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Objective:To investigate the clinical characteristics and prognosis of CpG island methylator phenotype (CIMP+ ) colon cancer, and the significance of CIMP status in the diagnosis and prognosis prediction in defective mismatch repair (dMMR) colon cancer.Methods:The keywords "colorectal cancer" "patient" and "CpG Island Methylator Phenotype" were used to search the Gene Expression Omnibus (GEO) database, and the GSE39582 was obtained, which included the clinical data of 585 patients with colorectal cancer and the sequencing data of the whole transcriptome of the tumor tissues. After excluding 72 cases with missing CIMP values, 513 cases were included for further analysis, including 278 males and 235 females, with a mean age of (67±13) years. According to the CIMP status, they were divided into CIMP+ group ( n=93) and CIMP-group ( n=420), then compare the differences in clinical characteristics, the Kaplan-Meier survival curves were plotted to compare the overall survival and disease-free survival; 71 dMMR cases were divided into CIMP+ group ( n=43) and CIMP-group ( n=28), and the K-M curves were plotted to analyze the differences in overall survival (OS) and disease free survival (DFS). Comparisons between groups were performed by t-test, χ2 test or Mann-Whitney U nonparametric test, and the difference in survival curves was tested by Long-rank test. Results:Patients in the CIMP+ group were significantly older than those in the CIMP-group [(70.84±12.60) years vs (66.21±13.08) years, t=3.18, P=0.002]. Right colon tumors originating from the CIMP+ molecular pathway were 9.3 times more likely to be CIMP+ than those of the left colon cancers ( OR=9.3, 95% CI: 5.2-17.9). BRAF mutant colon cancer originating from CIMP+ was 215.2 times more common than BRAF wild-type colon cancer originating with CIMP+ ( OR=215.2, 95% CI: 53.2-1906.7); and patients with dMMR colon cancer originated 12.8 times more common than patients with pMMR ( OR=12.8, 95% CI: 7.0-23.9). The difference between the CIMP+ and CIMP-groups was not statistically significant in terms of overall survival and disease-free survival ( P=0.590, 0.220). In the dMMR colon cancer subgroup, CIMP status did not correlate with patients′ overall survival and disease-free survival ( P>0.05). Conclusions:CIMP+ colon cancer patients were mostly of advanced age, with tumors originating from the right colon, mostly combined with BRAF gene mutations, and manifested as mismatch repair-deficient colon cancers. CIMP status had no correlation with TNM stage and survival of colon cancers patients. There was no significant difference in the survival between dMMR colon cancers caused by CIMP+ and those caused by MMR gene mutations.
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Objective:To investigate the effect of obstruction on the prognosis and possible mechanisms in colorectal cancer patients.Methods:Among 1574 cases of colorectal cancer who were treated in Beijing Friendship Hospital, Capital Medical University from January 2003 to December. 2014, 194 cases had preoperative intestinal obstruction. Firstly, described the clinical characteristics of 194 patients with obstruction, then COX multivariate regression analysis was performed on the 1574 colorectal cancer cohort to confirm whether the preoperative obstruction was independent predictor for the overall survival. Finally, propensity score matching method was used to match obstruction and non-obstruction cases, then compared overall survival difference.Results:In 194 cases of obstructive colorectal cancer, 60.3% and 37.1% of the tumors were located in the left and right respectively. The 55.7% of the patients had tumors larger than 5 cm in diameter, the median survival time was 39.7 months (95% CI: 28.3-60.4). Multivariate COX analysis, after adjusted for related confounding factors, found that preoperative obstruction is still an independent risk factor for poor prognosis ( HR=1.41, 95% CI: 1.01-1.97). After propensity score matching, 140 and 560 patients were included in the obstructive group and the non-obstructive group. The two groups were more balanced in most baseline characteristics. The median survival time of the two groups was 42.4 and 116.3 months ( P<0.001), the overall survival of obstructive patients was significantly worse than that of non-obstructive patients. Conclusions:Preoperative obstruction is an independent risk factor for poor prognosis of colorectal cancer. This may be due to the difficulty of surgery and low radical cure rate for obstructive colorectal cancer.
