Prognostic value of oxidative stress-related genes in colorectal cancer and its correlation with tumor immunity.

Oxidative stress (OS) plays an essential role in chronic diseases such as colorectal cancer (CRC). In this study, we aimed to explore the relation between oxidative stress-related genes and CRC prognosis and their involvement in the immune microenvironment. Totally 101 OS-related genes were selected from the MsigDB database. Then, univariate Cox regression was used to explore the prognostic value of the selected genes correlated with the CRC patient survival in the TCGA database. A total of 9 prognostic OS-related genes in CRC were identified. Based on consensus clustering, CRC patients were then categorized into two molecular subtypes. A prognostic risk model containing 8 genes was established using Lasso regression, and CRC patients were divided into high or low-risk groups based on the median risk scores. The predictive value of the 8 genes in CRC prognosis was validated using ROC curves, which indicate that CTNNB1, STK25, RNF112, SFPQ, MMP3, and NOL3 were promising prognostic biomarkers in CRC. Furthermore, the immune cell infiltration levels in different risk groups or CRC subtypes were analyzed. We found that the high-risk or C1 subtype had immunosuppressive microenvironment, which might explain the unfavorable prognosis in the two groups of CRC patients. Additionally, functional experiments were conducted to investigate the effects of OS-related genes on CRC cell proliferation, stemness, and apoptosis. We found that CTNNB1, HSPB1, MMP3, and NOL3 were upregulated in CRC tissues and cells. Knockdown of CTNNB1, HSPB1, MMP3, and NOL3 significantly suppressed CRC cell proliferation, stemness and facilitated CRC cell apoptosis. In conclusion, we established prognostic CRC subtypes and an eight-gene risk model, which may provide novel prognostic indicators and benefit the design of individualized therapeutic strategies for CRC patients.

Mesenchymal Stem Cell-Derived Exosomes are Effective for Radiation Enteritis and Essential for the Proliferation and Differentiation of Lgr5+ Intestinal Epithelial Stem Cells by Regulating Mir-195/Akt/ß-Catenin Pathway.

BACKGROUND: Radiation enteritis (RE) is a common complication of abdominal or pelvic radiotherapy, which when severe, could be life-threatening. Currently, there are no effective treatments. Studies have shown that mesenchymal stem cells (MSCs)-derived exosomes (MSC-exos) exhibit promising therapeutic effects in inflammatory diseases. However, the specific role of MSC-exos in RE and the regulatory mechanisms remain elusive. METHODS: In vivo assay was carried out by injecting MSC-exos into the total abdominal irradiation (TAI)-induced RE mouse model. For in vitro assay, Lgr5-positive intestinal epithelial stem cells (Lgr5+ IESC) were extracted from mice, followed by irradiation along with MSC-exos treatment. HE staining was performed to measure histopathological changes. mRNA expression of inflammatory factors TNF-α and IL-6 and stem cell markers LGR5, and OCT4 were quantified by RT-qPCR. EdU and TUNEL staining was performed to estimate cell proliferation and apoptosis. MiR-195 expression in TAI mice and radiation-induced Lgr5+ IESC was tested. RESULTS: We found that the injection of MSC-exos inhibited inflammatory reaction, increased stem cell marker expression, and maintained intestinal epithelial integrity in TAI mice. Furthermore, MSC-exos treatment increased the proliferation and simultaneously suppressed apoptosis in radiation-stimulated Lgr5+ IESC. MiR-195 expression increased by radiation exposure was decreased by MSC-exos therapy. MiR-195 overexpression facilitated the progress of RE by counteracting the effect of MSC-exos. Mechanistically, the Akt and Wnt/ß-catenin pathways inhibited by MSC-exos were activated by miR-195 upregulation. CONCLUSION: MSC-Exos are effective in treating RE and are essential for the proliferation and differentiation of Lgr5+ IESCs. Moreover, MSC-exos mediates its function by regulating miR-195 Akt ß-catenin pathways.

Efficacy of robot-assisted vs. laparoscopy surgery in the treatment of colorectal cancer: A systematic review and meta-analysis.

