ObjectiveTo systematically evaluate the effect of mucin 1 (MUC1) expression on the prognosis and clinicopathologic characteristics of patients with colorectal cancer.MethodsThe cohort studies on the relationship between MUC1 expression and the prognosis of colorectal cancer patients were retrieved from PubMed, Embase, Web of Science, Cochrane Library, CNKI, China Biology Medicine, WanFang, VIP, and other databases from the establishment of the database to December 2020. The two researchers screened the literatures according to the inclusion and exclusion criteria, extracted relevant data, and performed meta analysis using Stata 12.0 software.ResultsA total of 17 eligible studies comprising 2 516 patients with colorectal cancer were included. The results of meta-analysis showed that the overall survival (OS) of patients with high MUC1 expression was worse than that with low MUC1 expression [HR=1.51, 95%CI (1.33, 1.71), P<0.001], but not statistically significant with disease-free survival [HR=1.39, 95%CI (0.41, 4.68), P=0.565]. Subgroup analysis results showed the same results as the overall analysis regardless of analysis method (multivariate or survival curve), different ethnic groups (Asian or Caucasian), and different sample sizes (≥100 or <100). The results of clinicopathologic analysis showed that the high expression of MUC1 was correlated with lymph node metastasis, distant metastasis, depth of invasion, and TNM stage (P<0.05), but not correlated with gender, age, degree of tumor differentiation, and tumor location (P>0.05).ConclusionsHigh expression of MUC1 is closely associated with poor prognosis, lymph node metastasis, distant metastasis, tumor invasion depth, and TNM stage in patients with colorectal cancer, which is expected to be an important reference indicator for disease monitoring and prognosis judgment of colorectal cancer.
Objective To study the relationships between expressions of somatostatin receptor subtypes（SSTR1-SSTR5） and angiogenesis in colorectal cancer. Methods The expressions of SSTR1-SSTR5, VEGF, and CD34 in the paraffin sections of colorectal cancer tissues from 127 cases were detected by the standard streptavidin-peroxidase (SP) technique. CD34 was used as a marker to account microvessel density (MVD) in colorectal cancer tissues. The relationships between the expressions of SSTR1-SSTR5 and VEGF expression, or MVD were analyzed. Results The positive expression rate of SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 was 64.6% （82/127）, 36.2% （46/127）, 18.9% （24/127）, 18.9% （24/127）, and 38.6% （49/127） in colorectal cancer tissues, meanwhile, the positive expression rate of VEGF was 63.8% （81/127） and MVD was (34.67±16.62)/HP in colorectal cancer tissues. The positive expression rate of VEGF (47.8%， 22/46) and MVD 〔(29.00±15.32)/HP〕 in colorectal cancer tissues with SSTR2 positive expression were significantly lower than those in colorectal cancer tissues with SSTR2 negative expression 〔72.8%， 59/81； (37.90±16.56)/HP〕, Plt;0.05. There were no relationships between SSTR1, SSTR3, SSTR4, and SSTR5 expression and VEGF expression or MVD （Pgt;0.05）. Conclusion The positive expression of SSTR2 is related with angiogenesis in colorectal cancer tissues.
ObjectiveTo analyze expressions of interleukin-6 (IL-6) and microsatellite instability (MSI) in ulcerative colitis-associated colorectal cancer (UC-CRC) and investigate role of IL-6 and MSI in carcinogenesis of patients with UC.MethodsThe postoperative pathological data of patients with UC-CRC and patients with sporadic colorectal cancer (SCRC) admitted by Edong Healthcare Group from January 2013 to January 2019 were analyzed retrospectively. The expressions of MMR proteins, including hMLH1, hPMS2, hMSH2, and hMSH6, were detected by the immunohistochemical method. The serum IL-6 levels of the patients with UC, UC-CRC, SCRC and control patients (non-UC, non-UC-CRC, non-SCRC) were detected. The correlation between the IL-6 and MMR protein expression in the cancer tissue was analyzed.ResultsThere were 43 patients with UC, 17 UC-CRC, 55 SCRC, and 30 control patients. The total rate of MMR-deficient (dMMR) was 41.2% (7/17) in the patients with UC-CRC. There were significant correlations between the hMLH1 and hPMS2 protein expression deletion and between the hMSH2 and hMSH6 protein expression deletion (P<0.001). The serum level of IL-6 in the patients with UC-CRC was significantly higher than that in the patients with UC (t=4.97, P<0.001) and the patients with SCRC (t=5.26, P=0.006). The dMMR might be associated with the level of IL-6 in the patients with UC-CRC, which wasn’t associated with it in the patients with SCRC (rs=0.04, P=0.77).ConclusionsSimilar to SCRC, MSI also plays a role in occurrence and development of UC-CRC. dMMR in patient with UC-CRC is more common in co-expression deficiency of hMLH1 and hPMS2, as did hMSH2 and hMSH6. IL-6 is not involved in mechanism of MSI-related canceration of colorectal cancer, but it is speculated that IL-6 might be involved in occurrence of MSI of UC-CRC.
