Adherence to the low-fat diet pattern reduces the risk of lung cancer in American adults aged 55 years and above: a prospective cohort study.

OBJECTIVES: There is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older. DESIGN: A prospective cohort study with a mean follow-up time of 8.8 years. SETTING AND PARTICIPANTS: This study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer. METHODS: Dietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: During a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66-0.89), NSCLC (HR, 0.79; 95% CI, 0.67-0.93), and SCLC (HR, 0.59; 95% CI, 0.38-0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60-0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10-1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20-3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes. CONCLUSIONS: Our findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.

Carbohydrate quality, not quantity, linked to reduced colorectal cancer incidence and mortality in US populations: evidence from a prospective study.

BACKGROUND: Carbohydrates have been implicated in colorectal cancer (CRC) risk, but the specific impact of carbohydrate quality and quantity on CRC susceptibility in US populations remains unclear. METHODS: We followed 101,694 participants from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The carbohydrate quality index (CQI) and low-carbohydrate diet score (LCDs) were used to evaluate the daily carbohydrate quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to compute HRs and 95% CIs for incident CRC and related death. Subgroup analyses were conducted to identify potential effect modifiers. RESULTS: During follow-up, we documented 1085 incident cases of CRC, of whom 311 died from CRC. Individuals in the highest compared with the lowest quartiles of CQI had a lower CRC incidence (Q4 vs Q1: HR 0.80, 95% CI 0.67-0.96, Ptrend = 0.012) and mortality (Q4 vs Q1: HR 0.61, 95% CI 0.44-0.86, Ptrend = 0.004). The inverse association between CQI and CRC risk was observed for distal colon and rectum but not for proximal colon cancer. Regarding mortality, this association was only significant for rectum cancer. Subgroup analyses indicated this inverse association of CQI with CRC risk was only observed in participants with lower LCDs. No significant associations were found between LCDs and CRC incidence or mortality. CONCLUSIONS: Our findings suggest focusing on higher quality, rather than restricting the quantity, of carbohydrate consumption may be an effective approach to reduce the risk of CRC in the US population, particularly for distal colon and rectal cancers.

Association between Dietary Anthocyanidins and Biliary Cancer Risk in 98,458 Participants: Results from a Prospective Study.

BACKGROUND: Previous studies have suggested anthocyanidins or anthocyanidin-rich foods and extracts exhibit protective effects against various cancers. However, the relationship between dietary anthocyanidins and the risk of biliary cancer remains uncertain. METHODS: This study used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate the relationship between total anthocyanidins intake and biliary cancer incidence. Cox regression analysis was conducted to estimate HRs and corresponding 95% confidence intervals (CI) for the incidence of biliary cancer, with adjustments made for confounding factors. A restricted cubic spline model was employed to examine the dose-response relationship. In addition, subgroup and sensitivity analyses were conducted to evaluate potential interactions and test the model's robustness. RESULTS: During 8.9 years and 872,645.3 person-years of follow-up, 95 cases of biliary cancer were observed. The incidence rate of biliary cancer in this study was 11 cases per 100,000 person-years. Using the fully adjusted Cox regression model, the inverse association was observed between total anthocyanidins intake and the risk of biliary cancer (HR Q4 vs..Q1: 0.52; 95% CI: 0.29-0.91; Ptrend = 0.043). This association remained significant in sensitivity analyses. A linear dose-response relationship (Pnonlinearity = 0.118) and potential interaction with drinking status (Pinteraction = 0.033) were identified. CONCLUSIONS: This study provides evidence of an inverse association between total anthocyanidins intake and biliary cancer incidence. IMPACT: Our study found a total anthocyanidin-rich diet was associated with a reduced risk of biliary cancer in Americans ages 55 to 74 years.

Compliance with the EAT-Lancet diet and risk of colorectal cancer: a prospective cohort study in 98,415 American adults.

