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Exosome-mediated microRNAs (miRNAs) are closely related to the occurrence, development, invasion, metastasis, therapeutic resistance, diagnosis and treatment of malignant tumors. Guide-strand miRNA and passenger-strand miRNA (miRNA*) exist in miRNA processing, but the function of passenger-strand miRNA is often overlooked. In this study, we attempted to identify functional miRNA*s in exosomes derived from human colon cancer SW620 cells. miRNA expression profiles of human normal colonic epithelial cells NCM460 and colon cancer cells SW620 were compared by high-throughput sequencing. According to the sequencing results, we defined two sets of differentially expressed miRNAs: "high in exosome and high in cell" (HEHC) and "high in exosome but low in cell" (HELC). As passenger-strand miRNAs, miR-2277-3p and miR-26b-3p, which belong to different sets, have diametrically opposite functions. MiR-2277-3p promotes proliferation, migration, and invasion of SW620 cells by targeting NUPR1L, while miR-26b-3p exerts an inhibitory effect by targeting PFDN1. Using exosomes as transport vectors, the effect of exosomes rich in miR-2277-3p on cells is consistent with the effect of liposome-transfected overexpressed miR-2277-3p, resulting in a cancer-promoting effect. However, exosomes rich in miR-26b-3p did not have a tumor suppressor effect. Further analysis revealed that exosomes rich in miR-2277-3p also had a high abundance of integrin β4. Altering the abundance of integrin β4 in exosomes changes the ability of exosomes to be taken up by cells, thereby altering the paracrine effects of exosomes. In summary, we revealed the fact that a large number of passenger-strand miRNAs exist in exosomes of colon cancer cells, these miRNAs are preliminarily categorized into two sets, and miR-2277-3p and miR-26b-3p, as representatives of each set, showed opposite functions. In addition, we revealed that integrin β4 is a marker of exosome heterogeneity in colon cancer cells, which directly correlates with the ability of exosomes to be uptaken by cells of the same kind, thus regulating the paracrine effect of exosomes.

BackgroundThe purpose of this study is to compare and evaluate the security and efficacy of 3D vs 2D laparoscopy in rectal cancer treatment.MethodsForty-six patients who suffered from rectal cancer and went on laparoscopic radical resection of rectal carcinoma in Peking University Shougang Hospital from Feb. 2015 to Mar. 2016 were included in the study. They were randomly divided into two groups. The 23 patients operated with the 3D system were compared with 23 patients operated with the 2D system by perioperative data.ResultsThere were no significant differences in age, sex, pathological type, tumor differentiation, TNM staging, and surgical procedures (P > 0.05). The average operating time of 3D laparoscopic surgery group (172.2 ± 27.5 min) was shorter than that of 2D group (192.6 ± 22.3) (P < 0.05); the rate of transfer to laparotomy is lower in 2D group (72.7%) than in 3D group (86.4%), but they have no significant difference; and the intraoperative blood loss (247.0 ± 173.6 ml vs 282.6 ± 195.6 ml), postoperative passage of flatus (2.8 ± 0.8 days vs 3.1 ± 1.0 days), and indwelling catheter time (5.6 ± 1.9 days vs 6.3 ± 2.0 days) in 3D group and 2D group (P > 0.05) were not significantly different. There were no differences in other complications between the two groups. No significantly different recrudescence and death rates were found between the two groups (P > 0.05).ConclusionThe 3D laparoscopy shortens the operation time of rectum cancer. 3D laparoscopic surgery is more efficient in treatment of rectal cancer than 2D laparoscopy and is worth of being generalized.

