1.Gut microbiota aids in differentiating proximal colorectal cancer in the combination of tumor markers
Tianchen HUANG ; Xiaodong HAN ; Yong ZHANG ; Kan LI ; Zhipeng GUO ; Lei LI ; Yachao WU ; Yanjun WANG ; Dongxiao BAI ; Jianan XIAO ; Jiangman ZHAO ; Fuyou ZHOU ; Weili LI
Chinese Journal of Laboratory Medicine 2024;47(4):444-450
Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.
2.Effects of Porphyromonas gingivalis infection and vitamin D pathway protein expression on survival and prognosis of patients with esophageal squamous cell carcinoma
Mengfan QIAN ; Jinyu KONG ; Yiwen LIU ; Wei SUN ; Fuyou ZHOU ; Shegan GAO
Acta Universitatis Medicinalis Anhui 2023;58(12):2024-2031
Objective To analyze the effects of Porphyromonas gingivalis(Pg)infection and expression of vitamin D pathway-related proteins on the survival and prognosis of patients with esophageal squamous cell carcinoma(ES-CC).Methods Pg infection and the expression of 24 hydroxylase(CYP24A1),1α hydroxylase(CYP27B1)and vitamin D receptor(VDR)in 173 ESCC tissues were detected by immunohistochemistry.The correlation between each index and the survival time of patients was analyzed.Results The positive rates of Pg,CYP24A1,CYP27B1 and VDR in ESCC were 43.35%,37.57%,20.23%and 21.97%,respectively.The 5-year survival time of ES-CC patients in the Pg+CYP24A1+CYP27B-VDR-high-risk group was shortened(P<0.05).Conclusion Pg infection and vitamin D pathway-associated proteins can be used as reliable indicators to predict the survival and prognosis of ESCC patients.
3.Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors
Lidong WANG ; Liuyu LI ; Xin SONG ; Xueke ZHAO ; Fuyou ZHOU ; Ruihua XU ; Zhicai LIU ; Aili LI ; Jilin LI ; Xianzeng WANG ; Liguo ZHANG ; Fangheng ZHU ; Xuemin LI ; Weixing ZHAO ; Guizhou GUO ; Wenjun GAO ; Xiumin LI ; Lixin WAN ; Jianwei KU ; Quanxiao XU ; Fuguo ZHU ; Aifang JI ; Huixiang LI ; Jingli REN ; Shengli ZHOU ; Peinan CHEN ; Qide BAO ; Shegan GAO ; Haijun YANG ; Jinchang WEI ; Weimin MAO ; Zhanqiang HAN ; Zhiwei CHANG ; Yingfa ZHOU ; Xuena HAN ; Wenli HAN ; Lingling LEI ; Zongmin FAN ; Ran WANG ; Yuanze YANG ; Jiajia JI ; Yao CHEN ; Zhiqiang LI ; Jingfeng HU ; Lin SUN ; Yajie CHEN ; Helin BAI ; Duo YOU
Chinese Journal of Internal Medicine 2022;61(9):1023-1030
Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.
4.The value of esophageal activity examination under X-ray fluoroscopy and chest CT in assessing the resectability of upper thoracic esophageal cancer
Jianwei CAO ; Mingfei GENG ; Fuyou ZHOU ; Dongshan ZHU ; Hui LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(09):1044-1048
Objective To investigate the value of esophageal activity examination under X-ray fluoroscopy and chest CT in evaluating the resectability of upper thoracic esophageal cancer. Methods A total of 221 upper thoracic esophageal carcinoma patients underwent radical operation between 2009 and 2015 in our hospital were enrolled, including 141 males and 80 females with a median age of 59 (47-79) years. Preoperative routine esophageal activity examination under X-ray fluoroscopy and chest enhanced CT were performed to determine whether the tumor had external invasion. The results of the two methods were compared with that observed during the operation. Results The number of patients with esophageal activity score 1-6 was 70, 85, 32, 29, 2 and 3, respectively. The area under the receiver operating characteristic (ROC) curve (AUC) of esophageal activity examination was 0.897 (95%CI 0.85-0.93, P<0.001), and the cut off value was >3. According to the ROC curve activity score, 4-6 points were considered as invasion, and 1-3 points were non-invasion. The sensitivity, specificity, accuracy and misdiagnosis rate of esophageal activity examination was 75.0%, 89.3%, 88.2%, 10.7%, respectively, and those of CT scan were 75.0%, 66.8%, 67.4%, 33.2%, respectively. Compared with CT scan, the specificity of esophageal activity examination was higher and the misdiagnosis rate was lower. Compared with the detection during the operation, 86.7% of patients with actual invasion of trachea and 85.7% of patients with actual invasion of other parts were in accordance with the esophageal activity examination results. Conclusion Esophageal activity examination under X-ray fluoroscopy can accurately predict the resectability of upper thoracic esophageal cancer, which is a useful supplement to chest CT examination, especially in the aspect of judging the relationship between lesions and the trachea.