Background: The EAT-Lancet diet (ELD) is a recommended dietary pattern for achieving simultaneous improvements in both individual health and environmental sustainability. While research on the association between ELD and colorectal cancer (CRC) remains scarce, the potential impact of nutrition on CRC prevention and progression is a topic of growing interest. This study aims to investigate the relationship between adherence to the ELD and the risk of CRC, shedding light on the role of nutrition in CRC prevention. Methods: A total of 98,415 participants were included. A Diet History Questionnaire (DHQ) was used to collect dietary information, and an ELD score was used to assess adherence to ELD. Higher scores indicated greater adherence. Cox hazard regression analyses were conducted to examine whether there were associations between the ELD score and CRC risk. The restricted cubic spline (RCS) model was used to further explore the dose-response association between the ELD score and CRC incidence. Subgroup analyses were conducted to identify potential modifiers that interacted with ELD on CRC incidence, and sensitivity analyses were performed to evaluate the robustness of the established association. Results: During a mean follow-up of 8.82 years, a total of 1,054 CRC cases were documented. We found a statistically significant correlation between the ELD score and CRC risk (Q4 vs. Q1: HR 0.81, 95% CI 0.67-0.98; P for trend = 0.034) after adjusting for potential confounders. No statistically significant associations were discovered between ELD adherence and CRC by anatomical site. Subgroup analyses found no interactional factor, sensitivity analyses, and the RCS model showed a robustness and linearity association (P-linearity >0.05). Conclusion: We concluded that adherence to ELD contributes to the prevention of CRC.

Association of diabetes risk reduction diet with renal cancer risk in 101,755 participants: a prospective study.

BACKGROUND: There is little prospective evidence exists about whether adherence to a diabetes risk reduction diet (DRRD) is related to a significant reduction in renal cancer risk. We sought to clarify whether adherence to DRRD was associated with a reduced risk of renal cancer in a US population. METHODS: A population-based cohort of 101,755 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A DRRD score was calculated to assess adherence to this dietary pattern, where increased scores indicated greater adherence. The relationship between DRRD score and risk of renal cancer was assessed based on the hazard ratios (HRs) and 95% confidence intervals (CIs), which were both calculated using Cox regression. Non-linear association was determined through restricted cubic spline regression. Potential effect modifiers were identified through subgroup analyses. RESULTS: Over a mean follow-up of 8.8 years, 446 renal cancers were detected. In this analysis, the fully adjusted model depicted a notable 29% reduction in the risk of renal cancer among individuals in the highest quartile of DRRD score in comparison with the lowest quartile individuals (HRQ4 vs. Q1: 0.71; 95% CI = 0.54, 0.94; Ptrend = 0.008). This association remained consistent across a series of sensitivity analyses. A non-linear inverse dose-response association between renal cancer risk with DRRD score was observed (Pnonlinearity = 0.026). Subgroup analyses showed that this favorable link was more prominent in participants with low Healthy Eating Index-2015 (Pinteraction = 0.015). Regarding the individual components of DRRD, a decrease in the risk of renal cancer was linked to increased intake of cereal fiber and whole fruit, and lower sugar-sweetened beverage consumption (all Ptrend < 0.05). CONCLUSIONS: Our findings indicate that individuals adhering to DRRD are associated with a reduction in the risk of renal cancer.

Adherence to diabetes risk reduction diet and the risk of head and neck cancer: a prospective study of 101,755 American adults.

