ObjectiveCombined with long non-coding RNA (lncRNA) to find a regression model that can be used to predict the survival rate of patients with colon cancer before operation.MethodsThe clinical information and gene expression information of patients with colon cancer were downloaded by using TCGA database. The differentially expressed lncRNAs in tumor and paracancerous tissues were screened out, and then combined with the clinical information of patients to construct Cox proportional hazard regression model.ResultsA total of 26 kinds of lncRNAs with statistical difference in gene expression between paracancerous tissues and tumor tissues were selected (P<0.05). Through repeated screening and comparison of prediction efficiency, the prediction model was finally selected, which was constructed by patients’ age, M stage, N stage, and three kinds of lncRNAs (ZFAS1, SNHG25, and SNHG7) gene expression level: age [HR=4.00, 95%CI: (1.48, 10.84), P=0.006], M stage [HR=3.96, 95%CI: (2.23, 7.04), P<0.001], N stage [HR=1.87, 95%CI: (1.24, 2.84), P=0.003], ZFAS1 gene expression level [HR=0.60, 95%CI: (0.41, 0.86), P=0.006], SNHG25 gene expression level [HR=0.85, 95%CI: (0.73, 1.00), P=0.045], and SNHG7 gene expression level [HR=2.32, 95%CI: (1.53, 3.52), P<0.001] were all independent risk factors for postoperative survival of patients with colon cancer. The area under the ROC curves for predicting 1, 3, and 5-year overall survival were 0.802, 0.828, and 0.771, respectiely, which had a good prediction ability.ConclusionThe predictive model constructed by the combination of ZFAS1, SNHG25, SNHG7 genes expression level with M stage, N stage, and age can better predict the overall survival rate of patients before operation, which can effectively guide clinical decision-making and choose the most suitable treatment method for patients.
Objective To investigate whether miRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colon cancer cells by inhibiting macroautophagy via the transforming growth factor (TGF)-β/Smad4 pathway. Methods miR-34a expression levels were detected in colon cancer tissues and colon cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Computational search, functional luciferase assay, and Western blotting method were used to demonstrate the downstream target of miR-34a in colon cancer cells. Cell viability was measured with cell counting kit-8. Apoptosis and macroautophagy of colon cancer cells were analyzed by flow cytometry and transmission electron microscopy, and expressions of Beclin1 and LC3Ⅱ protein were detected by Western blotting method. Results Expression of miR-34a was significantly reduced while expressions of TGF-β and Smad4 mRNA were increased in colon cancer patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased miR-34a expression levels and increased TGF-β and Smad4 expression levels in both parental cells and the OXA-resistant colon cancer cells. Activation of macroautophagy contributed to OXA resistance in colon cancer cells. Expression levels of Smad4 and miR-34a in colon cancer patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34a and increased drug resistance by activating macroautophagy in colon cancer cells. Conclusion miR-34a mediates OXA resistance of colon cancer by inhibiting autophagy via the TGF-β/Smad4 pathway.
ObjectiveTo investigate the feasibility and safety of the double cavity casing negative pressure drainage by inside and outside of the intestine in the primary resection and anastomosis of left colon cancer combined with acute obstruction. MethodsEighty-one cases of left colon cancer combined with acute obstruction who underwent surgeries in our hospital from January 2009 to December 2012 were collected prospectively, and were divided into one-stage surgery group (n=41) and control group (n=40). Cases of one-stage surgery group received double cavity casing negative pressure drainage by inside and outside of the intestine in the primary resection and anastomosis, and cases of control group underwent two-stage surgeries. Comparison of operation time, blood loss, time of anal exhaust after operation, hospital stay, hospital expense, and incidence of complication between the 2 groups was performed. ResultsThere were no significant difference in the operation time[(166±19) minutes vs. (173±23) minutes], blood loss[(253±42) mL vs. (273±50) mL], and time of anal exhaust after operation[(3.24±0.73) days vs. (3.50±0.95) days]beeween one-stage surgery group and control group, but hospital stay[(15.1±2.3) days vs. (23.1±4.1) days]and hospital expense[(3.70±0.68) ×105 yuan vs. (5.77±0.95) ×105 yuan]of one-stage surgery group were lower than those of control group (P<0.05). In addition, there were no significant difference in the incidences of wound infection[7.3% (3/41) vs. 10.0% (4/40)], intraabdominal infection[4.9% (2/41) vs. 10.0% (4/10)], pulmonary infection[12.2% (5/41) vs. 15.0% (6/40)], and anastomotic leakage[2.4% (1/41) vs. 5.0% (2/40)]beeween one-stage surgery group and control group (P>0.05). All of the cases were followed up for 1-36 months, and the median time were 22 months. There were no significant difference in the mortality[0 (0/41) vs. 2.5% (1/40)], recurrence rate[2.4% (1/41) vs. 5.0% (2/40)], and metastasis rate[7.3% (3/41) vs. 10.0% (4/40)]beeween one-stage surgery group and control group too (P>0.05). ConclusionIn the case of negative pressure drainage of double cavity casing, underwent decompression of the small bowel, and irrigation of colon, the primary resection and anastomosis of left colon cancer combined with acute obstruction was safe and feasible.
