs and 95% CIs: 1.01 (0.86–1.19), 1.20 (1.03–1.41), 1.21 (1.03–1.42) and 1.24 (1.05–1.47), ptrend = 0.001. The ratio of n‐6 PUFAs to n‐3 PUFAs (i.e., 7:1) was inversely associated with lung cancer risk, particularly among never‐smokers and adenocarcinoma patients. Total PUFAs and the ratio between n‐6 PUFAs and n‐3 PUFAs were inversely associated with lung cancer risk. This study highlights an important public health impact of PUFA intakes toward intervention/prevention programs of lung cancer.
What's new?
Polyunsaturated fats have shown anti‐inflammatory and anti‐neoplastic activity. Here, the authors investigated whether eating polyunsaturated fatty acids (PUFAs) affects the risk of lung cancer. Using data from two population‐based cohort studies, the authors evaluated the impact of various dietary fats on lung cancer risk. Total fat, saturated fat and monounsaturated fat consumption showed no association with lung cancer risk. But risk decreased as PUFA intake increased. When they looked at the data on individual fatty acids, though, they found that higher intake of DHA, a component of fish oil supplements, correlated with higher lung cancer risk.
PDF