Background: Adherence to the diabetes risk reduction diet (DRRD) may potentially reduce the risk of developing head and neck cancer (HNC) as the diet includes fruits and limits red and processed meats, known risk factors for HNC. However, there is currently no epidemiological research to investigate this potential association. Methods: The present study utilized data on demographics, lifestyles, medications, and diets of participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to explore the potential association between adherence to DRRD and the risk of HNC. We used a DRRD score to evaluate adherence to the dietary pattern and employed Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HNC risk. Several subgroup analyses were carried out to identify potential effect modifiers, and multiple sensitivity analyses were performed to evaluate the stability of the correlation. The nine components of the DRRD was assessed separately for its association with the risk of HNC. Results: During a mean follow up of 8.84 years, 279 cases of HNC were observed. DDRD score was found to be inversely associated with the risk of HNC (HR Q4 vs. Q1: 0.582; 95% CI: 0.396, 0.856; p = 0.005 for trend) in a linear dose-response manner (p = 0.211 for non-linearity). Subgroup analysis indicated this inverse correlation was more pronounced among participants who had never smoked (HRQ4 vs. Q1: 0.193; 95% CI: 0.073, 0.511; p < 0.001 for trend) compared to current or former smokers (p = 0.044 for interaction). The primary association of DDRD and HNC risk remained robust after several sensitivity analyses. Regarding the individual components of DRRD, an inverse association was also observed between the risk of HNC and increased intake of cereal fiber and whole fruit (all p < 0.05 for trend). Conclusion: Our findings provide evidence that following the DRRD pattern may reduce the risk of NHC, especially for non-smokers.

Association between adherence to Eat-Lancet diet and incidence and mortality of lung cancer: A prospective cohort study.

Previous research has shown that adhering to the Eat-Lancet diet (ELD) is associated with a lower risk of chronic diseases and mortality. However, the associations between ELD and lung cancer incidence and mortality are unclear. To address this gap, we conducted a prospective cohort study involving 101,755 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial in the USA. The ELD score was utilized to assess compliance with the ELD, with higher scores indicating greater compliance. We employed Cox regression analyses to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ELD score with the incidence and mortality of lung cancer and its subtypes. In addition, sensitivity analyses were performed to ensure the robustness of our findings. In total, 1706 cases of lung cancer and 1217 lung cancer-associated deaths were recorded during the study period. Our analysis revealed that higher ELD scores were significantly associated with a reduced incidence (HRQuartile 4 vs. Quartile 1 : 0.73; 95% CI: 0.60, 0.89; ptrend = 0.001) and mortality (HRQuartile 4 vs. Quartile 1 : 0.74; 95% CI: 0.59, 0.93; ptrend = 0.005) of lung cancer in a dose-response manner (all pnonlinearity > 0.05). The reliability of these results was supported by sensitivity analyses. Notably, these associations were primarily observed in non-small-cell lung cancer. In conclusion, our findings suggest that adherence to the ELD may be associated with a reduced risk of lung cancer incidence and mortality.

Molecular characteristics, clinical significance, and immune landscape of extracellular matrix remodeling-associated genes in colorectal cancer.

Background: Extracellular matrix (ECM) remodeling is one of the hallmark events in cancer and has been shown to be closely related to tumor immunity. Immunotherapy has evolved as an important tool to treat various cancers and improve patient prognosis. The positive response to immunotherapy relies on the unique interaction between cancer and the tumor microenvironment (TME). However, the relationship between ECM remodeling and clinical outcomes, immune cell infiltration, and immunotherapy in colorectal cancer (CRC) remains unknown. Methods: We systematically evaluated 69 ECM remodeling-associated genes (EAGs) and comprehensively identified interactions between ECM remodeling and prognosis and the immune microenvironment in CRC patients. The EAG_score was used to quantify the subtype of ECM remodeling in patients. We then assessed their value in predicting prognosis and responding to treatment in CRC. Results: After elaborating the molecular characteristics of ECM remodeling-related genes in CRC patients, a model consisting of two ECM remodeling-related genes (MEIS2, SLC2A3) was developed for predicting the prognosis of CRC patients, Receiver Operating Characteristic (ROC) and Kaplan-Meier (K-M) analysis verified its reliable predictive ability. Furthermore, we created a highly reliable nomogram to enhance the clinical feasibility of the EAG_score. Significantly differences in TME and immune function, such as macrophages and CD8+ T cells, were observed between high- and low-risk CRC patients. In addition, drug sensitivity is also strongly related to EAG_score. Conclusion: Overall, we developed a prognostic model associated with ECM remodeling, provided meaningful clinical implications for immunotherapy, and facilitated individualized treatment for CRC patients. Further studies are needed to reveal the underlying mechanisms of ECM remodeling in CRC.