ObjectiveTo investigate the effect of Huaier extract on the proliferation, invasion, and ferroptosis pathways of colorectal cancer (CRC) cells. MethodsThe CRC cell line SW620 was cultured in vitro, and the cells were treated with Huaier extract solution at different concentrations (0, 5, 10, 20, and 50 mg/mL). The cell counting kit 8 was used to detect the proliferation of CRC cells at different concentrations to scree the test dose of the Huaier extract. The Transwell and the scratch assays were used to detect the cell invasion and migration. The reactive oxygen species (ROS), glutathione (GSH), and malondialdehyde (MDA) kits were used to detect the cellular oxidative stress level. The Western blot was used to detect the ferroptosis-related proteins levels, including glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (NRF2), and high mobility group box-1 (HMGB1). ResultsIn this study, it could statistically inhibit the proliferation of CRC cells after 48 h interfering with Huaier extract at 10, 20 mg/mL concentrations, so we chose 10, 20 mg/mL concentrations as the test dose, 0 mg/L as the control dose. Huaier extract effectively inhibited the migration and invasion abilities of SW620 cells in a dose-dependent manner (Transwell: F=480.0, P<0.001; scratch assay: F=24.3, P=0.001). The level of ROS in the SW620 cells increased with the increase of concentration in a dose-dependent manner (F=806.3, P<0.001). the level of GSH in the SW620 cells decreased with the increase of concentration in a dose-dependent manner (F=35.0, P=0.005), but the level of MDA was highest at 10 mg/mL (F=22.9, P=0.002) . Further the Huaier extract could effectively reduce the expressions of GPX4 (F=74.2, P<0.001), NRF2 (F=32.8, P=0.001), and HMGB1 (F=55.1, P<0.001) in a dose-dependent manner. ConclusionFrom the results of this study, Huaier extract at 10 and 20 mg/mL concentrations can inhibit the proliferation and invasion of CRC SW620 cells by inducing ferroptosis.
Objective To investigate the change of immunologic gene expression in cases of colorectal cancer with liver metastasis. Methods The total RNAs were extracted from tumor tissues of original lesions in 16 patients with colorectal cancer， DNA microarray was used to examine the change of immunologic gene expression in colorectal cancer patients with or without liver metastasis. Results Compared with samples without liver metastases， the expressions of 11 immunologic genes obviously down-regulated in the tumor tissues of colorectal cancer patients with liver metastasis， including：carboxypeptidase D；Fc fragment of IgE， high affinityⅠreceptor for gamma polypeptide；Fc fragment of IgG， low affinityⅢa receptor （CD16a）；free fatty acid receptor 2；interleukin 2 receptor gamma；protein tyrosine phosphatase receptor type C；complement factor B；major histocompatibility complex， classⅡ， DM alpha；major histocompatibility complex， classⅡ， DM beta；major histocompatibility complex， classⅡ， DQ alpha 1；granzyme B. The functions involved the growth and activation of immunologic cell， signal transduction， cell apoptotic， cell factors， receptors， complement， apoptotic， and immunogenicity of tumor cell. Conclusions Down-regulation of a various of immunologic gene expression in colorectal cancer patients with liver metastasis inhibits the function of immunology， and tumor cells escaped the destruction of immunology system results in metastasis.
