A bioinformatics framework to identify the biomarkers and potential drugs for the treatment of colorectal cancer.

Colorectal cancer (CRC), a common malignant tumor, is one of the main causes of death in cancer patients in the world. Therefore, it is critical to understand the molecular mechanism of CRC and identify its diagnostic and prognostic biomarkers. The purpose of this study is to reveal the genes involved in the development of CRC and to predict drug candidates that may help treat CRC through bioinformatics analyses. Two independent CRC gene expression datasets including The Cancer Genome Atlas (TCGA) database and GSE104836 were used in this study. Differentially expressed genes (DEGs) were analyzed separately on the two datasets, and intersected for further analyses. 249 drug candidates for CRC were identified according to the intersected DEGs and the Crowd Extracted Expression of Differential Signatures (CREEDS) database. In addition, hub genes were analyzed using Cytoscape according to the DEGs, and survival analysis results showed that one of the hub genes, TIMP1 was related to the prognosis of CRC patients. Thus, we further focused on drugs that could reverse the expression level of TIMP1. Eight potential drugs with documentary evidence and two new drugs that could reverse the expression of TIMP1 were found among the 249 drugs. In conclusion, we successfully identified potential biomarkers for CRC and achieved drug repurposing using bioinformatics methods. Further exploration is needed to understand the molecular mechanisms of these identified genes and drugs/small molecules in the occurrence, development and treatment of CRC.

Ultrasound and laser-promoted dual-gas nano-generator for combined photothermal and immune tumor therapy.

The combination of photothermal therapy (PTT) and immune tumor therapy has emerged as a promising avenue for cancer treatment. However, the insufficient immune response caused by inefficient immunogenic cell death (ICD) inducers and thermal resistance, immunosuppression, and immune escape resulting from the hypoxic microenvironment of solid tumors severely limit its efficacy. Herein, we report an ultrasound and laser-promoted dual-gas nano-generator (calcium carbonate-polydopamine-manganese oxide nanoparticles, CPM NPs) for enhanced photothermal/immune tumor therapy through reprogramming tumor hypoxic microenvironment. In this system, CPM NPs undergo reactive decomposition in a moderately acidic tumor, resulting in the generation of calcium, manganese ions, carbon dioxide (CO2), and oxygen (O2). Calcium and manganese ions act as adjuvants that trigger an immune response. The cancer cell membrane rupture caused by sudden burst of bubbles (CO2 and O2) under ultrasound stimulation and the photothermal properties of PDA also contributed to the ICD effect. The generation of O2 alleviates tumor hypoxia and thus reduces hypoxia-induced heat resistance and immunosuppressive effects, thereby improving the therapeutic efficacy of combination PTT and immune therapy. The present study provides a novel approach for the fabrication of a safe and effective tumor treatment platform for future clinical applications.

Long noncoding RNA SNHG6 functions as a competing endogenous RNA by sponging miR-181a-5p to regulate E2F5 expression in colorectal cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been identified as a novel class of regulators implicated in diverse biological processes in human cancers. Currently, evidence have shown that SNHG6, a cancer-associated lncRNA, exerts critical functions in gastric cancer and hepatocellular carcinoma; however, its role in colorectal cancer (CRC) remains unclear. METHODS: The expression of SNHG6 was determined by quantitative real-time PCR in CRC tissues and cells. SNHG6 was downregulated by using RNAi technology. Cell proliferation was examined by MTT and clone formation assays. Cell migration and invasion were determined by wound healing and transwell assays. Fluorescence in situ hybridization assays were performed to examine subcellular localization of SNHG6 in CRC cells. Fluorescence reporter and Western blot assays were used to explore the potential mechanisms of SNHG6 in CRC progression. RESULTS: In this study, we found that SNHG6 was significantly upregulated in CRC tissues and cell lines, compared with normal tissues and normal colorectal epithelial cell line NCM460, respectively. High expression of SNHG6 was positively correlated with tumor size, advanced TNM stage, and distant metastasis. Survival analyses revealed that SHNG6 was significantly associated with poor clinical outcomes and could serve as an independent prognostic factor. Loss-of-function studies demonstrated that SNHG6 knockdown inhibited CRC cell proliferation, induced G0/G1 arrest, promoted apoptosis, suppressed CRC cell migration and invasion, and restrained tumor growth. Mechanistic investigations showed that SNHG6 acted as a competing endogenous RNA for miR-181a-5p and attenuated the inhibitory effect of miR-181a-5p on E2F5. CONCLUSION: Taken together, these results demonstrated that SNHG6 plays a crucial role in CRC progression via miR-181a-5p/E2F5 axis. Therefore, SNHG6 may serve as a prognostic and therapeutic biomarker in CRC.