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Objective:To analyze the negative effect of prolonged postoperative ileus on postoperative recovery in patients underwent open alimentary tract surgery.Methods:This study was a retrospective cohort study. The subjects of the study were patients who underwent open gastrointestinal surgery at the General Surgery Department of Beijing Friendship Hospital, Capital Medical University from October 2016 to November 2018. According to the PPOI diagnostic criteria proposed by the University of Auckland, the included patients were classified as PPOI Group ( n=14) and non-PPOI group ( n=112). The postoperative complications, postoperative hospital stay and medical expenses during hospitalization were selected as the study endpoint indicators. T-test or Fisher′s exact test were performed to compare the differences between the two groups, and linear regression analysis was used to explore the independent effects of PPOI on hospital stay and medical expenses. Results:The incidence of PPOI in this study cohort was 11.1%. The total postoperative complications occurred more frequent in PPOI group (64.29% vs 38.39%, P=0.08). The average postoperative hospital stay of patients in the PPOI group was longer than that in non-PPOI group [(21.21±14.83) d vs (13.98±14.21) d, P=0.070]. Adjusting for various possible confounding factors, the PPOI regression coefficient beta (95% CI) that affects the length of hospital stay was [-0.43 (-7.16, 6.3), P=0.90]. The average medical cost of patients in the PPOI group was more than that in non-PPOI group [(104 389.64±52 427.66)元比(79 111.41±50 832.29)元, P=0.070]. Adjusting for various possible confounding factors, the PPOI regression coefficient beta (95% CI) that affects medical expenditure was [-134.12 (-21656.85, 21388.62), P=0.99]. Conclusions:Prolonged postoperative ileus leads to delayed postoperative recovery, which is related to increased postoperative complications, hospital stay duration and medical cost. But it needs further confirmation from large sample data.
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Objective:To investigate the relationship between systematic immune-inflamma-tion index(SII) and clinicopathological characteristics for colorectal cancer.Methods:The retrospec-tive cohort study was conducted. The clinicopathological data of 513 patients with colorectal cancer who were admitted to the Beijing Friendship Hospital of Capital Medical University from February 2019 to May 2021 were collected. There were 311 males and 202 females, aged (64±12)years. Observation indicators: (1) SII of colorectal cancer and relationship between SII and clinicopatholo-gical characteristics; (2) influencing factors for SII in colorectal cancer patients. According to the median of SII as the cutoff value, the patients were divided into high SII and low SII patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were represented as absolute numbers or percen-tages, and comparison between groups was conducted using the chi-square test. Measurement data with skewed distribution were represented as M( P25, P75), and comparison between groups was analyzed using the non-parameter rank sum test. Comparison of ordinal data was analyzed using the Mann-Whitney U non-parameter test. Variables with statistically significant differences between groups were included for further analysis. Pearson correlation coefficient analysis was used for continuous data, and Wilcoxon or Kruskal-Willas analysis was used for categorical data and