An evaluation model of hepatic steatosis based on CT value and serum uric acid/HDL cholesterol ratio can predict intrahepatic recurrence of colorectal cancer liver metastasis.

BACKGROUND: Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy. METHODS: Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis. RESULTS: The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients. CONCLUSION: In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy.

Serum levels of n-3 PUFA and colorectal cancer risk in Chinese population.

Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case­control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.

KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming.

Translational reprogramming is part of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, which acts to the advantage of cancer growth and development in different stress conditions, but the mechanism of ER stress-related translational reprogramming in colorectal carcinoma (CRC) progression remains unclear. Here, we identified that Krüppel-like factor 16 (KLF16) can promote CRC progression and stress tolerance through translational reprogramming. The expression of KLF16 was upregulated in CRC tissues and associated with poor prognosis for CRC patients. We found that ER stress inducers can recruit KLF16 to the nucleolus and increase its interaction with two essential proteins for nucleolar homeostasis: nucleophosmin1 (NPM1) and fibrillarin (FBL). Moreover, knockdown of KLF16 can dysregulate nucleolar homeostasis in CRC cells. Translation-reporter system and polysome profiling assays further showed that KLF16 can effectively promote cap-independent translation of ATF4, which can enhance ER-phagy and the proliferation of CRC cells. Overall, our study unveils a previously unrecognized role for KLF16 as an ER stress regulator through mediating translational reprogramming to enhance the stress tolerance of CRC cells and provides a potential therapeutic vulnerability.

Public awareness of colorectal cancer in the Chinese population: An online cross-sectional survey study.

OBJECTIVES: To investigate public awareness of colorectal cancer (three components: total knowledge, confidence and anticipated delay) in the Chinese population, to explore factors associated with total knowledge and to elucidate relationships among three components of public awareness of colorectal cancer. METHODS: We recruited 562 adult Chinese participants with no history of colorectal cancer between March and May 2020 by convenience sampling method. Data were collected online using a self-designed demographic questionnaire and a simplified Chinese version of the Bowel Cancer Awareness Measure. Univariate analysis and multivariate linear regression were applied. RESULTS: The mean score for total knowledge was 10.56 (SD: 5.89). Over half of the participants (58.2%) lacked confidence about detecting warning signs. For 42.7% of participants, the anticipated delay was not within the acceptable range (2 weeks). Totally eight demographic variables were identified as significant predictors of total knowledge, accounting for 36.2% of the variance. Total knowledge was positively correlated with confidence (r = 0.126, p < 0.01) and negatively associated with anticipated delay (F = 8.891, p < 0.01). CONCLUSION: Public awareness of colorectal cancer was low in the Chinese population. Hence, educational interventions targeted for improving knowledge, enhancing individuals' confidence in detecting symptoms and reducing barriers to seeking medical help may be urgently required.

Association between Dietary Zinc and Selenium Intake, Oxidative Stress-Related Gene Polymorphism, and Colorectal Cancer Risk in Chinese Population - A Case-Control Study.

Zinc and selenium may protect against colorectal cancer (CRC) progression through their anti-oxidative effects. This study examined the independent and combined effect of dietary zinc and selenium intake, and polymorphisms of the oxidative stress-related genes (superoxide dismutase 1, superoxide dismutase 2, glutathione peroxidase, and catalase) on CRC risk in a Chinese case-control study. A total of 493 cases and 498 sex and age-matched controls were randomly selected from an ongoing case-control study. Dietary information was assessed through face-to-face interviews using a validated food frequency questionnaire. Multiplex PCR-ligase detection reaction was used for genotyping the target SNPs. Multivariable logistic regression was used to estimate the odds ratios (ORs) and 95% confidence interval (CI). Intake of selenium was found to be inversely associated with CRC risk, while zinc was not associated with CRC risk. The ORs (95% CI) for the highest vs. the lowest quartile were 0.42 (95% CI 0.28, 0.64, Ptrend < 0.001) for selenium and 0.96 (95% CI 0.63, 1.47, Ptrend = 0.505) for zinc. Combined effect was observed between zinc and SOD1 rs4998557 on CRC risk (Pinteraction < 0.05). This study identified a novel diet-gene interaction in the oxidative stress pathway on CRC risk in Chinese population.