Association between sulfur microbial diet and the risk of colorectal cancer precursors in older adults.

Background: Sulfur microbial diet (SMD), related to the enrichment of sulfur-metabolizing gut bacteria, has been confirmed to be linked to an elevated risk of early-onset colorectal adenoma in young females. However, it remains unclear whether SMD is associated with the risk of colorectal adenoma in older people, who are at greater risk for colorectal cancer. Methods: All data on participants in this study were retrieved from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening test. Participants' adherence to this dietary pattern was assessed using SMD score. Hazard ratios (HR) and 95% confidence intervals (CI) were adopted in Cox proportional hazards regression models to assess the link between SMD score and the incidence of colorectal adenoma in participants included in the study. Specific stratified analyses were constructed to assess whether this association changed in different conditions, whereas the robustness of the association was examined through sensitivity analyses. Results: The mean baseline age of participants was 62.1 (SD 5.2) years (range 54.0-75.0 years). During 19,468,589 person-years of follow-up, 992 colorectal adenoma cases were documented in a total of 17,627 included participants. In a fully adjusted model, an increased risk of colorectal adenoma was determined in participants in the highest quartile of SMD score in comparison with those in the lowest quartile (HRquartile4 vs. HRquartile1 = 1.23; 95% CI: 1.02, 1.47; p = 0.017 for trend). This positive association between SMD score and adenoma risk was more evident in participants who were current or former smokers (p = 0.029 for interaction). Conclusion: In this study, our results support a role for the SMD in the carcinogenicity of colorectal cancer precursors among older adults. Nevertheless, these results require validation through more research.

Exosomal ACADM sensitizes gemcitabine-resistance through modulating fatty acid metabolism and ferroptosis in pancreatic cancer.

This study aimed to evaluate the potential of exosomes from cancer cells to predict chemoresistance in pancreatic cancer (PC) and explore the molecular mechanisms through RNA-sequencing and mass spectrometry. We sought to understand the connection between the exosomal Medium-chain acyl-CoA dehydrogenase (ACADM) level and the reaction to gemcitabine in vivo and in patients with PC. We employed loss-of-function, gain-of-function, metabolome mass spectrometry, and xenograft models to investigate the effect of exosomal ACADM in chemoresistance in PC. Our results showed that the molecules involved in lipid metabolism in exosomes vary between PC cells with different gemcitabine sensitivity. Exosomal ACADM (Exo-ACADM) was strongly correlated with gemcitabine sensitivity in vivo, which can be used as a predictor for postoperative gemcitabine chemosensitivity in pancreatic patients. Moreover, ACADM was found to regulate the gemcitabine response by affecting ferroptosis through Glutathione peroxidase 4 (GPX4) and mevalonate pathways. It was also observed that ACADM increased the consumption of unsaturated fatty acids and decreased intracellular lipid peroxides and reactive oxygen species (ROS) levels. In conclusion, this research suggests that Exo-ACADM may be a viable biomarker for predicting the responsiveness of patients to chemotherapy.

Adherence to the Paleolithic diet and Paleolithic-like lifestyle reduce the risk of colorectal cancer in the United States: a prospective cohort study.