PURPOSE: To compare the efficacy of robot-assisted colorectal surgery (RACS) vs. laparoscopic-assisted colorectal surgery (LACS) in the treatment of colorectal cancer (CRC). METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) reporting on RACS and LACS in CRC patients published up to January 4, 2022. The outcomes included operative time, length of stay, conversion, circumferential resection margin positivity (CRM+), and complications. RESULTS: Six RCTs (412 participants with RACS and 420 with LACS) were included. The pooled results showed shorter operative time (WMD=44.28, 95%CI: 9.36, 79.19, P = 0.013; PQ<0.001) and lower costs in RACS than in LACS (WMD=1546.15, 95%CI: 761.51, 2330.78, P<0.001; PQ=0.208), while no differences were observed for the length of stay (WMD=-0.31, 95%CI: -1.13,0.51, P = 0.456; I2=0.0%, PQ=0.990), blood loss (WMD=-33.72, 95%CI: -205.06, 137.62, P = 0.700; I2=89.0%, PQ=0.003), the number of harvested lymph nodes (WMD=1.38, 95%CI: -0.09, 2.85, P = 0.066; I2=0.0%, PQ=0.645), the time of first flatus (WMD=0.20, 95%CI: -0.20, 0.61, P = 0.328; I2=0.0%, PQ=0.337), rates of conversion to open surgery (RR=0.62, 95%CI: 0.38,1.01, P = 0.053; I2=0.0%, PQ=0.459), complication rates (RR=1.11, 95%CI: 0.83,1.49, P = 0.466; I2=0.0%, PQ=0.948), and CRM+ rates (RR=1.02, 95%CI: 0.66,1.58, P = 0.938; I2=0.0%, PQ=0.408). No publication bias was detected. The sensitivity analyses showed that the results for the operative time were robust. CONCLUSIONS: Patients with CRC who underwent RACS and LACS had a similar length of stay, blood loss, the time of first flatus, rates of conversion to open surgery, the number of harvested lymph nodes, complication rates, and CRM+ rates; however, RACS led to longer surgeries and higher costs than LACS.

Targeting AURKA by microRNA-490-3p suppresses gastric cancer cell growth.

OBJECTIVE: To illustrate the molecular mechanism of microRNA-490-3p regulating gastric cancer (GC) cells by targeting AURKA. METHODS: Genes with significantly different expression in GC and normal tissue in TCGA-STAD dataset were analyzed by bioinformatics. Expression levels of genes and proteins in GC cells were measured by qRT-PCR and western blot. The interaction between microRNA-490-3p and AURKA was verified by dual luciferase assay. Proliferation, migration, invasion and apoptosis of GC cells were evaluated through a set of cell function assays. RESULTS: MicroRNA-490-3p was significantly less expressed in GC, while AURKA was significantly highly expressed. Dual luciferase reporter gene assay proved that microRNA-490-3p targeted AURKA. Up-regulation of microRNA-490-3p restrained proliferation, migration, invasion and stimulated apoptosis of GC cells, which was attenuated by overexpression of AURKA. CONCLUSIONS: MicroRNA-490-3p was likely to restrain the development of GC cells by inhibiting AURKA, and it may be an underlying target for GC treatment.

Up-regulation of Tim-3 is associated with poor prognosis of patients with colon cancer.

Tim-3 (T cell immunoglobulin and mucin domain 3), belonging to the member of the novel Tim family, has been confirmed that it plays a critical negative role in regulating the immune responses against viral infection and carcinoma. Recently, it has also been reported that the over-expression of Tim-3 is associated with poor prognosis in solid tumors. However, the role of Tim-3 in colorectal cancer remains largely unknown. In the current study, we aim to investigate the expression of Tim-3 in colorectal carcinoma and discuss the relationship between Tim-3 expression and colon cancer prognosis, thus speculating the possible role of Tim-3 in colon cancer progression. Colon cancer tissues and paired normal tissue were obtained from 201 patients with colon cancer for preparation of tissue microarray. Tim-3 expression was evaluated by immunohistochemical staining. The Tim-3 expression level was evaluated by q-RT-PCR, western blot and immunocytochemistry in four colon cancer cell lines (HT-29, HCT116, LoVo, SW620). Tim-3 was expressed in 92.5% tumor tissue samples and 86.5% corresponding normal tissue samples. Expression of Tim-3 was significantly higher in tumor tissues than in normal tissues (P < 0.0001). Tim-3 expression in colon cancer tissues is in correlation with colon cancer lymphatic metastasis and TNM (P < 0.0001). Multivariate analysis demonstrated that Tim-3 expression could be a potential independent prognostic factor for colon cancer patients (P < 0.0001). Kaplan-Meier survival analysis result showed that patients with higher Tim-3 expression had a significantly shorter survival time than those with lower Tim-3 expression patients. Our results indicated that Tim-3 might participate in the tumorgenesis of colon cancer and Tim-3 expression might be a potential independent prognostic factor for patients with colorectal cancer.