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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 case–control 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.

Plant-based diets are associated with a lower risk of colorectal cancer, but the risk might differ by the quality of plant-based diets. This study aimed to investigate the association between different types of plant-based dietary patterns and colorectal cancer risk in the Chinese population. We conducted a case-control study with 2799 eligible colorectal cancer cases and 2799 sex- and age-matched controls in Guangzhou, China. A validated food frequency questionnaire was used to collect dietary data, from which we derived plant-based diet indices, including the plant-based diet index (PDI), the healthy PDI (hPDI), and the unhealthy PDI (uPDI). The PDI, hPDI, and uPDI assess the adherence to overall, healthy, and unhealthy plant-based dietary patterns, respectively. The odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal cancer risk were estimated using unconditional logistic regression models. Higher adherence to the PDI, particularly the hPDI, was associated with a lower risk of colorectal cancer, whereas greater adherence to the uPDI was associated with a higher risk of colorectal cancer. Compared with the lowest quintile, the adjusted ORs in the highest quintile were 0.79 (95% CI: 0.66-0.95) for the PDI, 0.45 (95% CI: 0.38-0.55) for the hPDI, and 1.45 (95% CI: 1.18-1.78) for the hPDI, respectively. In stratified analysis, the inverse association between the PDI and colorectal cancer risk was not observed in women, and the positive association between the uPDI and colorectal cancer risk was not observed in men. In conclusion, these results support recommendations that shifting to a healthy plant-based dietary pattern is important for the prevention of colorectal cancer, particularly in the Chinese population that habitually consumes plant foods.

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.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.

The majority of colorectal cancers (CRCs) are hormone‑dependent. Thus, endocrine therapy has become an attractive strategy to treat CRC. The aim of the present study was to investigate the inhibitory effect of combined tamoxifen (TAM) plus β‑estradiol (E2) treatment on human DLD‑1 CRC cells. The human DLD‑1 CRC cell line was treated with different concentrations of TAM, β‑estradiol, or a combination of these two agents. Cell viability was assessed using an MTT assay, while apoptosis was detected using flow cytometry analysis. Alterations in the RNA and protein levels of the apoptosis‑associated factors cyclin D1 and survivin were measured in the treated DLD‑1 cells using semi‑quantitative polymerase chain reaction (sqPCR) and western blot analyses. Alterations in cellular migration ability were monitored using a Transwell migration assay. Treatment with TAM, β‑estradiol and TAM plus β‑estradiol inhibited DLD‑1 cell viability. The flow cytometry results revealed that these drugs promoted cell apoptosis, and the Transwell migration assay results indicated that the reduction in cell migration was greater in the TAM+E2 treatment group when compared with each treatment alone. sqPCR and western blot analysis results demonstrated that TAM, E2 and a combination of the two affected survivin expression based on the drug concentration and the treatment duration; however, they demonstrated no significant effect on cyclin D1 expression. In conclusion, treatment of DLD‑1 cells with TAM, β‑estradiol, or a combination of these two drugs, inhibited cell viability and migration, promoted cell apoptosis, and reduced the mRNA and protein expression levels of survivin in a dose‑ and time‑dependent manner. These results provide novel experimental basis for hormonal adjuvant therapy for the treatment of CRC.

Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.

To explore the associated biomarkers influencing recurrence, metastasis and prognosis in patients with gastrointestinal stromal tumors (GIST) after complete resection.Tumor tissue samples of 148 patients with GIST undergoing complete resection from January 1990 to December 2008 in Sun Yat-sen University Cancer Center were collected. The expressions of Ki-67, E-cadherin, MMP7, CD44, nm23, P53, survivin, Cyclin D1, COX-2, and VEGF in tumor tissue samples were detected by tissue microarray and immunohistochemistry (IHC). The association of above factors expressions with recurrence, metastasis and prognosis was examined.Log-rank test showed that Ki-67, E-cadherin, MMP7, CD44, P53 and survivin were associated to disease-free duration after complete GIST resection (all P0.05), and the Ki-67, E-cadherin, P53 and survivin were associated to overall survival (all P0.05). Cox multivariate analysis revealed that disease-free survival was associated with Ki-67, CD44 and P53 (all P0.05), and the overall survival was only associated with Ki-67 (P0.05).Ki-67, CD44 and P53 are closely associated with recurrence and metastasis after complete GIST resection, and Ki-67 can predict the prognosis of GIST.