Bonferroni correction was performed. Univariate and multivariate linear regression analyses were conducted. Results:(1) SII of colorectal cancer and relationship between SII and clinicopathological charac-teristics: the SII of 513 patients was 355(253,507). Taking the median SII 355 as the cutoff value, 257 of 513 patients with SII>355 had high SII and 256 cases with SII≤355 had low SII. Of high SII patients, the Karnofsky performance status(KPS) score, preoperative albumin(Alb), CA125, cases with tumor located at left or right hemicolon, tumor diameter, cases with laparoscopic assisted surgery or laparotomy (surgical approach), cases in stage T0, T1, T2, T3, T4 (pathological T staging), cases in stage Ⅰ, Ⅱ, Ⅲ, Ⅳ (pathological TNM staging) were 87±17, (37±5)g/L, 8.80 U/mL(5.90 U/mL, 14.15 U/mL), 174, 83, (5.2±2.8)cm, 208, 44, 5, 19, 25, 131, 63, 34, 98, 94, 14. The above indicators of low SII patients were 91±13, (38±4)g/L, 7.20 U/mL(5.40 U/mL, 10.03 U/mL), 200, 56, (4.0±1.9)cm, 221, 24, 8, 39, 35, 118, 45, 61, 84, 79, 12. There were significant differences in above indicators between the two groups ( t=-2.770, -3.211, Z=-3.799, χ2=7.050, t=5.324, χ2=6.179, Z=-3.390, -2.227, P<0.05). Results of Pearson correlation coefficient analysis showed that SII was positively correlated with the tumor diameter ( r=0.390, P<0.05), and negatively correlated with preoperative Alb ( r=-0.200, P<0.05). Results of Wilcoxon analysis showed that SII was 447(311,720), 352(251,493) in patients with tumor located at right hemicolon and left hemicolon, 439(284,640), 345(243,481) in patients undergoing laparotomy and laparoscopic assisted surgery, respectively. There were signi-ficant differences in SII between patients with tumor located at right and left hemicolon,between patients undergoing laparotomy and laparoscopic assisted surgery ( P<0.05). Results of Kruskal-Willas analy-sis showed that SII was 289(201,463), 296(210,398), 329(252,446), 369(265,505), 434(274,631) in patients with pathological T staging as stage T0, stage T1, stage T2, stage T3, stage T4, respectively, and 307(226,400), 380(260,503), 381(272,563), 376(273,634) in patients with patho-logical TNM staging as stage Ⅰ, stage Ⅱ, stage Ⅲ, stage Ⅳ, respectively. There were significant differences in SII between patients with different pathological T staging and between patients with different pathological TNM staging ( P<0.05). (2) Influencing factors for SII in colorectal cancer patients: results of univariate analysis showed that KPS score, preoperative Alb, CA125, tumor location, tumor diameter, patholo-gical N staging, pathological TNM staging were related factors for SII in colorectal cancer patients ( Beta=-3.5, -15.8, 3.7, 106.3, 51.8, 115.1, 104.7, 141.2,95% confidence interval as -5.7 to -1.3, -22.6 to -9.1, 1.8 to 5.5,34.6 to 177.9, 38.5 to 65.2, 40.5 to 189.7, 11.2 to 198.2, 46.9 to 235.9, P<0.05). Multivariate analysis showed that tumor location and tumor diameter were independent influencing factors for SII in colorectal cancer patients ( Beta=79.5, 42.5, 95% confidence interval as 8.4 to 150.7, 26.6 to 58.4, P<0.05). Conclusions:The SII is correlated with tumor location, tumor diameter, preoperative Alb, pathological T staging, pathological TNM staging. Preoperative hypoproteinemia indicates a high SII score. The longer of tumor diameter, right hemicolon tumor and high TNM staging indicate the more serious immune-inflammatory imbalance. Tumor location and tumor diameter are independent influencing factors for SII in colorectal cancer patients.