5.Numerical Study on Low-Density Lipoprotein Transport and Deposition in Carotid Arteries and the Associated Factors
Journal of Medical Biomechanics 2020;35(5):E553-E561
Objective To investigate the transport and deposition behaviors of lowdensity lipoproteins (LDL) in the carotid artery and explore their associations with hemodynamic and morphological factors, so as to provide theoretical references for assessing the risk and predisposing regions of atherosclerosis based on the characteristics and associated factors of LDL deposition at the carotid artery wall. Methods Subject-specific computational models of the carotid artery based on medical images from six healthy volunteers were built, and the transport and wall deposition of LDL under pulsatile flow conditions were simulated, and finally the correlations of wall LDL concentration and total area of regions with LDL concentration polarization with flow velocity and morphological parameters of the carotid artery were quantitatively analyzed. Results Regions with significant LDL deposition often appeared in carotid sinus near distal end of the common carotid artery, with the degree and spatial distribution of deposition differing considerably among subjects. The degree of LDL deposition was determined mainly by flow velocity, i.e., the lower the flow velocity was, the higher the degree of LDL deposition and accordingly the larger the area of wall regions with LDL concentration polarization was; whereas the spatial distribution of LDL deposition was significantly affected by morphological characteristics (especially bifurcation eccentricity ratio) of the carotid artery, for example, the distribution patterns could be divided into two typical types (i.e., circular distribution, unilateral distribution) according to bifurcation eccentricity ratio. Conclusions Flow velocity and morphological characteristics of the carotid artery are major factors determining respectively the degree and spatial distribution of LDL deposition, and therefore subject-specifically measuring these parameters will provide useful information for screening individuals at high risk of atherosclerosis or identifying atheroprone regions.
6.Analysis of the effect and prognosis of lymph tracing in different lymph regions of esophageal cancer with nano carbon suspension
Jianwei CAO ; Mingfei GENG ; Fuyou ZHOU ; Dongshan ZHU ; Xiaoyu HUANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2020;36(11):686-689
Objective:In the operation of esophageal cancer, nano carbon suspension was used for lymph tracing, and the effect of lymph tracing in different regions and its influence on prognosis were analyzed.Methods:From July 2013 to August 2014, 100 patients under esophageal cancer surgery in our department were analyzed. Randomly divided into experimental group and control group, 50 cases each. During the operation, nano carbon suspension was used to trace the lymph nodes in the experimental group, while conventional operation was only used in the control group. The general baseline data, the number of lymph nodes and positive lymph nodes in each region in the two groups were compared, the lymph node metastasis and survival were followed up, and the prognosis of the two groups were compared.Results:There was no significant difference in baseline data between the two groups( P>0.05). The average number of lymph nodes in the experimental group was 18.6 per case, and that in the control group was 15.1 per case. There was significant difference between the two groups( P=0.003). There was no significant difference in the number and degree of metastasis between the two groups( P=0.233, P=0.463). The effect of nano carbon suspension on tracing lymph nodes around the lower mediastinal esophagus was better. In the experimental group, 4.38 lymph nodes were removed in this area on average, 0.34 of which were metastatic lymph nodes. In the control group, 2.52 lymph nodes were removed in each case on average, 0.10 of which were metastatic lymph nodes. The comparison between the two groups was significantly higher than that of the control group( P=0.001, P=0.011 respectively). In the upper mediastinum, abdominal cavity and other mediastinal lymph nodes, there was no significant difference in the number of lymph nodes, the number of lymph nodes and the degree of metastasis between the two groups( P>0.05). The time of lymph node metastasis in the experimental group was significantly later than that in the control group( P=0.048, log rank test). There was no significant difference in survival time between the two groups( P=0.692, log rank test) . Conclusion:The results show that the nano carbon suspension has a good effect on the lymph node tracing during the operation of esophageal cancer, and the effect on the lymph node tracing around the lower mediastinal esophagus is better.In the area close to the lung drainage area, the tracer effect is poor, and it has certain effect in reducing or delaying lymph node metastasis.
