Objective To investigate the relationship between preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) score, and clinicopathologic features of colon cancer, and to analyze the predictive value of HALP score for postoperative liver metastasis. Methods The clinical data of 163 patients with colon cancer admitted to the 909th Hospital of Joint Logistic Support Force (Dongnan Hospital of Xiamen University) from January 2018 to December 2019 were retrospectively analyzed. According to the occurrence of postoperative liver metastasis, the patients were divided into metastatic group (n=35) and non-metastatic group (n=128). The correlation between preoperative HAPL score and clinicopathologic features of colon cancer was analyzed. The predictive value of HALP score for postoperative liver metastasis of colon cancer was analyzed by using receiver operating characteristic (ROC) curve. The risk factors of liver metastasis after colon cancer surgery were analyzed by using univariate and multivariate logistic analysis. Kaplan-Meier risk curve was drawn, and log-rank test was used to analyze the predictive value of different HALP score for postoperative liver metastasis. Results HALP score were decreased in patients with maximum tumor diameter ≥5 cm, preoperative carcinoembryonic antigen (CEA) ≥5 μg/L, serous membrane and extrasserous infiltration, lymph node metastasis and vascular invasion, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that HALP score [OR=1.467, 95%CI (1.253, 1.718), P<0.001], maximum tumor diameter [OR=3.476, 95%CI (1.475, 5.358), P=0.013], preoperative CEA level [OR= 6.197, 95%CI (2.436, 6.248), P=0.005], and lymph node metastasis [OR=2.593, 95%CI (1.667, 6.759) , P=0.003] were risk factors for postoperative liver metastasis of colon cancer. ROC curve analysis showed that the area under the curve of HALP score for predicting liver metastasis after colon cancer surgery was 0.908 (0.841, 0.974), the maximum value of the Youden index was 0.738, the optimal cut-off value of the HALP score was 35.5, the sensitivity was 0.852, the specificity was 0.886. Kaplan-Meier risk curve showed that the risk of early postoperative liver metastasis in the low HALP score group was higher than that in the high HALP score group (χ2=8.126, P=0.004). Conclusion Low HALP score in patients with colon cancer is associated with adverse prognosisi related pathological features, and is an influential factor for postoperative liver metastasis of colon cancer, and has predictive value for patients with postoperative liver metastasis of colon cancer.
ObjectiveTo compare the short- and long-term effects of emergency surgery (ES) and self-expanding metal stent (SEMS) in treatment of malignant left-sided colonic obstruction.MethodsThe patients with malignant left-sided colonic obstruction who met the inclusion and exclusion criteria in the Third Affiliated Hospital of Soochow University from October 2010 to October 2020 were retrospectively collected and divided into ES group (n=43) and SEMS group (n=22). The baseline data, surgical data, postoperative data, and prognosis (overall survival and relapse free survival) were compared, and the risk factors of tumor recurrence after surgery were further analyzed by Cox proportional hazards regression model. ResultsIn this study, 65 cases of malignant left-sided colonic obstruction were included, including 43 cases in the ES group and 22 cases in the SEMS group. There were no statistical differences in the baseline data of the two groups (P>0.05). There were no significant differences in the incidence of postoperative complications [13.6% (3/22) vs. 23.3% (10/43), P=0.555], recurrence rate [40.9% (9/22) vs. 37.2% (16/43), P=0.772], and rate of receiving postoperative chemotherapy [68.2% (15/22) vs. 48.8% (21/43), P=0.138] between the SEMS group and ES group. Compared with the ES group, although the median hospitalization time was longer (20 d vs. 12 d, P=0.001), and the median hospitalization cost was higher (65 033 yuan vs. 40 045 yuan, P=0.001), the stoma rate of the SEMS group was lower [36.4% (8/22) vs. 88.4% (38/43), P=0.001], and the minimally invasive (laparoscopic) rate was higher [36.4% (8/22) vs. 7.0% (3/43), P=0.008]. There were no significant differences in the 4-year cumulative overall survival (46.9% vs. 48.4%, P=0.333) and 4-year cumulative relapse free survival (36.2% vs. 44.8%, P=0.724) between the SEMS group and ES group, but the overall survival of the SEMS group was better than that of the ES group for the patients with stage Ⅲ–Ⅳ (χ2=4.644, P=0.047). Multivariate analysis of Cox proportional hazards regression model showed that increased TNM stage increased the risk of postoperative tumor recurrence of patients with malignant left-sided colonic obstruction [HR=2.092, 95%CI (1.261, 3.469), P=0.004]. ConclusionsShort- and long-term effects of ES and SEMS in treatment of malignant left-sided colonic obstruction are equivalent. Although SEMS mode has a longer hospital stay and higher hospitalization costs, stoma rate is lower and laparoscopic surgery rate is higher. Overall survival of SEMS mode in treatment malignant left-sided colonic obstruction patients with stage Ⅲ–Ⅳ is better.