The gut microbiota plays an important role in cancer development and immunotherapy. Bacterial toxins have enormous antitumor potential due to their cytotoxicity and ability to activate the immune system. Using 16S rRNA gene sequencing, we compared the gut microbiota composition of fecal samples from healthy individuals and patients with colorectal cancer (CRC) and observed that the genus Bacillus was common in the healthy donors but was absent in the CRC patients. Further, we isolated a novel Bacillus toyonensis BV-17 from the fecal samples of the healthy individuals. Our results showed that the supernatant of the Bacillus toyonensis BV-17 cultures could quickly kill various tumor cell lines within minutes in vitro, by causing cell membrane disruption, blebbing, and leakage of cytoplasmic content. Fast protein liquid chromatography (FPLC) and mass spectrometry analysis identified hemolysin BL (HBL) as the effector molecule, which exhibits a different cytotoxicity mechanism compared to previous studies. Intra-tumor injection of low dose HBL inhibited the growth of both treated and untreated tumors in mice. The outcomes of this pioneer study suggest that HBL exhibits antitumor activity and is a potential chemotherapeutic agent that could be engineered to target only tumor cells in future.

ObjectiveChallenges remain in current practices of colorectal cancer (CRC) screening, such as low compliance, low specificities and expensive cost. This study aimed to identify high-risk groups for CRC from the general population using regular health examination data.MethodsThe study population consist of more than 7,000 CRC cases and more than 140,000 controls. Using regular health examination data, a model detecting CRC cases was derived by the classification and regression trees (CART) algorithm. Receiver operating characteristic (ROC) curve was applied to evaluate the performance of models. The robustness and generalization of the CART model were validated by independent datasets. In addition, the effectiveness of CART-based screening was compared with stool-based screening.ResultsAfter data quality control, 4,647 CRC cases and 133,898 controls free of colorectal neoplasms were used for downstream analysis. The final CART model based on four biomarkers (age, albumin, hematocrit and percent lymphocytes) was constructed. In the test set, the area under ROC curve (AUC) of the CART model was 0.88 [95% confidence interval (95% CI), 0.87−0.90] for detecting CRC. At the cutoff yielding 99.0% specificity, this model’s sensitivity was 62.2% (95% CI, 58.1%−66.2%), thereby achieving a 63-fold enrichment of CRC cases. We validated the robustness of the method across subsets of test set with diverse CRC incidences, aging rates, genders ratio, distributions of tumor stages and locations, and data sources. Importantly, CART-based screening had the higher positive predictive value (1.6%) than fecal immunochemical test (0.3%).ConclusionsAs an alternative approach for the early detection of CRC, this study provides a low-cost method using regular health examination data to identify high-risk individuals for CRC for further examinations. The approach can promote early detection of CRC especially in developing countries such as China, where annual health examination is popular but regular CRC-specific screening is rare.

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Background Preoperative neoadjuvant chemoradiation (nCRT) has been the standard treatment for locally advanced rectal cancer. Serum biomarkers to stratify patients with respect to prognosis and response to nCRT are needed due to the diverse response to the therapy. Methods Thirteen paired pre- and post-nCRT sera from rectal cancer patients were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) method. Twenty-five proteins were selected for validation by parallel reaction monitoring (PRM) in ninety-one patients. Results Totally, 310 proteins were identified and quantified in sera samples. Reactome pathway analysis showed that the immune activation-related pathways were enriched in response to nCRT. Twenty-five proteins were selected for further validation. PRM result showed that the level of PZP was higher in pathological complete response (pCR) patients than non-pCR patients. The Random Forest algorithm identified a prediction model composed of 10 protein markers, which allowed discrimination between pCR patients and non-pCR patients (area under the curve (AUC) = 0.886 on testing set). Higher HEP2 and GELS or lower S10A8 in baseline sera were associated with better prognosis. Higher APOA1 in post nCRT sera was associated with better disease-free survival (DFS). Conclusions We identified and confirmed a 10-protein panel for nCRT response prediction and four potential biomarkers HEP2, GELS, S10A8 and APOA1 for prognosis of rectal cancer based on iTRAQ-based comparative proteomics screening and PRM-based targeted proteomic validation.

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