Objective To investigate the inhibition effect of silence of a disintegrin and metalloproteinase 17 (ADAM17) gene on proliferation and apoptosis of HT29 colon cancer cells and its possible mechanism. Methods HT29cells were divided into 3 groups: cells of interference group were transfected with recombinant lentivirus vector, cells of negative control group were transfected with negative recombinant lentivirus vector, and cells of blank control group were treated with PBS. The expression of ADAM17 mRNA was detected by real-time PCR, the expressions of ADAM17 protein, caspase3, protein kinase B (Akt), glycogen synthase kinase-3β (GSK3β), phospho-protein kinase B (P-Akt), phospho-glycogen synthase kinase-3β (P-GSK3β) protein were detected by Western blot method, the cell proliferation was detected by MTT assay, and the apoptosis rate was detected by Annexin V-FITC/PI cell death detection kit. Results Compared with the control group and the negative control group, the interference group was related to low expressions of ADAM17 mRNA and its protein, low optical density value at the same time point (24, 48, and 72 h), high apoptosis rate, high expression level of caspase3 protein, but low expression levels of P-Akt and P-GSK3β protein (P<0.05). Conclusion Silent ADAM17 gene could significantly induces apoptosis and inhibits the proliferation of HT29 cells, which maybe via inhibiting Akt/GSK3β signaling pathway.
Objective To investigate the role of long non-coding RNA metastasis-associated in colon cancer 1-antisense RNA （MACC1-AS1）in cisplatin resistant gastric cancer and its possible mechanism. Methods Human gastric cancer cell line BGC823 and cisplatin resistant gastric cancer cell line (BGC823/DDP) were selected as the research objects. BGC823/DDP cells were transfected and divided into negative control group (si-NC group, transfected with si-NC empty plasmid) and MACC1-AS1 gene silencing group (si-MACC1-AS1 group, transfected with si-MACC1-AS1 plasmid). The BGC823 cells were transfected and divided into positive control group (pcDNA-NC group, transfected with pcDNA-NC empty plasmid) and MACC1-AS1 gene overexpression group (pcDNA-MACC1-AS1 group, transfected with pcDNA-MACC1-AS1 plasmid). MTT was used to detect the inhibition and 50% inhibition concentration (IC50). Flow cytometry was used to detect apoptosis. Real-time fluorescence quantitative PCR was used to detect the mRNA expression levels of MACC1-AS1, B-lymphoma-2 gene (Bcl-2), Bcl-2 related X gene (Bax), mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), protein kinase B (AKT), and phosphorylated AKT (p-AKT). Western blot was used to detect the protein expression levels of Bax, Bcl-2, p-mTOR, mTOR, AKT, and p-AKT. Results The relative expression level of MACC1-AS1 mRNA in BGC823/DDP cells was higher than that in BGC823 gastric cancer cells (P<0.01). The relative expression level of MACC1-AS1 mRNA in the si-MACC1-AS1 group cells was lower than that in the si-NC group cells (P<0.01). The relative expression level of MACC1-AS1 mRNA in the pcDNA-MACC1-AS1 group cells was higher than that in the pcDNA-NC group cells (P<0.01). The cell growth inhibition rate and IC50 of the si-MACC1-AS1 group were higher than those of the si-NC group (P<0.01). The cell growth inhibition rate and IC50 of the pcDNA-MACC1-AS1 group were lower than those of the pcDNA-NC group (P<0.01). The mRNA and protein relative expression levels of Bcl-2, p-AKT/AKT and p-mTOR/mTOR in the pcDNA-MACC1-AS1 group were significantly higher than those in the pcDNA-NC group (P<0.01). The relative expression levels of Bax protein and mRNA in the pcDNA-MACC1-AS1 group were significantly lower than those in the pcDNA-NC group (P<0.01). The apoptosis rate of the pcDNA-MACC1-AS1 group was significantly lower than that of the pcDNA-NC group (P<0.01). The mRNA and protein relative expression levels of Bcl-2, p-AKT/AKT and p-mTOR/mTOR in the si-MACC1-AS1 group were significantly lower than those in the si-NC group (P<0.01). The relative expression levels of Bax protein and mRNA in the si-MACC1-AS1 group were significantly higher than those in the si-NC group (P<0.01). The apoptosis rate of the si-MACC1-AS1 group was significantly higher than that of the si-NC group (P<0.01). Conclusions MACC1-AS1 highly expresses in cisplatin resistant gastric cancer cells. Overexpression of MACC1-AS1 regulates AKT/mTOR pathway mediated apoptosis and enhances cisplatin resistance of gastric cancer cells.