BACKGROUND: The plant-based paleolithic diet (PD) and the paleolithic-like lifestyle (PLL) may reduce the risk of chronic diseases, including colorectal adenomas. These dietary and lifestyle approaches are proposed to exert their effects through mechanisms such as reducing inflammation, oxidative stress, and insulin levels. However, whether PD and PLL is associated with the risk of colorectal cancer (CRC) has not been determined. METHODS: A cohort of 74,721 individuals who participated in the PLCO study were included in this analysis. Adherence to the PD and PLL was assessed using PD and PLL scores, where higher scores indicated greater adherence. Multivariable Cox models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subsites (proximal colon cancer and distal CRC). Subgroup analyses were conducted to identify potential effect modifiers. RESULTS: During a mean follow-up of 9.2 years, a total of 694 CRC cases were identified. Participants in the highest compared with the lowest quartiles of PD score had a lower risk of CRC (Q4 vs Q1: HR 0.76, 95% CI 0.61-0.95, Ptrend = 0.009) and proximal colon cancer (Q4 vs Q1: HR 0.73, 95% CI 0.55-0.97, Ptrend = 0.02). A stronger inverse association was observed for PLL score with the risk of CRC (Q4 vs Q1: HR 0.64, 95% CI 0.51-0.81, Ptrend < 0.001), proximal colon (Q4 vs Q1: HR 0.62, 95% CI 0.46-0.83, Ptrend = 0.001) and distal CRC (Q4 vs Q1: HR 0.69, 95% CI 0.48-0.98, Ptrend = 0.03). Subgroup analyses revealed the inverse association of PD score with the risk of CRC was more pronounced in participants with BMI < 30 (Q4 vs Q1: HR 0.68, 95% CI 0.53-0.87) than in those with BMI ≥ 30 (Q4 vs Q1: HR 1.07, 95% CI 0.68-1.67) (Pinteraction = 0.02). CONCLUSIONS: Our findings suggest that adhering to the PD and PLL could be a new option to reduce CRC risk.

Low-fat dairy consumption and the risk of lung cancer: A large prospective cohort study.

BACKGROUND: Despite the possible contribution of dairy products to the development or prevention of cancers, there is a lack of epidemiological evidence linking low-fat dairy consumption to the risk of developing lung cancer. This research was conducted to fill this knowledge gap. METHODS: The data for this research were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The Cox proportional risk model was employed to evaluate the link between low-fat dairy consumption and the risk of developing lung cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were measured in both unadjusted and adjusted models. A series of predefined subgroup analyses were performed to identify potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: The study included data from 98,459 individuals. During a total of 869,807.9 follow-up person-years, 1642 cases of lung cancer were observed, with an incidence of 0.189 cases for every 100 person-years. In the fully adjusted model, participants in the highest quartile of low-fat dairy consumption had a significantly decreased risk of lung cancer compared to the ones in the lowest quartile (HRquartile 4 vs. 1 : 0.769, 95% CI: 0.664, 0.891, ptrend = 0.005). The restricted cubic spline plot revealed an inverse nonlinear dose-response relationship between low-fat dairy consumption and lung cancer risk (pnonlinearity = 0.008). Subgroup analyses demonstrated that the inverse association was stronger among participants with higher daily caloric intake (pinteraction = 0.031). Various sensitivity analyses produced consistent results. CONCLUSION: Consuming more low-fat dairy products is significantly linked to a reduced risk of developing lung cancer, indicating that an appropriate increase in the use of low-fat dairy products may help prevent lung cancer.

Association between dietary approaches to stop hypertension eating pattern and lung cancer risk in 98,459 participants: results from a large prospective study.

Background: Dietary approaches to stop hypertension (DASH) eating pattern is linked to anti-inflammatory responses and antioxidation, which overlap with the pathogenesis of lung cancer. However, there is insufficient epidemiological evidence to link this dietary pattern to lung cancer risk conclusively. Aim: To determine if adherence to the DASH diet is linked to a lower risk of developing lung cancer in a large prospective study. Methodology: The data of participants were retrieved from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A DASH score was calculated based on 8 dietary components to reflect adherence to DASH, with greater scores representing higher adherence. Three Cox proportional hazards models were constructed to analyze the association between DASH scores and lung cancer risk, including an unadjusted model and two adjusted models (model 1 for demographics and model 2 for fully confounding factors). A restricted cubic spline plot was utilized to illustrate the likelihood of developing lung cancer across the entire range of DASH scores. The association between each of the 8 DASH components and the risk of lung cancer was assessed separately. Several subgroup analyses were conducted to identify potential modifiers, and several sensitivity analyses were performed to verify the robustness of the findings. Results: The study involved 98,459 individuals in total. The mean (standard deviation) DASH score was 24.00 (4.62) points, along with the mean follow-up period of 8.84 (1.94) years. Lung cancer was identified in 1642 cases over 869807.9 person-years of follow-up, and the overall incidence rate was 0.189 cases/100 person-years. Participants in the highest quartile in the fully adjusted model had a relatively decreased risk of developing lung cancer in comparison to those in the lowest quartile (HRquartile 4 versus 1: 0.647; 95% CI: 0.557, 0.752; Ptrend < 0.001). The restricted cubic spline plot demonstrated that DASH score and lung cancer risk were inversely associated and had a linear dose-response relationship (Pnon-linear = 0.944). According to subgroup analyses, those who were current or former smokers had a stronger inverse connection than those who never smoked (Pinteraction = 0.013). The results remained robust after several sensitivity analyses. Conclusion: The risk of lung cancer was inversely associated with DASH scores in the US population. This suggests that following the DASH pattern can help prevent lung cancer, especially for current or former smokers. More epidemiological evidence from other regions and populations is needed to confirm our findings.