ObjectiveTo explore the expressions of galectin-3 protein and CD105 protein in colorectal cancer and the relationship with clinicopathologic features. MethodsThe expressions of galectin-3 protein and CD105 protein 〔microvessel density (MVD)〕 were detected in 60 cases of colorectal cancer tissues, 30 cases of adenoma tissues, and 30 cases of normal mucosa tissues (at least 4 cm far from carcinoma) by MicrowaveEliVisionTM immunohistochemistry, and the relationship with clinicopathologic features was analyzed. ResultsThe expressions of galectin3 protein and MVD in normal mucosa tissues, adenoma tissues, and cancer tissues gradually increased (Plt;0.05). The expression of galectin-3 protein and MVD in colorectal cancer tissues were correlated to TNM stage, invasive depth, and lymph node metastasis (Plt;0.05， Plt;0.01), and the expression of glectin-3 protein was also correlated to differentiated degree (Plt;0.05). The expression of galectin-3 protein in colorectal cancer tissues was positively correlated to MVD (r=0.420， Plt;0.01). ConclusionsThe high expressions of galectin-3 protein and CD105 protein are correlated to the high invasion ability and lymph node metastasis, which may be potential sensitive index to predict the invasion and metastasis of colorectal cancer.
Objective To refine the loss of heterozygosity (LOH) on chromosome 7q21－22 and identify the new tumor suppressor gene(s) in colorectal tumorigenesis. Methods Fifteen polymorphic microsatellite markers were analyzed on chromosome 7 and another 5 markers were applied on chromosome 7q21-22 region in 83 cases of colorectal cancer and normal DNA by PCR. PCR products were electrophoresed on an ABI Prism 377 DNA sequencer. GeneScan 3.1 and Genotyper 2.1 software were used for LOH scanning and analysis. Results A distinct region of frequent allelic deletion was observed on chromosome, another 5 polymorphic microsatellite markers were applied to 7q21-22 and the minimal region of frequent LOH was established on 7q21-22 spanning the D7S657, D7S646 locus. Conclusion Through detailed deletion mapping studies, a critical and precise region spanning the D7S657, D7S646 locus is identified, which must contain one or more unknown tumor suppressor gene(s) on colorectal cancer.
ObjectiveTo investigate the effect of eukaryotic initiation factor 6 (eIF6) expression on invasion and metastasis of colorectal cancer cells and Wnt/β-catenin signaling pathway.MethodsImmunohistochemistry was used to detect the expressions of eIF6 protein in colorectal cancer tissues and paracancerous tissue. Sw837 cell lines with overexpression/knockdown eIF6 were constructed by transfection and divided into control group, empty plasmid group, overexpression group and knockdown group respectively. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) and Western blotting (WB) were used to verify the overexpression/knockdown of eIF6 in sw837 cells. WB was used to detect the expressions of β-catenin, glycogen synthase kinase-3β (GSK-3β), anaphase promoting complex (APC), zinc finger transcription factor SNAI (Snail), E-cadherin and Vimentin. Transwell invasion test, Scratch test and subcutaneous tumorigenesis test were used to detect the migration ability, invasion ability and tumorigenesis ability in vivo of cells. The pathological changes of the transplanted tumor were observed by HE staining.ResultsThe positive expression rate of eIF6 protein in cancer tissues was significantly higher than that in adjacent tissues (P<0.05). Compared with those in the control group, the protein expression levels of β-catenin, Snail and Vimentin in the overexpression group were higher, the protein levels of GSK-3β, APC and E-cadherin were lower, the ability of cell migration and invasion, and tumorigenicity in vivo were enhanced, the difference were statistically significant (P<0.05). The protein expression levels of β-catenin, Snail and Vimentin were lower in knockdown group, the protein levels of GSK-3β, APC and E-cadherin were higher, the ability of cell migration and invasion, and tumorigenicity in vivo were reduced, the difference were statistically significant (P<0.05).ConclusioneIF6 may promote the invasion and metastasis of colorectal cancer cells by activating Wnt/β-catenin signaling pathway.