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Objective:The consensus molecular subtype (CMS) classification is based on the gene expression profiles, This article attempts to conduct a preliminary exploration and analysis of the clinical features of different CMS patients. We can give an individualized diagnosis and treatment for the patients.Methods:Seven GSE series of colorectal cancer gene expression profiles were downloaded by R software from the GEO database. A total of 1414 patients were included. Using the specific computational method published by Peter in 2017, the patients were divided into four groups: CMS1, CMS2, CMS3 and CMS4. The measurement data is expressed by Mean± SD, and the count data is expressed by n(%). The software of SPSS 18.0 was used to conduct analysis. Results:CMS1 tumors originated in the right colon (77.4%), while CMS2 mostly originated in the left colon (72.8%). The proportion of T 4 stage in CMS2 was 16.6%, while in the other three types was 23.3%, 29.3% and 24% respectively; the proportion of distant metastasis of CMS1 was the lowest (3.5%), while the distant metastasis rate of CMS4 was 18.2%. The KRAS mutation rates in CMS1 and CMS2 were 25.6% and 30.3% respectively, while in CMS3 it was up to 73.9%; the BRAF mutation rate in CMS1 was 45.5%, while the other three mutation rates were 0.6%, 6.2% and 5.9%, respectively; The average mutation rate of APC was 59.45%. Overall survival and progression-free survival analysis showed that the CMS4 interstitial type was the worst, while the CMS2 classic type had the best relative prognosis. Conclusions:CMS1 immunotype, the tumor has origin from right colon in female patients. MSI-H is often accompanied by BRAF gene mutation, this type patients has a refractory treatment response and poor prognosis. The classic CMS2 type is characterized by APC deletion mutation and Wnt activation, with good therapeutic effect and good prognosis. CMS3 metabolic type often harbor KRAS mutation, anti-EGFR treatment is not sensitive. Although this type is prone to relapse, but the chemotherapy is effective, so the overall survival prognosis is acceptable. CMS4 interstitial type with left colon tumor is prevalence. due to the activation of TGF-β and enhanced angiogenesis, this type tumor is prone to metastasis to distant site and has the worst prognosis.
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Objective:To analyze how the surface marker of breast cancer stem cell related to chemotherapy resistance and postoperative recurrence.Methods:The GEO public database GSE25066 and GSE32603 were used to extract clinical data including pathological evaluation of neoadjuvant chemotherapy, postoperative follow-up recurrence and recurrence time, and the expression levels of the following 18 breast cancer stem cell marker genes were extracted: CD44, CD24, EPCAM, CD49f, PROM1, CD61, ALDH1A1, CD10, ALDH1A3, ABCG2, RANK, CD47, CD166, SLUG, SOX2, SXO9, SOX10, MYC. A total of 488 patients with GSE25066 were divided into pathology compete response(pCR) group ( n=99) and residual disease (RD) group ( n=389) according to the pathological analysis. Another 418 patients with complete recurrence data was divided into recurrence group ( n=111) and non-recurrence group ( n=307), they were used for prognosis analysis. The effects of each tumor stem cell marker on chemotherapy sensitivity and tumor recurrence were analyzed by logistic, lasso and COX regression. The gene expression level of GSE32603 before and after neoadjuvant chemotherapy were used to analyze the changes after neoadjuvant chemotherapy in 166 patients, to determine the enrichment effect of chemotherapy on stem cells. Results:In chemotherapy response analysis, tumor stem cell markers CD44( OR=0.78, 95% CI: 0.63-0.98) and SANI2 ( OR=0.80, 95% CI: 0.68-0.93) were negatively correlated with neoadjuvant chemotherapy sensitivity, and CD24( OR=1.18, 95% CI: 0.97-1.47) was positively correlated with chemosensitivity. In the recurrence correlation analysis, the patients with CD44 + ( OR=1.22, 95% CI: 0.98-1.51), CD24 low( OR=0.94, 95% CI: 0.79-1.11) and SANI2( OR=1.17, 95% CI: 1.00-1.37) expression have a high recurrence rate. As chemotherapy progressed, the MME, CD49f, SOX10, MYC, and SOX9 ( P<0.05) showed an enrichment process. Conclusions:Breast cancer stem cell markers CD44 + CD24 - and SLUG can be used to predict the efficacy of neoadjuvant chemotherapy and recurrence after tumor treatment. They are relatively stable marker for studying breast cancer stem cells.