Exploration of the methods of establishing the minimum clinical important difference based on anchor and its application in the quality of life measurement scale QLICP-ES (V2.0) for esophageal cancer.

BACKGROUND: The development of the minimum clinical important difference (MCID) can make it easier for researchers or doctors to judge the significance of research results and the effect of intervention measures, and improve the evaluation system of efficacy. This paper is aimed to calculate the MCID based on anchor and to develop MCID for esophageal cancer scale (QLICP-ES). METHODS: The item Q29 (How do you evaluate your overall health in the past week with 7 grades answers from 1 very poor to 7 excellent)of EORTC QLQ-C30 was used as the subjective anchor to calculate the score difference between each domain at discharge and admission. MCID was established according to two standards, "one grade difference"(A) and "at least one grade difference"(B), and developed by three methods: anchor-based method, ROC curve method and multiple linear regression models. In terms of anchor-based method, the mean of the absolute value of the difference before and after treatments is MCID. The point with the best sensitivity and specificity-Yorden index at the ROC curve is MCID for ROC curve method. In contrast, the predicted mean value based on a multiple linear regression model and the parameters of each factor is MCID. RESULTS: Most of the correlation coefficients of Q29 and various domains of the QLICP-ES were higher than 0.30. The rank of MCID values determined by different methods and standards were as follows: standard B > standard A, anchor-based method > ROC curve method > multiple linear regression models. The recommended MCID values of physical domain, psychological domain, social domain, common symptom and side-effects domain, the specific domain and the overall of the QLICP-ES were 7.8, 9.7, 4.7, 3.6, 4.3, 2.3 and 2.9, respectively. CONCLUSION: Different methods have their own advantages and disadvantages, and also different definitions and standards can be adopted according to research purposes and methods. A lot of different MCID values were presented in this paper so that it can be easy and convenient to select by users.

Interactions Between Vitamin D and Calcium Intake, Vitamin D Receptor Genetic Polymorphisms, and Colorectal Cancer Risk.

BACKGROUND: Vitamin D has anticarcinogenic properties and acts through vitamin D receptor (VDR) to carry out its functions. AIMS: This study explored the independent and combined effects of dietary vitamin D and calcium, and VDR genetic polymorphisms on colorectal cancer risk in a Chinese population. METHODS: This ongoing case-control study recruited 488 cases with histologically confirmed colorectal cancer and 496 sex- and age-matched controls. Vitamin D and calcium intakes were assessed by a validated food frequency questionnaire, and VDR genotype was conducted for Fok I (rs2228570), Bsm I (rs1544410), Apa I (rs7975232), and Taq I (rs731236). Unconditional logistic regression was used to calculate odds ratio and 95% confidence interval after adjusting for various confounders. RESULTS: No significant association was found between Fok I, Bsm I, Apa I, Taq I, and colorectal cancer risk. Higher intakes of dietary vitamin D and calcium were associated with 47% and 50% reduction in colorectal cancer risk. Significant interaction was observed between dietary vitamin D intake and Apa I polymorphisms in relation to colorectal cancer risk (Pinteraction = 0.006). Subjects with higher dietary vitamin D intake and mutant Apa I A allele had a substantially decreased risk of colorectal cancer compared to Apa I aa carriers with lower vitamin D intake. CONCLUSIONS: Our study supports that Apa I may interact with dietary vitamin D intake on colorectal cancer risk. However, no interactions were found between dietary vitamin D or calcium intakes and Fok I, Bsm I, and Taq I in relation to colorectal cancer risk.

Dietary B vitamin and methionine intakes and risk for colorectal cancer: a case-control study in China.