Objective To explore the influencing factors for pulmonary infection after radical resection of colon cancer. Methods A cohort study included 56 patients who underwent radical resection of colon cancer in People’s Hospital of Daye City from Oct. 2014 to Oct. 2016 were followed-up prospectively, to observe the occurrence of pulmonary infection, and collectting the related factors for pulmonary infection in addition. Results The clinical data of 53 patients were finalized and the clinical data of these patients were complete. Among them, 13 patients suffered from pulmonary infection after radical resection of colon cancer, and 40 patients had no obvious exacerbation and no complicated pulmonary infection. Results of logistic regression showed that, value of forced expiratory volume in1 second/forced vital capacity (OR=1.174, P=0.033), operative time (OR=1.638, P=0.012), levels of postoperative copeptin (OR=1.328, P=0.032), and procalcitonin (OR=1.465, P=0.042) were risk factors for pulmonary infection after radical resection of colon cancer. Receiver operating characteristic curve (ROC) showed that, operative time was 6.207-hour, postoperative copeptin level was 10.420 pmol/L, and the postoperative procalcitonin level was 3.676 ng/mL, which had the best predictive effect on predicting pulmonary infection after radical resection of colon cancer. Conclusions Value of forced expiratory volume in 1 second/forced vital capacity, operative time, levels of copeptin and procalcitonin after operation are the independent influencing factors for pulmonary infection after radical resection of colon cancer, and it has best prognostic outcome when the operative time is 6.207-hour, postoperative copeptin level is 10.420 pmol/L, and the postoperative procalcitonin level is 3.676 ng/mL.
Objective To explore the relationship between Epstein-Barr virus (EBV) infection with serum human kissin-1 (KISS-1) and matrix metalloproteinase 2 (MMP2) levels and prognosis in patients with colon cancer. Methods A total of 86 colon cancer patients who were hospitalized in our hospital from April 2015 to April 2016 were selected as the colon cancer group; in the same period, 84 cases of physical examination person in our hospital were selected as the control group. Real-time fluorescent quantitative PCR (qRT-PCR) was used to test colon cancer patients for EBV DNA, and divided the patients into EBV DNA negative group and EBV DNA positive group according to the test results. Enzyme-linked immunosorbent (ELISA) method was used to detect serum KISS-1 and MMP2 levels. Pearson method was used to analyze the correlation between serum KISS-1 and MMP2 levels in patients with colon cancer infected with EBV. The survival curve was drawn by Kaplan-Meier method, and the relationship between EBV infection and prognosis of colon cancer patients was analyzed by log-rank test. Multivariate Cox regression analysis were used to analyze the factors affecting the prognosis of colon cancer patients. Results Compared with the control group, the positive rate of EBV DNA in the colon cancer group was higher (χ2=21.854, P<0.001). The EBV DNA positive rate of patients with lymph node metastasis, TNM stage Ⅲ–Ⅳ, tumor low differentiation and tumor infiltration T3–T4 was higher than those without lymph node metastasis, TNM stage Ⅰ–Ⅱ, tumor high/medium differentiation and tumor infiltration T1–T2 (P<0.05). Compared with the EBV DNA negative group, the serum KISS-1 level of the EBV DNA positive group decreased, and the MMP2 level increased (P<0.001). There was a negative correlation between serum KISS-1 and MMP2 levels in colon cancer patients with EBV infection (r=–0.510, P<0.001). The 5-year survival rates of colon cancer patients in the EBV DNA-negative group and the EBV DNA-positive group were 52.94% (27/51) and 14.29% (5/35), respectively, the difference between the two groups was statistically significant (χ2=13.274, P<0.001). EBV infection, MMP2 high expression, and lymph node metastasis were independent risk factors affecting the prognosis of colon cancer patients (P<0.05), and KISS-1 low expression was a protective factor affecting the prognosis of colon cancer patients (P<0.05). Conclusions EBV infection is closely related to the progression and prognosis of colon cancer. The down-regulation of KISS-1 and the up-regulation of MMP2 may be related to EBV infection.
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.
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.