Predictive factors on postoperative venous thromboembolism after minimally invasive colorectal cancer surgery: a retrospective observational study.

BACKGROUND: Venous thromboembolism (VTE) is a serious and preventable postoperative complication. However, the predictive significance of perioperative biochemical parameters for VTE after minimally invasive colorectal cancer surgery remains unclear. METHODS: A total of 149 patients undergoing minimally invasive colorectal cancer surgery were collected between October 2021 and October 2022. Biochemical parameters related to preoperative and postoperative day 1, day 3, and day 5 were collected, including D-Dimer, mean platelet volume (MPV), and maximum amplitude (MA) of thromboelastography (TEG). Receiver operating characteristic (ROC) curves were used to explore the predictive powers of meaningful biochemical parameters for postoperative VTE, and calibration curves were used to assess predictive accuracy. RESULTS: The overall cumulative incidence of VTE was 8.1% (12/149). The preoperative and postoperative day 3 D-Dimer, postoperative day 3, and day 5 MPV, and postoperative day 1, day 3, and day 5 TEG-MA was significantly higher in the VTE group than in the non-VTE group (P < 0.05). The results of both the ROC curve and the calibration curve indicated that these meaningful D-Dimer, MPV, and TEG-MA had moderate discrimination and consistency for postoperative VTE. CONCLUSIONS: D-Dimer, MPV, and TEG-MA may predict postoperative VTE in patients undergoing minimally invasive surgery for colorectal cancer at specific times in the perioperative period.

Maternal Serum tRNA-Derived Fragments (tRFs) as Potential Candidates for Diagnosis of Fetal Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) is one of the most predominant birth defects that causes infant death worldwide. The timely and successful surgical treatment of CHD on newborns after delivery requires accurate detection and reliable diagnosis during pregnancy. However, there are no biomarkers that can serve as an early diagnostic factor for CHD patients. tRNA-derived fragments (tRFs) have been reported to play an important role in the occurrence and progression of numerous diseases, but their roles in CHD remains unknown. METHODS: High-throughput sequencing was performed on the peripheral blood of pregnant women with an abnormal fetal heart and a normal fetal heart, and 728 differentially expressed tRFs/tiRNAs were identified, among which the top 18 tRFs/tiRNAs were selected as predictive biomarkers of CHD. Then, a quantitative reverse transcriptase polymerase chain reaction verified the expression of tRFs/tiRNAs in more clinical samples, and the correlation between tRFs/tiRNAs abnormalities and CHD was analyzed. RESULTS: tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2 may be promising biomarkers. Through further bioinformatics analysis, we predicted that TRF-58:744-GLy-GCC-1 could induce CHD by influencing biological metabolic processes. CONCLUSIONS: Our results provide a theoretical basis for the abnormally expressed tRF-58:74-Gly-GCC-1 in maternal peripheral blood as a new potential biomarker for the accurate diagnosis of CHD during pregnancy.