B vitamins (including folate, vitamin B2, vitamin B6 and vitamin B12) and methionine are essential for methylation reactions, nucleotide synthesis, DNA stability and DNA repair. However, epidemiological evidence among Chinese populations is limited. The objective of this study was to evaluate B vitamins and methionine in relation to colorectal cancer risk in a Chinese population. A case-control study was conducted from July 2010 to April 2019. A total of 2502 patients with colorectal cancer were recruited along with 2538 age- (5-year interval) and sex-matched controls. Dietary data were collected using a validated FFQ. Multivariable logistic regression was used to assess OR and 95 % CI. The intake of folate, vitamin B2, vitamin B6 and vitamin B12 was inversely associated with colorectal cancer risk. The multivariable OR for the highest quartile v. the lowest quartile were 0·62 (95 % CI 0·51, 0·74; Ptrend < 0·001) for folate, 0·46 (95 % CI 0·38, 0·55; Ptrend < 0·001) for vitamin B2, 0·55 (95 % CI 0·46, 0·76; Ptrend < 0·001) for vitamin B6 and 0·72 (95 % CI 0·60, 0·86; Ptrend < 0·001) for vitamin B12. No statistically significant association was found between methionine intake and colorectal cancer risk. Stratified analysis by sex showed that the inverse associations between vitamin B12 and methionine intake and colorectal cancer risk were found only among women. This study indicated that higher intake of folate, vitamin B2, vitamin B6 and vitamin B12 was associated with decreased risk of colorectal cancer in a Chinese population.

Higher intakes of dietary vitamin D, calcium and dairy products are inversely associated with the risk of colorectal cancer: a case-control study in China.

The effects of dietary vitamin D, Ca and dairy products intakes on colorectal cancer risk remain controversial. The present study investigated the association between these dietary intakes and the risk of colorectal cancer in Guangdong, China. From July 2010 to December 2018, 2380 patients with colorectal cancer and 2389 sex- and age-matched controls were recruited. Dietary intake data were collected through face-to-face interviews using a validated FFQ. Unconditional multivariable logistic regression models were used to calculate the OR and 95 % CI after adjusting for various confounders. Higher dietary vitamin D and Ca intakes were associated with 43 and 52 % reductions in colorectal cancer risk, with OR of 0·57 (95 % CI 0·46, 0·70) and 0·48 (95 % CI 0·39, 0·61), respectively, for the highest quartile (v. the lowest quartile) intakes. A statistically significant inverse association was observed between total dairy product intake and colorectal cancer risk, with an adjusted OR of 0·32 (95 % CI 0·27, 0·39) for the highest v. the lowest tertile. Subjects who drank milk had a 48 % lower risk of colorectal cancer than those who did not (OR 0·52, 95 % CI 0·45, 0·59). The inverse associations of dietary vitamin D, Ca, total dairy products and milk intakes with the risk of colorectal cancer were independent of sex and cancer site. Our study supports the protective effects of high dietary vitamin D, Ca and dairy products intakes against colorectal cancer in a Chinese population.

Different forms and sources of iron in relation to colorectal cancer risk: a case-control study in China.

Few studies have examined the association of various types of Fe with colorectal cancer risk. The aim of this study was to investigate different forms and sources of Fe in relation to colorectal cancer risk in a Chinese population. A total of 2138 patients with colorectal cancer and 2144 sex- and age-matched (5-year interval) controls were recruited from July 2010 to November 2017. Dietary information was assessed by face-to-face interviews using a validated FFQ. Multivariable logistic regression was used to estimate the OR and 95 % CI on models. Intake of Fe from plants and Fe from white meat were inversely associated with the risk of colorectal cancer, while haem Fe and Fe from red meat were positively associated with colorectal cancer risk. The multivariable OR for the highest quartile v. the lowest quartile were 0·72 (95 % CI 0·59, 0·87, P trend<0·001) for Fe from plants, 0·54 (95 % CI 0·45, 0·66, P trend<0·001) for Fe from white meat, 1·26 (95 % CI 1·04, 1·53, P trend=0·005) for haem Fe and 1·83 (95 % CI 1·49, 2·24, P trend<0·001) for Fe from red meat intake, respectively. However, no significant association was found between the consumption of total dietary Fe, non-haem Fe, Fe from meat and colorectal cancer risk. This study showed that lower intake of Fe from plants and white meat, as well as higher intake of haem Fe and Fe from red meat, were associated with colorectal cancer risk in a Chinese population.