Objective To evaluate the feasibility of sentinel lymph node (SLN) mapping after 99Tcm sulfur colloid (99Tcm-sc) and carbon nanoparticles injection in patients with colon cancer. Methods Forty patients with colon cancer underwent complete mesocolic excision between August 2015 and July 2016 at Qingdao Central Hospital were considered for prospective inclusion. Before resection, SLN mapping was performed with injection of 99Tcm-sc and carbon nanopar-ticles, then all dissected lymph nodes were detected by pathological examination. Results A total of 660 cases of lymph nodes were found in the 40 patients (average of 16.5 cases per patient). Of them, 88 nodes (average of 2.2 cases per patient) were identified as SLN in 36 of 40 patients, with a successful detection rate of 90.0% (36/40). The diagnostic accuracy, sensitivity, and false-negative rate were 87.5% (35/40), 96.2% (25/26), and 3.8% (1/26) respectively. Conclusion 99Tcm-sc and carbon nanoparticles suspension injection for mapping SLN is a feasiblely diagnostic method for predicting local lymph node metastasis in the patient with colon cancer.
ObjectiveTo investigate effect of Notch pathway regulating by inhibiting expression of forkhead box protein A1 (FOXA1) on proliferation and invasion of colon cancer SW480 cells. MethodsThe colon cancer tissues and their corresponding paracancerous tissues of 45 patients with colon cancer admitted to the First Affiliated Hospital of Henan University of Science and Technology from June 2019 to February 2021 were selected. The immunohistochemistry and real-time fluorescent quantitative PCR (qRT-PCR) methods were used to detect the expressions of FOXA1 protein and mRNA in the tissues, respectively. In addition, SW480 cells were divided into control group (untreated), shRNA-NC group (transfected with shRNA-NC), sh-FOXA1 group (transfected with sh-FOXA1), sh-FOXA1+sodium valproate group (Add 8 mmol/L Notch pathway activator sodium valproate after transfection with sh-FOXA1). Then the qRT-PCR, MTT, clone formation test, and Transwell methods were used to detect the expressions of FOXA1 mRNA, proliferation, clonogenic ability, invasion and migration of cells in each group. Western blot method was used to detect the proliferation (c-Myc, cyclinD1), invasion and migration [matrix metalloproteinase (MMP）9, MMP2], epithelial-mesenchymal transition (Vimentin, N-cadherin, E-cadherin) and Notch pathway (Notch-1, Hes-1) related protein expressions of cells in each group. Results① In the clinical cases, the expression levels of FOXA1 protein and mRNA in the colon cancer tissues were higher than those in the corresponding paracancerous tissues (protein: 0.085±0.028 vs. 0.034±0.010, t=11.036, P<0.001; mRNA: 1.62±0.34 vs. 1.00±0.09, t=11.671, P<0.001). ② In the cell experiment, compared with the control group and shRNA-NC group, the cell survival rate, and numbers of cloned cells, invasion and migrating cells were significantly reduced (P<0.05), correspondingly, the related proteins expression levels of c-Myc, cyclinD1, MMP9, MMP2, Vimentin, N-cadherin, Notch-1, Hes-1 were significantly reduced (P<0.05) and the protein expression level of E-cadherin was significantly increased (P<0.05) in the sh-FOXA1 group, which were reversed after adding the Notch pathway activator sodium valproate (P<0.05). ConclusionFOXA1 highly expresses in colon cancer tissues and colon cancer cells and it might promote the proliferation, invasion and migration of SW480 cells by activating the Notch pathway.
