SUMMARY Although NOD2 is the major inflammatory bowel disease susceptibility gene, its role in colorectal tumorigenesis is poorly defined. Here, we show that Nod2-deficient mice are highly susceptible to experimental colorectal tumorigenesis independent of gut microbial dysbiosis. Interestingly, the expression of inflammatory genes and the activation of inflammatory pathways including NF-κB, ERK, and STAT3 are significantly higher in Nod2−/− mouse colons during colitis and colorectal tumorigenesis, but not at homeostasis. Consistent with higher inflammation, there is greater proliferation of epithelial cells in hyperplastic regions of Nod2−/− colons. In vitro studies demonstrate that while NOD2 activates the NF-κB and MAPK pathways in response to MDP, it inhibits TLR-mediated activation of NF-κB and MAPK. Notably, NOD2-mediated downregulation of NF-κB and MAPK is associated with the induction of IRF4. Taken together, NOD2 plays a critical role in the suppression of inflammation and tumorigenesis in the colon via downregulation of the TLR signaling pathways.

The geriatric nutritional risk index (GNRI) has been reported as a useful tool for predicting the prognosis of many diseases; however, there is currently little research on the relationship between GNRI and outcomes in elderly colorectal cancer (CRC) patients. This study aimed to explore the value of GNRI in evaluating postoperative complication risk and long-term prognosis in elderly CRC patients. Patients and Methods: The medical records of 230 CRC patients aged≥65 years who underwent surgery between January 2012 and December 2014 were retrospectively analyzed. Patients were divided into abnormal and normal GNRI groups by modified binary classification. Logistic regression analysis was used to evaluate the correlation between GNRI and complication risk. The Kaplan-Meier method with log-rank test was used to construct survival curves. The Cox proportional hazard model was used for univariate, multivariate and subgroup survival analyses to assess the relationship between GNRI and long-term prognosis. Results: Multivariate logistic regression analysis showed that GNRI (p = 0.009, HR 2.280, 95% CI: 1.224-4.247) was an independent risk factor for postoperative complications in elderly CRC patients. Kaplan-Meier survival curves revealed that the abnormal GNRI group had significantly lower disease-free survival (DFS; p = 0.005) and overall survival (OS; p=0.007) than the normal GNRI group had, especially in TNM I stage. In multivariate survival analysis, GNRI was an independent prognostic factor for DFS (p = 0.003, HR 1.842, 95% CI: 1.229-2.760) and OS (p = 0.003, HR 1.852, 95% CI: 1.231-2.787). Conclusion: GNRI is a simple and effective tool for predicting the risk of postoperative complications and the long-term prognosis of postoperative elderly CRC patients and can provide a scientific basis for early nutrition interventions in elderly CRC patients.

L3 skeletal muscle index (L3SMI) was reportedly related to postoperative outcomes. We aimed to investigate the value of L3SMI in evaluating preoperative nutritional risk and long-term prognosis in colorectal cancer (CRC) patients. We retrospectively enrolled 400 CRC patients who underwent surgery from January 2012 to December 2014. The L3SMI was calculated by preoperative computed tomography (CT) and classified into two groups by gender quartile method. We found that the CT diagnostic criteria of sarcopenia in South China population was: male ≤38.89cm 2 /m 2 , female ≤33.28cm 2 /m 2. Multivariate logistic regression analysis showed that low L3SMI was an independent risk factor for preoperative nutritional risk (p < 0.001). Kaplan-Meier survival curves showed that low status group had significantly lower disease-free survival (p = 0.004) and overall survival (p = 0.001), especially in TNM II stage. Multivariate Cox regression analysis revealed preoperative low L3SMI adversely affected disease-free survival (p < 0.001, HR 1.894 (95% CI: 1.330-2.698)), and overall survival (p < 0.001, HR 2.030 (95% CI: 1.420-2.902)). In conclusion, L3SMI is a useful supplement for screening preoperative nutritional risk and diagnosing sarcopenia, and a potential clinical indicator that can be used to predict the prognosis of CRC patients, especially TNM stage II patients. Colorectal cancer (CRC) has become the third most common malignant tumor worldwide. According to the 2018 Global Cancer Epidemiological Statistics (GLOBOCAN) database, there are approximately 1.09 million new cases of CRC (morbidity rate of 6.1%), and approximately 551,000 people (mortality rate 9.2%) die from CRC each year, making CRC the second deadliest cancer in the world 1. CRC has become the fifth most usual malignant cancer and the fourth deadliest malignant cancer in China, with the incidence gradually increasing 2. At present, surgical resection is still the mainstay curative treatment for CRC, but the 5-year survival rate for large numbers of CRC patients after R0 resection is still unsatisfactory 3,4. Therefore, prognostic factors for CRC patients are critical in guiding treatment options and follow-up strategies. In recent years, several studies have shown that sarcopenia and malnutrition seriously influence the quality of life and prognosis of cancer patients 5,6. Sarcopenia is characterized by a decline in muscle mass and function associated with aging, lack of activity and chronic diseases including various malignancies. Skeletal muscle reduction is a key feature of sarcopenia, which is also associated with poor nutrition and survival prognosis in cancer patients 7. Malnutrition is common in CRC patients, which results from a combination of malignant disease progression, host tumor responses, anticancer therapies and the direct effects of intestinal obstruction and malabsorption 8-11. In the past, weight loss and body mass index (BMI) were often used as indicators of poor nutrition and prognosis. However, with improvement in living standards, the num...

Abstract. HOXA11 antisense RNA (HOXA11-AS) is a long non-coding RNA (lncRNA) that is important in determining cancer progression. HOXA11-AS was recently identified as a novel biomarker in lung cancer progression. However, its role in colorectal cancer (CRC) remains poorly understood. The present study aimed to analyze lncRNA HOXA11-AS expression in CRC and investigate a possible association between HOXA11-AS and clinicopathological factors. HOXA11-AS expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in 84 CRC tissues and adjacent non-cancerous tissues, in addition to 3 CRC cell lines and 1 human normal colorectal cell line. The results demonstrated that HOXA11-AS expression was decreased in the CRC tissues and cell lines compared with that of the controls (P<0.05). Clinicopathological analysis indicated that low HOXA11-AS expression was significantly correlated with tumor size, advanced tumor-node-metastasis stage, lymph node metastasis and carcinoembryonic antigen level of patients with CRC (P<0.05). Furthermore, the areas under the curve (AUC) were 0.613 and 0.628 for HOXA11-AS, indicating that the lncRNA is able to distinguish CRC tissue from non-cancerous tissue, and CRC tissue with lymph node metastasis from CRC without lymph node metastasis. Therefore, HOXA11-AS may function as a potential biomarker and target for novel therapeutic strategies to treat CRC.