Carbohydrate, dietary glycaemic index and glycaemic load, and colorectal cancer risk: a case-control study in China.

A carbohydrate-rich diet results in hyperglycaemia and hyperinsulinaemia; it may further induce the carcinogenesis of colorectal cancer. However, epidemiological evidence among Chinese population is quite limited. The aim of this study was to investigate total carbohydrate, non-fibre carbohydrate, total fibre, starch, dietary glycaemic index (GI) and glycaemic load (GL) in relation to colorectal cancer risk in Chinese population. A case-control study was conducted from July 2010 to April 2017, recruiting 1944 eligible colorectal cancer cases and 2027 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. There was no clear association between total carbohydrate intake and colorectal cancer risk. The adjusted OR was 0·85 (95 % CI 0·70, 1·03, P trend=0·08) comparing the highest with the lowest quartile. Total fibre was related to a 53 % reduction in colorectal cancer risk (adjusted ORquartile 4 v. 1 0·47; 95 % CI 0·39, 0·58). However, dietary GI was positively associated with colorectal cancer risk, with an adjusted ORquartile 4 v. 1 of 3·10 (95 % CI 2·51, 3·85). No significant association was found between the intakes of non-fibre carbohydrate, starch and dietary GL and colorectal cancer risk. This study indicated that dietary GI was positively associated with colorectal cancer risk, but no evidence supported that total carbohydrate, non-fibre carbohydrate, starch or high dietary GL intake were related to an increased risk of colorectal cancer in a Chinese population.

Distinct patterns and prognostic values of tumor-infiltrating macrophages in hepatocellular carcinoma and gastric cancer.

BACKGROUND: Macrophages (Mφs) constitute a major component of the leukocyte infiltrate and perform distinct roles in different tumor microenvironments. This study aimed to characterize the distribution, composition and prognostic value of Mφs in hepatocellular carcinoma (HCC) and gastric cancer (GC). METHODS: Immunohistochemistry and immunofluorescence were used to identify Mφ subsets in HCC and GC tissues. Kaplan-Meier analysis and Cox regression models were applied to estimate the overall survival (OS) for HCC and GC patients. RESULTS: The results showed that the density of Mφs decreased in the intra-tumor region (IT) of HCC, but remarkably increased in the IT of GC, as compared with their non-tumor regions (NT). In HCC, most CD68+ Mφs were CD204+ and CD169+ cells in the NT region; however, there was a significant decrease in the percentage of CD169+ Mφ in the IT region. In contrast, CD68+ Mφs comprised a smaller percentage of CD204+ than the CD169+ subpopulation in the NT region, while more CD204+ but fewer CD169+ cells were present in the IT region of GC. The density of CD204+ Mφs correlated with poor prognosis in HCC, and CD169+ Mφs were associated with good survival in both HCC and GC. Moreover, the combination of low numbers of CD204+ and high numbers of CD169+ Mφs was associated with improved OS in both GC and HCC. CONCLUSIONS: Mφs display tissue-specific distributions and distinct composition patterns in HCC and GC tissues. Our results suggested that different types of tumors might use diverse strategies to reconstitute Mφ patterns to promote tumor progression.

Association between phytosterol intake and colorectal cancer risk: a case-control study.