Assessment of stromal SCD-induced drug resistance of PDAC using 3D-printed zPDX model chips.

Lipid metabolism is extensively reprogrammed in pancreatic ductal adenocarcinoma (PDAC). Stearoyl-coenzyme A desaturase (SCD) is a critical lipid regulator that was unexplored in PDAC. Here, we characterized the existence of cancer-associated fibroblasts (CAFs) with high SCD expression, and revealed them as an unfavorable prognostic factor. Therefore, primary CAFs and pancreatic cancer cells were harvested and genetically labeled. The mixture of CAFs and cancer cells were co-injected into scd-/-; prkdc-/-, or hIGF1/INS-expressing zebrafish to generate patient-derived xenograft models (zPDX). The models were aligned in 3D-printed chips for semi-automatic drug administration and high-throughput scanning. The results showed that chaperoning of the SCD-high CAFs significantly improved the drug resistance of pancreatic cancer cells against gemcitabine and cisplatin, while the administration of SCD inhibitors neutralized the protective effect. Our studies revealed the prognostic and therapeutic value of stromal SCD in PDAC, and proposed the application of zPDX model chips for drug testing.

ANXA10 is a prognostic biomarker and suppressor of hepatocellular carcinoma: a bioinformatics analysis and experimental validation.

Liver hepatocellular carcinoma (LIHC) is one of the main cancers worldwide and has high morbidity and mortality rates. Although previous studies have shown that ANXA10 is expressed at low levels in LIHC tumor tissues, the biological function of ANXA10 in LIHC is still unclear. Therefore, we utilized TCGA, TIMER, GEPIA2, TISIDB, LinkedOmics, ssGSEA algorithms and CIBERSORT methodology to preliminarily evaluate the potential mechanism of ANXA10 in LIHC. In vitro experiments were used to further verify some functions of ANXA10. Consequently, we found that ANXA10 mRNA/protein expression was downregulated in LIHC tissue compared to normal tissue. ANXA10 was significantly linked with clinicopathological features, immunocytes, multiple cancer-related pathways, m6A modification and a ceRNA network. A three-gene prognostic signature rooted in ANXA10-related immunomodulators was determined and found to be an independent prognostic predictor. A nomogram was constructed to predict survival with good accuracy. Additionally, in vitro trials revealed that ANXA10 upregulation inhibited LIHC cell proliferation and migration. This study reveals that ANXA10 may serve as a prognostic marker and promising therapeutic target in LIHC clinical practice through various biologic functions.

Genotype-guided model significantly improves accuracy of tacrolimus initial dosing after liver transplantation.

Background: The initial dose of tacrolimus after liver transplantation (LT) is critical for rapidly achieving the steady state of the drug concentration, minimizing the potential adverse reactions and warranting long-term patient prognosis. We aimed to develop and validate a genotype-guided model for determining personalized initial dose of tacrolimus. Methods: By combining pharmacokinetic modeling, pharmacogenomic analysis and multiple statistical methods, we developed a genotype-guided model to predict individualized tacrolimus initial dose after LT in the discovery (n = 150) and validation cohorts (n = 97) respectively. This model was further validated in a prospective, randomized and single-blind clinical trial from August, 2021 to February, 2022 (n = 40, ChiCTR2100050288). Findings: Our model included donor's and recipient's genotypes, recipient's weight and total bilirubin, which achieved an area under the curve of receiver operating characteristic curve (AUC of ROC) of 0.88 and 0.79 in the discovery and validation cohorts, respectively. We found that patients who were given tacrolimus within the recommended concentration range (RCR) (4-10 ng/mL), the new-onset metabolic syndromes are lower, especially for new-onset diabetes (p = 0.043). In the clinical trial, compared to those in experience-based (EB) group, patients in the model-based (MB) group were more likely to achieving the RCR (75% vs 40%, p = 0.025) with a more variable individualized dose (0.023-0.096 mg/kg/day vs 0.045-0.057 mg/kg/day). Moreover, significantly fewer medication adjustments were required for the MB group than the EB group (2.75 ± 2.01 vs 6.05 ± 3.35, p = 0.001). Interpretation: Our genotype-based model significantly improved the initial dosing accuracy of tacrolimus and reduced the number of medication adjustments, which are critical for improving the prognosis of LT patients. Funding: National Natural Science Foundation of China, Shanghai three-year action plan, National Science and Technology Major Project of China.