ObjectiveTo investigate the regulatory role of DAB2IP in proliferation effect of colon cancer cells by salinomycin. MethodsCell counting kit 8 (CCK8) assay was used to detect median inhibitory concentration (IC50) of salinomycin on HT29 and SW480 cells. Colon cancer cells with stable knock-down of DAB2IP (HT29-shDAB2IP) and control cells (HT29-shcon) were constructed by lentivirus plasmid. And colon cancer cells with stable over-expression of DAB2IP (SW480-DAB2IP) and control cells (SW480-con) were constructed using pCI plasmid. The proliferation effect of salinomycin on stable knock-down or over-expression of DAB2IP by CCK8 assay in the colon cancer cell was identified. The colon cancer stem cells makers CD44, CD24, and CD133 were investigated using real-time PCR. ResultsThe salinomycin had obvious inhibitory effects on the proliferations of HT29 and SW480 cells, the IC50 value was 20.0 μmol/L and 10.0 μmol/L, respectively. The stable knock-down of DAB2IP could significantly enhance the inhibitory effect of salinomycin on the proliferation in HT29 cells (P<0.05) and stable over-expression of DAB2IP could significantly decrease the inhibitory effect of salinomycin on the proliferation in SW480 cells (P<0.05). Further the result of real-time PCR detection showed that the expressions of cancer stem cells markers CD44, D24, and CD133 were significantly increased after stable knock-down of DAB2IP in the HT29 cells (P<0.05), while the expressions were significantly decreased after stable over-expression of DAB2IP in the SW480 cells (P<0.05). ConclusionsFrom initial results of this study, salinomycin could suppress proliferation of colon cancer cells. DAB2IP might weaken proliferative inhibitory effect of salinomycin by inhibiting expressions of cancer cells stem in colon cancer cells.
ObjectiveTo evaluate safety and effectiveness of stent placement and emergency surgery in treatment of proximal colon cancer obstruction.MethodsThe PubMed, Embase, Cochrane Library, ClinicalTrials, CNKI, CBM, Wanfang Data, etc. were searched comprehensively. The literatures of Chinese and English randomized controlled trial and retrospective comparative study of stent placement and emergency surgery for the proximal colon cancer obstruction were retrieved. The RevMan 5.3 and Stata 12.0 softwares were used. The meta-analysis was made on the safety and effectiveness of these two treatments.ResultsA total of 9 literatures involving 636 patients were included, all of them were the retrospective studies, 4 of them only reported the clinical success rate and technical success rate. The technical success rate of stent placement was 0.94 [95% CI (0.91, 0.96)]. The clinical success rate was 0.90 [95% CI (0.87, 0.93)]. Compared with the emergency surgery group, the total complication rate and the temporary stoma rate were lower [OR=0.32, 95% CI (0.11, 0.94), P=0.04; OR=0.18, 95% CI (0.05, 0.65), P=0.009] and the hospital stay was shorter [MD=–2.97, 95% CI (–4.52, –1.41), P=0.000 2] in the stent placement group. The perioperative mortality rate, laparoscopic surgery rate, 5-year disease-free survival rate, and 5-year overall survival rate had no significant differences between these two groups (P>0.05).ConclusionCompared with emergency surgery, endoscopic stent placement for treatment of proximal colon cancer obstruction has a lower incidence of complications, temporary colostomy rate, shorter hospital stay, and it has no significant differences in mortality, laparoscopic surgery rate, and survival rate.
ObjectiveTo develop an immune-related genes (IRGs) based prognostic signature and evaluate the value in predicting prognosis in patients with colon cancer.MethodsGene chip data sets of 452 colon cancer patients were collected from the TCGA database, and 2 498 IRGs data sets were obtained from the ImmPort database. After taking the intersection, univariate and multivariate Cox proportional hazards regression analysis were used to screen and construct the IRGs gene model. To evaluate the prognostic value of genetic models, Cox proportional hazards regression was used to analyze the correlation between IRGs model/clinicopathological features with prognosis of colon cancer. The relationship between risk score and immune cell infiltration was analyzed too.ResultsA total of 206 differentially expressed IRGs were identified in colon cancer tissues, and 11 kinds of IRGs were identified by univariate and multivariate Cox proportional hazards regression analysis: solute carrier family 10 member 2 (SLC10A2), C-X-C motif chemokine ligand 5 (CXCL5), C-C motif chemokine ligand 28 (CCL28), immunoglobulin kappa variable 1D-42 (IGKV1D-42), chromogranin A (CHGA), endothelial cell specific molecule 1 (ESM1), gastrin releasing peptide (GRP), stanniocalcin 2 (STC2), urocortin (UCN), oxytocin receptor (OXTR) and immunoglobulin heavy constant gamma 1 (IGHG1). Colon cancer patients were divided into high risk group and low risk group according to the median value of risk value of IRGs risk markers. Patients in the high risk group had shorter overall survival (OS) than that in the low risk group (P<0.001). The area of the time-dependent ROC curve (AUC) was 0.754, suggesting that IRGs model had a good ability to predict the prognosis of colon cancer patients. The higher the risk value of IRGs, the later T stage of colon cancer (T3–T4), the more lymph node metastasis (N1–N2) and the later clinical stage of colon cancer (Ⅲ–Ⅳ), P<0.05. Except for neutrophils, the infiltration density of B cells, CD4+ T cells, CD8+ T cells, dendritic cells and macrophages were significantly increased with the increased of the risk value (P<0.05).ConclusionThe risk values of the 11 kinds of IRGs gene models screened in this study can be used to predict the prognosis of colon cancer patients, and can be used as biomarkers to evaluate the prognosis of colon cancer patients.
Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i.e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.