ObjectiveTo analyze the relationship between occupational type of patients with colorectal cancer (CRC) and decision-making and curative effect of neoadjuvant therapy in the current version of the Database from Colorectal Cancer (DACCA). MethodsThe eligible CRC patients were collected from June 29, 2022 updated DACCA according to the screening criteria, in which the data items analyzed included: gender, age, BMI, blood type, marriage, occupation, neoadjuvant therapy, symptomatic changes, imaging changes, and tumor regression grade (TRG), and the occupations were classified into the mental labour group, physical labour group, and the unemployed and resident groups according to the type of labour, then compared the decision-making and curative effect of neoadjuvant therapy among the 3 groups. ResultsA total of 2 415 eligible data were screened, of which 1 160 (48.0%) were the most in the manual labour group, followed by 877 (36.3%) in the unemployed and resident group, and finally 378 (15.7%) in the mental labour group. The proportion of those who did not use targeted drugs was higher in both patients ≤60 years old and >60 years old [75.6% (958/1 267) vs. 82.5% (947/1 148)], with both differences being statistically significant (P=0.004 and P=0.019), and among patients >60 years old, the different occupational types were associated with symptomatic changes and imaging changes after neoadjuvant therapy, with the highest number of both changes to partial remission [71.5% (161/225) vs. 66.7% (148/222)], both differences being statistically significant (P=0.001 and P=0.017). ConclusionThe analysis results of DACCA data reveal that the occupational type of CRC patients was associated with the choice of neoadjuvant therapy, and that different occupational types were associated with changes in curative effect before and after neoadjuvant therapy in CRC patients >60 years old, which needs to be further analysis for the reasons.
ObjectiveTo identify genes associated with resistance to programmed cell death protein 1 (PD-1) inhibitors in colorectal cancer and elucidate their underlying mechanisms using bioinformatics approaches. MethodsGenes expression datasets were downloaded from the Gene Expression Omnibus (GEO) database to screen hypoxia-related genes (HRGs) and differentially expressed genes (DEGs). The intersection of HRGs and DEGs was defined as hypoxia-related differentially expressed genes (HDGs). The gene expression data of patients with colorectal cancer from The Cancer Genome Atlas (TCGA) were analyzed using Pearson correlation to identify the PD-1-related genes, further the STRING analysis (minimum interaction score was greater than 0.7) and Cytoscape were subsequently employed to screen the key PD-1-related genes. The relation between the screened key PD-1-related genes and the prognosis of colorectal cancer patients was analyzed to screen out the target genes. The real-time fluorescence reverse transcription quantitative polymerase chain reaction was used to analyze the expression of the target genes in the cancer tissues and their corresponding adjacent tissues of 20 patients with colorectal cancer. The Kaplan-Meier Plotter database and the ROC Plotter database were used to analyze the relation between the high and low expression of the target genes and the prognosis in different patients. The significance level was set as α=0.05. ResultsA total of 651 HRGs and 329 DEGs were screened out. By taking the intersection of these two sets, 37 HDGs were obtained for subsequent analysis. Through Pearson correlation analysis, 25 key PD-1-related genes were screened out and 10 and 14 key PD-1-related genes were screened out by the MCC algorithm and the MCODE algorithm respectively. By taking the intersection of these three sets, 3 key PD-1-related genes were obtained, then survival analysis, the Aurora kinase A (AURKA) gene was finally screened out as the target gene. The expression level of the AURKA gene in the pan-cancer patients who responded to PD-1 inhibitor treatment was significantly higher than that in non-responders (P＜0.001), and was significantly lower in the six colorectal cancer cells treated with hypoxia than in six colorectal cancer cells treated with normoxia (P＜0.001). The AURKA expression in the colorectal cancer tissues was significantly higher than that in the corresponding adjacent colorectal tissues (P=0.008). The overall survival of pan-cancer patients with high AURKA expression was better than that of those with low AURKA expression [HR (95%CI)=0.67 (0.49, 0.93), P=0.015]. Among the colorectal cancer patients with MMR deficiency, the patients with low AURKA gene expression had worse overall survival [HR (95%CI)=2.596 (1.028, 6.332), P=0.043] and recurrence-free survival [HR (95%CI)=4.201 (1.092, 16.150), P=0.037] as compared with those with high AURKA gene expression. The low AURKA expression was associated with significantly worse overall survivals in the colorectal cancer patients harboring wild-type or mutant TP53, BRAF, and KRAS as compared with high AURKA expression (P＜0.05), while no statistically significant difference was found in the overall survival of the normal MMR patients between with high AURKA expression and low AURKA expression (P=0.307). ConclusionThe results of this bioinformatics analysis suggest that hypoxia down-regulated AURKA expression, and low AURKA expression is associated with worse prognosis in colorectal cancer patients, and worse reactivity and prognosis in patients treated with PD-1 inhibitors.