ObjectiveTo investigate the effects of overexpression of alpha/beta hydrolase domain-containing protein 5 (ABHD5) on the invasion and migration of human colon cancer cell line HCT116 and the pathway of adenosine monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR).MethodsThe expression of ABHD5 in colon cancer tissues and its relationship with clinicopathological features was analyzed by UALCAN database. HCT116 cells were cultured in vitro and transfected with ABHD5 recombinant plasmid, then they were divided into control group, negative transfection group and ABHD5 transfection group. Real time quantitative PCR (qRT-PCR) was used to detect the expression of ABHD5 mRNA in HCT116 cells. The proliferation of HCT116 cells was detected by CCK-8 method. Transwell assay was used to detect the invasion and migration of HCT116 cells. The expression of matrix metalloprotein 9 (MMP-9), E-cadherin, Snail, and AMPK/mTOR pathway proteins p-AMPK, AMPK, p-mTOR and mTOR were detected by Western blot.ResultsThe results of the UALCAN showed that compared with normal colon tissues, the expression of ABHD5 mRNA in colon cancer tissues was decreased (P<0.05), and which in the adenocarcinoma and the N1 stage was lower than that of the mucinous adenocarcinoma (P<0.05) and N0 stage (P<0.05), respectively. Compared with the control group and the negative transfection group, the expression of ABHD5 mRNA in the ABHD5 transfection group was increased (P<0.05), the proliferation inhibition rate of HCT116 cells in the ABHD5 transfection group was increased (P<0.05), the numbers of migration and invasion cells in the ABHD5 transfection group were decreased (P<0.05), the expressions of MMP-9, Snail, p-mTOR and mTOR were reduced, and the expressions of E-cadherin, p-AMPK and AMPK were increased (P<0.05).ConclusionsThe overexpression of ABHD5 can inhibit the invasion and migration of colon cancer HCT116 cells, activate AMPK, and inhibit the expression of mTOR. It suggests that ABHD5 may play a role in inhibiting colon cancer by affecting AMPK/mTOR pathway.
ObjectiveTo summarize the diagnosis and treatment of a primary gastric colon cancer, and to explore its safety and feasibility.MethodThe clinical data of a patient with gastric cancer and sigmoid colon cancer who admitted to The Affiliated Yantai Yuding Hospital of Qingdao University in October 2017 was analyzed.ResultsThe patient underwent laparoscopic radical gastrectomy plus π anastomosis and laparoscopic radical resection of colon cancer. The operation time was 330 min and the intraoperative blood loss was 120 mL. There were no complications such as stomach cramps and sputum after operation and he was successfully discharged on the 9th day after surgery. Postoperative pathological staging: gastric cancer (pT3N3M0, ⅢB) and sigmoid colon cancer (pT2N0M0, Ⅰ B).ConclusionsMultiple primary cancer of the simultaneous gastric colon should be diagnosed before operation. Laparoscopic minimally invasive treatment for gastric cancer with sigmoid colon cancer is safe and feasible, and can benefit patients.
ObjectiveTo assess the effect of chewing gum on the recovery of postoperative gastrointestinal function in patients with colorectal cancer. MethodsA comprehensive search for relevant randomised controlled trials (RCTs) was conducted in domestic and international databases such as PubMed, The Cochrane Library, Web of Science, Chinese Science and Technology Journal Full-text Database, Chinese Periodicals Full-text Database, Wanfang data, and other databases, with a timeframe up to September 2023. The literature was screened according to the inclusion and exclusion criteria. Simultaneously, the literature quality evaluation and data extraction were performed. The continuous variables were described using mean difference (95% confidence interval) and the binary variables were described using odds ratio (95% confidence interval). Test level was α=0.05. ResultsA total of 28 RCTs covering 2 523 postoperative colorectal cancer patients were included. The meta-analysis results showed that the postoperative chewing gum could shorten the time of the first flatus [–11.99 (–14.45, –9.53)], the first defecation [–18.79 (–23.58, –14.00)], the first bowel sounds [–6.35 (–6.64, –6.06)] or the first starvation [–5.20 (–10.11, –0.28)], and the hospital stay [–1.35 (–1.99, –0.70)], as well as could increase the serum gastrin level [23.70 (14.88, 32.53)]. Furthermore, it also could decrease the incidence of postoperative complications, such as nausea [0.66 (0.48, 0.91)], abdominal distension [0.48 (0.35, 0.67)], and intestinal obstruction [0.34 (0.20, 0.59)]. However, there was a non-significant effect on vomiting [0.81 (0.60, 1.09)] or time of the first oral intake [–0.67 (–1.99, 0.65)]. ConclusionsFrom the results of this meta-analysis, postoperative gum chewing aids to promote the recovery of gastrointestinal function and reduce the risk of postoperative complications in colorectal cancer patients. Although further studies are needed to verify the long-term effects and the feasibility of clinical application, the results of this study provide an important empirical support for the utilize of chewing gum in the management of postoperative gastrointestinal function.