Purpose: CD169 was first identified on macrophages (Mϕ) and linked to antigen presentation. Here, we showed CD169 expression on some CD8+ T lymphocytes in regional lymph nodes (LNs) and investigated the function and clinical relevance of CD169+CD8+ T cells in tumor-draining LNs of colorectal cancer (CRC) patients. Experimental design: Fresh tumor-draining LN tissues from 39 randomly enrolled patients were assessed by flow cytometry for activation and differentiation of CD169+CD8+ T cells and T cell-mediated killing of tumor cells. In total, 114 tumor-draining LN paraffin sections from CRC patients were analyzed by multiple-color immunofluorescence for CD169+CD8+ T cell distribution and clinical values. The prognostic significance of CD169+CD8+ T cells was evaluated by Kaplan–Meier analysis. Results: A fraction of CD8+ T cells in regional LNs, but not peripheral blood, tonsils, or tumors, expressed surface CD169. In situ detection of draining LNs revealed preferential localization of CD169+CD8+ T cells to subcapsular sinus and interfollicular regions, closely associated with CD169+ Mϕ. CD169+CD8+ T cell ratios were significantly lower in peri-tumor LNs than distant-tumor LNs. CD169+CD8+ T cells predominantly expressed activation markers (CD69, HLA-DR, PD-1) with slightly lower CD45RA and CD62L levels. They produced high granzyme B, perforin, TNF-α, and IFNγ levels, and promoted tumor-killing efficiency ex vitro. Moreover, CD169+CD8+ T cells infiltrating tumor-draining LNs decreased with disease progression and were strongly associated with CRC patient survival. Conclusions: We identified novel activated/cytolytic CD169+CD8+ T cells selectively present in regional LNs, potentially serving as a powerful prognostic factor and indicator for selecting patients for immunotherapy.

Estrogen receptor beta (ERβ) and TROP2 expressed in colon carcinoma and might play an important role there. We explored the relationship of ERβ and TROP2 expression with the prognosis of early-stage colon cancer. ERβ and TROP2 levels were assessed by immunohistochemistry in normal mucosa and tumoral tissues from 220 Chinese patients with T(3)N(0)M(0) (stage IIa) and T(4)N(0)M(0) (stage IIb) colon cancer in the Cancer Center, Sun Yat-sen University, who underwent curative surgical resection between 1995 and 2003. The Cox proportional hazards regression model was applied to analyze the overall survival (OS) data, and the ROC curve, Kaplan-Meier estimate, log rank test, and Jackknife method were used to show the effect of ERβ and TROP2 expression at different stages of cancer. The 5-year survival rates were not significantly different between the patients with stage IIa and stage IIb colon cancer (83 vs. 80 %, respectively). The high expression of ERβ was related to decreasing OS in stage IIa and stage IIb colon cancer, while the high expression of TROP2 was related to decreasing OS in stage IIb colon cancer. The expression of ERβ and TROP2 has tumor-suppressive and tumor-promoting effect in stage IIa and stage IIb colon cancer, respectively.

The correlation of ERβ/CD44 expression and progression of patients with stage II of colon cancer were explored in this work. A total of 220 paraffin-embedded specimens with stage II colon cancer from 1995 to 2003 were included for assessing ERβ and CD44 by immunohistochemistry in normal mucosa and tumor tissues. Kaplen-Meier method, log-rank test, and the Cox proportional hazards regression model were used to analyze the overall survival data. ROC curve was used to describe the capacity of variables in prognosis prediction. Jackknife method was used to perform cross validation of predictions. The survival rates were significantly different between the patients with high expression and low expression of CD44-tumor tissues (61 % vs. 90 %, p < 0.0001) and between the patients with high expression and low expression of ERβ-tumor tissue (99 % vs. 36 %, p < 0.0001), respectively. In addition, the interaction between expression of ERβ and CD44 was found that the impact of CD44 to the overall survive appeared only when expression of ERβ was low; and the high expression of ERβ-tumor could be regarded as a protective factor for overall survival. This study suggest that low expression of ERβ-tumor and high expression of CD44-tumor are risk factors for overall survival in patients with stage II colon cancer.