A study in rodent models showed that phytosterols protected against colon carcinogenesis, probably by inhibiting dysregulated cell cycle progression and inducing cellular apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk are quite limited. The aim of this study was to investigate dietary phytosterol intake in relation to colorectal cancer risk in the Chinese population. A case-control study was conducted from July 2010 to June 2016, recruiting 1802 eligible colorectal cancer cases plus 1813 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. A higher total intake of phytosterols was found to be associated with a 50 % reduction in colorectal cancer risk. After adjusting for various confounders, the OR of the highest quartile intake compared with the lowest quartile intake was 0·50 (95 % CI 0·41, 0·61, P trend<0·01) for total phytosterols. An inverse association was also found between the consumption of ß-sitosterol, campesterol, campestanol and colorectal cancer risk. However, stigmasterol intake was related to an increased risk of colorectal cancer. No statistically significant association was found between ß-sitostanol and colorectal cancer risk. Stratified analysis by sex showed that the positive association of stigmasterol intake with colorectal cancer risk was found only in women. These data indicated that the consumption of total phytosterols, ß-sitosterol, campesterol and campestanol is inversely associated with colorectal cancer risk in a Chinese population.

Flavonoid intake from vegetables and fruits is inversely associated with colorectal cancer risk: a case-control study in China.

Flavonoids may play an important role in the protective effects of vegetables, fruits and tea against colorectal cancer. However, associations between flavonoids and colorectal cancer risk are inconsistent, and a few studies have evaluated the effect of flavonoids from different dietary sources separately. This study aimed to evaluate associations of flavonoids intake from different dietary sources with colorectal cancer risk in a Chinese population. From July 2010 to December 2015, 1632 eligible colorectal cancer cases and 1632 frequency-matched controls (age and sex) completed in-person interviews. A validated FFQ was used to estimate dietary flavonoids intake. Multivariate logistical regression models were used to calculate the OR and 95 % CI of colorectal cancer risk after adjusting for various confounders. No significant association was found between total flavonoids and colorectal cancer risk, with an adjusted OR of 1·06 (95 % CI 0·85, 1·32) comparing the highest with the lowest quartile. Anthocyanidins, flavanones and flavones intakes from total diet were found to be inversely associated with colorectal cancer risk. Compared with the lowest quartile, the adjusted OR for the highest quartile were 0·80 (95 % CI 0·64, 1·00) for anthocyanidins, 0·28 (95 % CI 0·22, 0·36) for flavanones and 0·54 (95 % CI 0·43, 0·67) for flavones. All subclasses of flavonoids from vegetables and fruits were inversely associated with colorectal cancer. However, no significant association was found between tea flavonoids and colorectal cancer risk. These data indicate that specific flavonoids, specifically flavonoids from vegetables and fruits, may be linked with the reduced risk of colorectal cancer.

High consumption of vegetable and fruit colour groups is inversely associated with the risk of colorectal cancer: a case-control study.

The colour of the edible portion of vegetables and fruit reflects the presence of specific micronutrients and phytochemicals. No existing studies have examined the relationship between the intake of vegetable and fruit colour groups and the risk of colorectal cancer. The present study, therefore, aimed to investigate these associations in a Chinese population. A case-control study was conducted between July 2010 and July 2014 in Guangzhou, China, in which 1057 consecutively recruited cases of colorectal cancer were frequency-matched to 1057 controls by age (5-year interval), sex and residence (rural/urban). A validated FFQ was used to collect dietary information during face-to-face interviews. Vegetables and fruit were classified into four groups according to the colour of their primarily edible parts: green; orange/yellow; red/purple; white. Unconditional logistic regression models were used to estimate the OR and 95 % CI. A higher consumption of orange/yellow, red/purple and white vegetables and fruit was inversely associated with the risk of colorectal cancer, with adjusted OR of 0·16 (95 % CI 0·12, 0·22) for orange/yellow, 0·23 (95 % CI 0·17, 0·31) for red/purple and 0·53 (95 % CI 0·40, 0·70) for white vegetables and fruit when the highest and lowest quartiles were compared. Total vegetable intake and total fruit intake have also been found to be inversely associated with colorectal cancer risk. However, the intake of green vegetable and fruit was not associated with colorectal cancer risk. The results of the present study, therefore, suggest that a greater intake of orange/yellow, red/purple and white vegetables and fruit is inversely associated with the risk of colorectal cancer.

