Although abnormal expression of eukaryotic initiation factor 6 (eIF6) has been found in several human solid tumors, the functions and underlying mechanisms of eIF6 in the progression of colorectal cancer (CRC) still needs further elucidation. In the present study, large-scale gene analysis based on Oncomine and The Cancer Genome Atlas (TCGA) database revealed significantly higher baseline expression of eIF6 in colorectal cancer than in normal tissues. Furthermore, our Chinese cohort study revealed that high expression of eIF6 was correlated with aggressive characteristics and poor survival in CRC patients. Functional studies using magnetic nanoparticle extraction indicated that eIF6 was an oncogene in CRC cells. Regarding its mechanism, through Gene ontology (GO) and KEGG pathway analysis based on TCGA RNAseq database, we found that eIF6 can activate multiple AKT-related cancer signaling pathways, such as p-AKT\MMP1\cyclinD1\Bcl2-related signaling, to regulate cell proliferation, invasion, cell cycle and apoptosis in CRC. Collectively, these findings suggested that eIF6 can positively regulate AKT-related cancer signaling and enhance tumorigenicity in CRC, and may serve as a potential prognostic indicator and therapeutic target in CRC.

Background: There is still a lack of nomograms that can accurately predict liver metastasis and poor prognosis after neoadjuvant therapy for locally advanced rectal cancer (LARC). Effective nomograms may help clinicians better identify LARC patients with potential high-risk risks, so as to carry out more targeted monitoring, treatment and follow-up. Methods: The nomograms were based on the FOWARC trial (NCT01211210), which included 302 LARC patients who underwent neoadjuvant treatment before surgery at the Sixth Affiliated Hospital of Sun Yatsen University from 2011 to 2014. The predictive accuracy and discriminative ability of the nomograms were determined by the concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling and a prospective study on 100 patients in 2017. Results: The 3-year liver disease-free survival (LDFS) rate after neoadjuvant treatment for LARC was 91.65% (training cohort 92.22%, validation cohort 90.01%). Factors associated with LDFS were hepatitis B virus (HBV) infection, anemia, lymph node number, postoperative T stage and tumor nodule, which were all included in the nomogram for LDFS. The C-indies of the nomogram for LDFS were 0.828 and 0.845 in the training and validation cohorts. The 3-year overall survival (OS) rate was 94.14% (training cohort 94.13%, validation cohort 94.05%). Factors in the nomogram for OS were mesorectal fascia involvement (MRF), postoperative N stage, pathological differentiation, tumor nodule and neural invasion. The C-indies of the nomogram for predicting OS were 0.73 and 0.774 in the training and validation cohorts. The calibration curve for the survival probability showed good agreement between the nomogram predictions and the actual observations. Conclusions: The nomograms established in this study can effectively predict LDFS and has good clinical application potential for OS in LARC patients treated with neoadjuvant therapy.

Background: Previous studies on the effect of HBV infection on CRLM are contrary. This study identified more specific and different impacts of HBV on CRLM.Methods: A total of 3132 CRC patients were analyzed retrospectively and followed up for five years. All patients were divided into three groups: group A, HBsAg positive with HBV infection; group B, HBsAg negative with HBV infection; and group C, no HBV infection. The risk factors for SYN-CRLM, MET-CRLM, 5-year OS, and LDFS were analyzed.Results: A total of 829 patients had CRLM. SYN-CRLM was found in 425 patients. The incidence of SYN-CRLM was 16.95%, 11.60% and 13.50% (P <0.03) in groups A, B, and C, respectively. HBsAg-positive HBV infection increased the risk of SYN-CRLM (P<0.01), with a worse prognosis in group A (P<0.05). MET-CRLM was found in 404 patients. The incidence of MET-CRLM in groups A, B, and C, was 16.51%, 11.53% and 16.50% (P=0.02). HBsAg-negative HBV infection decreased the incidence of MET-CRLM (P=0.02) with a better 5-year LDFS (P=0.01), but was not related to 5-year OS (P=0.15).Conclusion: HBsAg positivity infection increased the risk of SYN-CRLM with poor prognosis. HBsAg-negative infection reduced the risk of MET-CRLM with better LDFS after surgery.

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