Association between oxidative stress exposure and colorectal cancer risk in 98,395 participants: results from a prospective study.

Background: The intricate role of oxidative stress (OS) in colorectal cancer (CRC) initiation is underscored by an imbalance between pro-oxidants and antioxidants. Utilizing the Oxidative Balance Score (OBS) as a metric, this study aims to investigate the association between OS exposure and CRC risk, while also examining potential sex-specific differences in a large U.S. cohort. Methods: The study included 98,395 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. To construct the OBS, 14 dietary and lifestyle factors intricately associated with oxidative stress were quantified. A higher OBS value indicated a more favorable oxidative balance pattern or diminished OS exposure. Due to sex-specific differences in OBS, associations were evaluated separately for men and women based on Cox regression analysis. Subgroup analyses were conducted to elucidate potential modifiers. Results: During 867,963.4 person-years of follow-up, 1,054 CRCs occurred. The mean (SD) age and OBS were 65.52 (5.73) years and 14.09 (3.95) points, respectively. In the fully adjusted Cox model, we observed an inverse association between OBS and CRC incidence in women (HRQ5vsQ1: 0.72; 95% CI: 0.52, 0.99; P for trend = 0.018) but not men. Subgroup analyses revealed the inverse association was more pronounced among women without versus with a family history of CRC (HRQ5 vsQ1: 0.66, 95% CI: 0.47-0.93; P for trend = 0.001; P for interaction = 0.001). The results remained robust after several sensitivity analyses. Conclusion: Higher OBS was associated with lower CRC risk in women but not men; this inverse association was stronger among women without a family history of CRC. These findings suggest exposure to OS may confer sex-specific CRC risk effects, especially for women without a family history of CRC.

Association between low-fat diet and liver cancer risk in 98,455 participants: Results from a prospective study.

Background: Low-fat diet reduces the risk of chronic metabolic diseases such as obesity and diabetes, which exhibit overlapping mechanisms with liver cancer. However, the association between low-fat diet and liver cancer risk remains unclear. Aim: To investigate whether adherence to low-fat diet is associated with a reduced risk of liver cancer in a prospective study. Materials and methods: Data of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A low-fat diet score was calculated to reflect adherence to low-fat dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for liver cancer incidence with adjustment for potential covariates. Restricted cubic spline model was used to characterize liver cancer risk across the full range of the low-fat diet score. Prespecified subgroup analyses were used to identify potential impact modifiers. Sensitivity analyses were performed to test the robustness of this association. Results: A total of 98,455 participants were included in the present analysis. The mean (standard deviation) age, low-fat diet score, and follow-up time were 65.52 (5.73) years, 14.99 (6.27) points, and 8.86 (1.90) years, respectively. During 872639.5 person-years of follow-up, 91 liver cancers occurred, with an overall incidence rate of 0.01 cases per 100 person-years. In the fully adjusted Cox model, the highest versus the lowest quartile of low-fat diet score was found to be associated with a reduced risk of liver cancer (HR Q4 vs. Q1: 0.458; 95% CI: 0.218, 0.964; P = 0.035 for trend), which remained associated through a series of sensitivity analyses. The restricted cubic spline model showed a linear dose-response association between low-fat diet score and liver cancer incidence (p = 0.482 for non-linear). Subgroup analyses did not show significant interaction between low-fat diet score and potential impact modifiers in the incidence of liver cancer. Conclusion: In this study, low-fat diet score is associated with reduced liver cancer risk in the US population, indicating that adherence to low-fat diet may be helpful for liver cancer prevention. Future studies should validate our findings in other populations.