7.Molecular basis and precision medicine for interactions of genetic and environmental risk factors in esophageal cancer
Lidong WANG ; Xin SONG ; Xueke ZHAO ; Minjie WU ; Fuyou ZHOU
Chinese Journal of Clinical Oncology 2016;43(12):515-520
Esophageal cancer is a unique malignant disease in China. A fundamental difference exists between the Chinese population and the western population on esophageal cancer in terms of epidemiology, histogenesis, and carcinogenic risk factors. Therefore, ap-plying the western academic achievements to Chinese is difficult. Thus, Chinese scientists have the responsibility to conquer esopha-geal cancer in China. This article reviews the progress of esophageal cancer focused on the molecular mechanism for interactions of ge-netic and environmental risk factors and human esophageal multistage carcinogenesis.
8.Correlation of triggering receptors expressed on myeloid cells-1 with the oncogenesis and progression of hepatocellular carcinoma.
Wanyun LI ; Na ZHANG ; Yurong OU ; Zhengguang ZHOU ; Fuyou ZHAO ; Qiong WU ; Yan YANG
Journal of Southern Medical University 2015;35(12):1705-1720
OBJECTIVETo investigate the role of triggering receptors expressed on myeloid cells-1 (TREM-1) in the oncogenesis and progression of hepatocellular carcinoma (HCC).
METHODSThe expression and localization of TREM-1 were detected by immunohistochemistry in 76 specimens of HCC, 33 specimens of liver cirrhosis, 30 specimens of hepatitis and 20 normal liver tissues. The association between TREM-1 expression and the clinicopathologic parameters of HCC was analyzed. Human normal hepatic cell line LO2 and HCC cell line SMMC-7721 were examined for TREM-1 expression pattern using RT-PCR and Western blotting.
RESULTSAll the normal liver samples showed negative expression of TREM-1 protein, which was significantly up-regulated in the other 3 tissues. The positivity rates of TREM-1 expression were not significantly different between hepatitis, cirrhosis and HCC tissues [20.00% (6/30), 24.24% (8/33), and 21.05% (16/76), respectively; Χ² =0.195, P=0.907]. Different from chronic hepatitis and liver cirrhosis tissues where TREM-1 expression was located mainly in the nucleus and occasionally in the cytoplasm of the hepatocytes, HCC tissues showed a cellular localization of TREM-1 protein almost exclusively in the cytoplasm. In HCC, TREM-1 expression was negatively correlated with the histological grade of the tumor (r=-0.261, P=0.023) but not related with the patients' age, gender, tumor size, clinical stage, pre-existing hepatitis and cirrhosis, lymph node metastasis, or intrahepatic vascular embolism (all P>0.05). In the in vitro experiments, low levels of TREM-1 mRNA and protein expressions were detected in LO2 cells line, but their expressions were markedly up-regulated in SMMC-7721 cells.
CONCLUSIONAberrant enhancement of the expression and cytoplasmic accumulation of TREM-1 may correlate closely with the oncogenesis and progression of HCC.