Expression levels of miR-205 and miR-506 in colon cancer tissues and their relationships with clinicopathological features.

The study intended to investigate the expression levels of micro ribonucleic acid (miR)-205 and miR-506 in colon cancer tissues and their relationships with clinicopathological features. The expression levels of miR-205 and miR-506 in colon cancer tissues and para-carcinoma normal colonic mucosa tissues were detected via fluorescence reverse transcription quantitative polymerase chain reaction (RT-qPCR), and the expression levels of the two miRNAs in plasma of colon cancer patients and healthy control population were also detected. Moreover, the relationships of the two miRNAs with clinicopathological features of patients with colon cancer were analyzed. The expression levels of the two miRNAs in colon cancer tissues were higher than those in para-carcinoma normal colonic mucosa tissues, and also significantly higher in plasma of the colon cancer patients than those in the healthy control population. The differences were statistically significant (P<0.05). The expression level of miR-205 was associated with tumor-node-metastasis (TNM) staging and lymph node metastasis, while the expression level of miR-506 was associated with lymph node metastasis. The differences were statistically significant (P<0.05). The expression levels of miR-205 in the colon cancer tissues and plasma in patients had no significant correlation (r=0.467, P=0.081). There was a positive correlation between the expression levels of miR-506 in the colon cancer tissues and plasma in patients (r=0.599, P=0.038). The expression levels of miR-205 and miR-506 are upregulated in the colon cancer patients, both of which may be closely related to the occurrence and development of colon cancer, and may become potential tumor markers as well as relevant therapeutic targets.

[Effect of continuous negative pressure drainage with intermittent irrigation on surgical site infection after laparoscopic extralevator abdominoperineal excison].

OBJECTIVE: To explore the effect of continuous negative pressure drainage with intermittent irrigation on surgical site infection (SSI) after laparoscopic extralevator abdominoperineal excison (ELAPE). METHODS: Clinical data of 28 rectal cancer patients who underwent continuous negative pressure drainage with intermittent irrigation following laparoscopic ELAPE (negative irrigation group) at our department from March 2016 to August 2017 were analyzed retrospectively. At the same time, 32 rectal cancer patients who underwent laparoscopic ELAPE and simple presacral drainage from January 2014 to February 2016 were included as controls (simple drainage group). Self-made double cannula: one silicon rubber drainage tube was used; 3 side holes were cut at the front end with 1-2 cm interval; tube was ranked intermittently and oppositely; a small hole was cut in the middle of rear; the infusion tube was placed through the small hole to the front side of the drainage tube (to rinse when the drainage was turbid). The placement and use of self-made double cannula: it was placed in the presacral space and was drawn from the medial to the sciatic tubercle, then was connected to drainage bag for 24 hours; when no blood was observed, the drainage tube was connected to negative pressure drainage ball, keeping negative pressure status. The development of SSI within 30 days postoperatively and other perioperative parameters were compared between the two groups. RESULTS: There were no statistically significant differences in baseline data between two groups (all P>0.05). Incidence of SSI in negative irrigation group was significantly lower than that in simple drainage group [14.3% (4/28) vs. 43.8% (14/32), χ2=6.173, P=0.013]. Additionally, a shorter postoperative hospital stay was observed in negative irrigation group [(9.8±1.5) days vs. (11.4±2.6) days, t=2.918, P=0.005]. Besides, other perioperative parameters, including operative time, intraoperative blood loss, time to removal of drainage tube, etc were not significantly different between two groups (all P>0.05). After adjusting to confounders, multivariate analysis showed that negative pressure drainage was an independent protective factor for SSI following laparoscopic ELAPE (OR=0.214, 95%CI:0.060-0.762, P=0.002). CONCLUSION: Continuous negative pressure drainage with intermittent irrigation can effectively decrease the incidence of SSI following laparoscopic ELAPE, and is safe and simple.

[A multi-modal image registration method for use in thermotherapy of tumor].

In the interactive image-guided thermotherapy, we need the real time image and location of the target tumor. But the current mono-modal imaging technique can not do it. We present a method to register a preoperative 3D MRI volume to a set of intra-operative ultrasound images for the target localization of the liver tumor in the thermotherapy. The registration method is a genetic algorithm based on the features such as liver surface vessels and liver surface.