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Objective To observe the changes of PI3K/Akt signaling pathway and endoplasmic reticulum stress related protein GRP78 and CHOP in CCl4 induced liver fibrosis and to explore their effects on hepatic fibrosis.Methods Thirty SD rats were randomly divided into normal control group, 4 and 8 weeks liver fibrosis group (hypodermic injection of 40% CCl4).Pathological changes of liver tissue was observed by HE staining.The techniques of real-time PCR was applied to detect mRNA of GRP78 and CHOP in liver.Detected expression of Akt1, phospho-Akt1, GRP78 and CHOP protein by western blot.Meanwhile, the cell apoptosis in liver was detected by TUNEL.Results Compared with the normal control group, GRP78 and CHOP mRNA and protein in 4 and 8 weeks liver fibrosis group was increased(P<0.05), while expression of Akt1, phospho-Akt1 in 4 and 8 weeks liver fibrosis group was lower than that in normal control group(P<0.05).Compared with normal control group, the apoptosis of hepatocytes in 4 and 8 weeks liver fibrosis group was elevated (P<0.05).Conclusions PI3K/Akt signaling pathway and endoplasmic reticulum stress may play important roles in the induction of apoptosis of hepatocytes in rats with hepatic fibrosis.
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MicroRNAs (miRNAs) , a species of small noncoding RNA, could regulate gene expression bv binding to the 3'-untranslated region of target mR NA at post-transcription level.MicroRNAs play important roles in various human biological processes such as differentiation, cell proliferation, and apoptoMs.Abnormal expression of miRNAs is implicated in carcinogenesis and progression of various cancers, indicating that miRNAs could be served as molecular biomarkers for diagnosis and treatment of cancer.In this resiew, the author summarize the most common altered miRNAs expression profiles and their possible roles in promoting cell proliferation, tumor metastasis,and chemotherapeutic resistance in gastric cancer.
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<p><b>OBJECTIVE</b>Gastric cancer is a genetically heterogeneous disease that progresses via different oncogenes. MicroRNA (miRNA) can regulate oncogene expression at the post-translational level. In this review, we summarize the most commonly altered miRNAs and their possible roles in cancer initiation and progression in gastric cancer.</p><p><b>DATA SOURCES</b>Most articles were identified by searching PubMed online resources using the key terms of microRNA and gastric cancer.</p><p><b>STUDY SELECTION</b>Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected, and the 69 most important articles were cited finally.</p><p><b>RESULTS</b>A set of miRNAs are consistently deregulated in gastric cancer, although there is no clear miRNA expression profiles, such as miR-21 and miR-17 (∼92 clusters). These deregulated miRNAs play important roles in promoting cell proliferation, tumor metastasis, and chemotherapeutic resistance in gastric cancer by targeting different oncogenes. Clinical relevance of these deregulated miRNAs is proved to be associated with TNM stages, metastasis, and prognosis of gastric cancer patients. In addition, circulating miRNAs are promising noninvasive biomarkers for gastric cancer.</p><p><b>CONCLUSIONS</b>miRNAs have produced a novel paradigm in research in gastric cancer. These small molecules play macroroles in gastric cancer initiation and progression. These results will help us improve management of gastric cancer in future.</p>
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Animals , Humans , Disease Progression , Gene Expression Profiling , MicroRNAs , Genetics , Stomach Neoplasms , GeneticsABSTRACT
Objective To explore the feasibility of laparoscopic splenectomy (LS) in the management of ruptured spleen. Methods Laparoscopic splenectomy was performed in 8 cases of ruptured spleen in this hospital from August 2004 to May 2005. Results Laparoscopic splenectomy was accomplished successfully in 7 cases and a conversion to hand-assisted laparoscopic splenectomy (HALS) was needed in 1 case. The operation time was 150~200 min (mean, 180 min). The intraoperative blood loss was 600~5 500 ml (mean, 2 200 ml). There were 5 cases of type Ⅱ rupture and 3 cases of type Ⅲ rupture. The postoperative recovery was uneventful and no complications were encountered. Conclusions[WTBZ] Laparoscopic splenectomy is a safe and feasible option for the management of ruptured spleen.
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0.05).The expression of bcl-2 in sham group was significantly higher than that in GC and ADX groups(P0.05)was observed.The ratio of bax to bcl-2 in sham group was significantly lower than that in GC and ADX groups(P