Carcinogenesis ; Carcinoma, Hepatocellular ; metabolism ; Cell Line ; Cell Line, Tumor ; Cell Nucleus ; Cytoplasm ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Hepatocytes ; metabolism ; Humans ; Immunohistochemistry ; Liver Cirrhosis ; Liver Neoplasms ; metabolism ; Membrane Glycoproteins ; metabolism ; Receptors, Immunologic ; metabolism ; Triggering Receptor Expressed on Myeloid Cells-1 ; Up-Regulation
9.The characteristics of EPPB41L3 methylation in esophageal squamous cell carcinoma tissues and in plasma and the clinical significance of this methylation
Weibin XIONG ; Xufeng LI ; Chunyu JIANG ; Jiren ZHANG ; Fuyou ZHOU ; Li YU ; Yanfang ZHENG
The Journal of Practical Medicine 2015;31(14):2271-2275
Objective To detect EPPB41L3 methylation frequency difference between esophageal squamous cell carcinoma (ESCC) tissues and the normal tissues and between ESCC patients′plasma and healthy volenteers′plasma, and to analyze the correlation with clinicopathological parameters. Methods We collected esophageal squamous cell carcinoma tissues (n = 42 patients) and adjacent surrounding normal tissues (n = 42 patients), and plasma from 42 patients with ESCC and from 50 healthy individuals. We used methylation specific PCR (MSP) combined with agarose gel electrophoresis to detect the methylation status of the EPB41L3. We used the SPSS 13.0 software for statistical analysis by χ2 test and Fisher′s exact test. Results EPB41L3 frequency of methylation was significantly higher in tumor tissues than in the adjacent tissues (59.5% vs. 4.8%), the difference was statistically significant (χ2 = 28.873, P < 0.001). For plasma, EPB41L3 methylation frequency was 31.0%in cancer patients, while was not detectable in the healthy volunteers. Methylation of EPB41L3 in tissues was more frequently found in patients with tumor size of ≥ 5 cm or T3 than in patients with tumor size of < 5 cm or T1-2. Conclusions The methylation frequency of EPB41L3 is higher in ESCC tissues than in control normal tissues, and higer in plasma from ESCC patients than that from the healthy volunteers. EPB41L3 methylation is more frequently found in patients with more advanced disease.
10.Role of miR-129-5p in regulation of epithelial-mesenchymal transition of peritoneal mesothelial cells
Xun ZHOU ; Fuyou LIU ; Ying LUO ; Dan TANG ; Shikun YANG ; Lin SUN ; Li XIAO
Chinese Journal of Nephrology 2015;31(4):269-276
Objective To investigate the role of microRNA-129-5p (miR-129-5p) in the regulation of epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs) isolated from peritoneal dialysate effluents and TGF-β1 induced HPMCs line.Methods The isolated cells were cultured from peritoneal dialysate effluents overnight of 10 patients just started PD and 12 patients with PD over 6 months.Taqman PCR assay was used to determine the expression of miR-129-5p in the HPMCs.Moreover,the expression of miR-129-5p in HPMCs induced by 5 μg/L TGF-β1 for 0-72 h was also detected by Taqman PCR.HPMCs were pre-transfected with miR-129-5p precursor (pre-mir-129-5p) to overexpress miR-129-5p,then incubated with TGF-β1 for 48 h,and the expression of EMT associated gene and protein was detected by real-time PCR,Western blotting and immunofluorescence,respectively.Furthermore,the effect of TGF-β1 on the expression of Smad interacting protein-1 (SIP1) and the regulation of pre-miR-129-5p on the SIP1 expression also were investigated.Results MiR-129-5p expression significantly down-regulated in the HPMCs isolated from PD patients over 6 months than from PD start patients(P < 0.01).Similarly,TGF-β1 remarkably decreased miR-129-5p in HPMCs lines on time-dependent manner (P < 0.01).Pre-mir-129-5p dramatically restored the expression of epithelial marker E-cadherin,while inhibited the expression of Vimentin,a mesenchymal marker,in HPMCs induced by TGF-β1 (all P < 0.01).In addition,TGF-β1 increased SIP1 expression in HPMCs time dependently,while the high level of SIP1 protein was obviously repressed after transfected of pre-miR-129-5p (P < 0.01),but there was no obvious change of its mRNA expression.Conclusion MiR-129-5p modulates EMT formation of HPMCs in PD process,possibly by posttranscriptional inhibition of SIP1.Targeting miR-129-5p/SIP1 may provide a new approach for the prevention and treatment of peritoneal fibrosis during PD.

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