Higher intake of carotenoid is associated with a lower risk of colorectal cancer in Chinese adults: a case-control study.

PURPOSE: The associations between specific carotenoid intake and colorectal cancer risk remain inconsistent. The aim of this study was to examine the association between specific dietary carotenoid intake with colorectal cancer risk in Chinese adults. METHOD: From July 2010 to October 2013, 845 eligible colorectal cancer cases and 845 frequency-matched controls (age and sex) completed in-person interviews. A validated food frequency questionnaire was used to estimate dietary intake. Multivariate logistical regression models were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CIs) of colorectal cancer risk after adjusting for various confounders. RESULTS: A strong inverse association was found between ß-cryptoxanthin intake and colorectal cancer risk. Compared with the lowest quartile, the highest quartile intake showed a risk reduction of 77% (OR 0.23, 95% CI 0.17-0.33, P trend < 0.01) after adjustment for various confounding variables. The inverse associations were also observed for α-carotene (OR 0.50, 95% CI 0.37-0.68, P trend < 0.01), ß-carotene (OR 0.67, 95% CI 0.49-0.91, P trend < 0.01), and lycopene (OR 0.51, 95% CI 0.37-0.70, P trend < 0.01). There was no statistically significant association between lutein/zeaxanthin intake and colorectal cancer risk. These findings were consistent across cancer site, sources of controls, and smoking status. The inverse associations between dietary α-carotene, ß-cryptoxanthin, and lycopene intake and colorectal cancer risk were found in both males and females, while inverse associations between ß-carotene intake and colorectal cancer risk were only observed in males. CONCLUSIONS: Consumption of α-carotene, ß-carotene, ß-cryptoxanthin, and lycopene was inversely associated with colorectal cancer risk. No significant association was found between lutein/zeaxanthin intake and colorectal cancer risk.

Dietary fiber and fiber fraction intakes and colorectal cancer risk in Chinese adults.

Few studies have been conducted in Chinese adults to investigate the effect of fiber intake on colorectal cancer risk. The present study aimed to examine the associations of dietary fiber and fiber fraction intakes with colorectal cancer risk in Chinese adults. A total of 613 cases with colorectal cancer were consecutively recruited between July 2010 and October 2012 and frequency matched to 613 controls by age (5-yr interval) and gender. Dietary information was collected through a validated food frequency questionnaire by face-to-face interviews. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for potential confounders. Total dietary fiber and fiber fraction intakes were found to be inversely associated with colorectal cancer risk. Compared with the lowest quartile, the adjusted ORs (95% CIs) for the highest quartile were 0.38 (0.27-0.55) for total dietary fiber, 0.45 (0.32-0.64) for vegetable fiber, and 0.41 (0.28-0.58) for fruit fiber, respectively. In addition, no significant association was found between soy fiber intake and colorectal cancer risk. This study showed that a high intake of dietary fiber, particularly derived from vegetables and fruit, was inversely associated with colorectal cancer risk in Chinese adults.

Docosahexaenoic acid inhibits the invasion and migration of colorectal cancer by reversing EMT through the TGF-ß1/Smad signaling pathway.

The primary cause of mortality in colorectal cancer (CRC) patients is tumor metastasis. The epithelial-mesenchymal transition (EMT) stands out as a crucial factor promoting the metastasis of CRC. Previous findings suggest a potential inhibitory effect of docosahexaenoic acid (DHA) on CRC metastasis, but the precise mechanism remains unknown, this study aims to explore this issue. We assessed metastasis and recurrence, all-cause mortality, and cancer-related mortality rates according to DHA intake in independent CRC cohorts (n = 367) by survival analysis. The ability of DHA to block CRC cell migration and invasion was tested using transwell and wound-healing assays. The regulation of EMT marker genes in CRC by DHA was detected by quantitative real-time PCR (qPCR) and immunoblotting, and the effect of DHA on the TGF-ß1/Smad signaling pathway was further investigated. These cellular findings were validated using a subcutaneous CRC mouse model. Survival analyses showed that lower DHA intake was associated with a higher risk of CRC metastasis and a poorer prognosis. In vitro experiments showed that DHA inhibits the TGF-ß1/Smad signaling pathway and regulates downstream transcription factors, thereby reversing the EMT and inhibiting invasion and migration. In the mouse model, dietary DHA supplementation effectively increased blood DHA concentrations and inhibited CRC metastasis. Our study demonstrated that DHA inhibits CRC invasion and metastasis by inhibiting the TGF-ß1/Smad signaling pathway. Increased intake of DHA among CRC patients may provide additional benefits to the prognosis of colorectal cancer.

Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer.

Bevacizumab plays an important role in the first and second line treatment for metastatic colorectal cancer (CRC). And induction of hypoxia and the tumors response to it plays an important role in determining the efficacy of antiangiogenic therapy while the connection between them remains unclear. Here, we found that lactate accumulated in the tumor environment of CRC and acted as substrates for histone lactylation, and this process was further induced by cellular enhanced glycolysis in hypoxia. We determined that CRC patients resistant to bevacizumab treatment presented with elevated levels of histone lactylation and inhibition of histone lactylation efficiently suppressed CRC tumorigenesis, progression and survival in hypoxia. Histone lactylation promoted the transcription of RUBCNL/Pacer, facilitating autophagosome maturation through interacting with BECN1 (beclin 1) and mediating the recruitment and function of the class III phosphatidylinositol 3-kinase complex, which had a crucial role in hypoxic cancer cells proliferation and survival. Moreover, combining inhibition of histone lactylation and macroautophagy/autophagy with bevacizumab treatment demonstrated remarkable treatment efficacy in bevacizumab-resistance patients-derived pre-clinical models. These findings delivered a new exploration and important supplement of metabolic reprogramming-epigenetic regulation, and provided a new strategy for improving clinical efficacy of bevacizumab in CRC by inhibition of histone lactylation.Abbreviations: 2-DG: 2-deoxy-D-glucose; BECN1: beclin 1; CQ: chloroquine; CRC: colorectal cancer; DMOG: dimethyloxalylglycine; H3K18la: histone H3 lysine 18 lactylation; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; Nala: sodium lactate; PDO: patient-derived orgnoid; PDX: patient-derived xenograft; RUBCNL/Pacer: rubicon like autophagy enhancer; SQSTM1/p62: sequestosome 1.

Serum biomarkers REG1A and REG3A combined with the traditional CEA represent a novel nomogram for the screening and risk stratification of colorectal cancer.

BACKGROUND: To develop and validate a serum protein nomogram for colorectal cancer (CRC) screening. METHODS: The serum protein characteristics were extracted from an independent sample containing 30 colorectal cancer and 12 polyp tissues along with their paired samples, and different serum protein expression profiles were validated using RNA microarrays. The prediction model was developed in a training cohort that included 1345 patients clinicopathologically confirmed CRC and 518 normal participants, and data were gathered from November 2011 to January 2017. The lasso logistic regression model was employed for features selection and serum nomogram building. An internal validation cohort containing 576 CRC patients and 222 normal participants was assessed. RESULTS: Serum signatures containing 27 secreted proteins were significantly differentially expressed in polyps and CRC compared to paired normal tissue, and REG family proteins were selected as potential predictors. The C-index of the nomogram1 (based on Lasso logistic regression model) which contains REG1A, REG3A, CEA and age was 0.913 (95% CI, 0.899 to 0.928) and was well calibrated. Addition of CA199 to the nomogram failed to show incremental prognostic value, as shown in nomogram2 (based on logistic regression model). Application of the nomogram1 in the independent validation cohort had similar discrimination (C-index, 0.912 [95% CI, 0.890 to 0.934]) and good calibration. The decision curve (DCA) and clinical impact curve (ICI) analysis demonstrated that nomogram1 was clinically useful. CONCLUSIONS: This study presents a serum nomogram that included REG1A, REG3A, CEA and age, which can be convenient for screening of colorectal cancer.