1.Cultivation of research and innovation ability among medical undergraduates in the context of "Double First-Class" discipline construction
Jianwei WANG ; Deqiang WANG ; Qiling PENG
Chinese Journal of Medical Education Research 2024;23(8):1075-1079
In order to improve the research and innovation ability of medical undergraduates, this article summarizes the main problems in the cultivation of innovation ability among medical undergraduates through literature research and the authors' experience in the teaching and research from the three aspects of limited knowledge system, a lack of professional guidance for research training, and poor integration of scientific research into clinical practice. It is proposed that the methods of developing the ability to search and read scientific literature among undergraduate students, enhancing interdisciplinary activities and joint training, and building a teaching team of clinicians with extensive research experience can help to achieve a more effective integration of theoretical research and clinical practice and thus cultivate the research and innovation ability among medical students. These initiatives have made significant achievements and provide a reference for decision making in undergraduate research training in medical colleges and universities, as well as guidance for talent cultivation in medical colleges and universities in China.
2.Successful delivery in a pregnancy complicated by primary cardiac angiosarcoma with ovarian metastasis: a case report
Xingyu MAO ; Xi PENG ; Ting SONG ; Jianwei HUANG
Chinese Journal of Perinatal Medicine 2024;27(11):956-958
This article reported a case of successful delivery in a woman with right atrial angiosarcoma and ovarian metastasis. At 31 weeks of gestation, the pregnant woman experienced dyspnea, osphyalgia, nausea, and vomiting. An echocardiogram performed at a local hospital indicated a hypoechoic mass in the right atrium. On December 12, 2023 (32 weeks of gestation), she was transferred to the Third Affiliated Hospital of Guangzhou Medical University. On admission, cardiac ultrasound suggested an irregular slightly high echo in the right atrium, and MRI indicated a malignant tumor. On the day of admission, the patient underwent cardiac exploratory surgery and cesarean section. An enlarged left ovary was found during the surgery, and postoperative pathology confirmed primary right atrial angiosarcoma with left ovarian metastasis. The patient was transferred to the intensive care unit for further treatment. At the request of her family, she was discharged after her condition improved (11 d after the surgery). A male infant who had shallow breathing but did not cry at birth was delivered via cesarean section. He was transferred to the neonatal department for intubation and positive pressure ventilation with a resuscitation bag and was discharged 25 d after birth. The patient was lost to follow-up after discharge.
3.Long non-coding RNA CTC-338M12.4 inhibition on activation of JAK/STAT signaling pathway via miRNA-27a-5p makes cell cycle arrest, cell proliferation and migration inhibition in tongue squamous cell carcinoma
Xin PENG ; Jin WANG ; Yan XIONG ; Xiaoquan LUO ; Hui GUO ; Jianwei PENG
Cancer Research and Clinic 2024;36(11):801-807
Objective:To investigate the expression level of long non-coding RNA (lncRNA) CTC-338M12.4 in tongue squamous cell carcinoma tissues, and its effects on the cell cycle, cell proliferation, and migration of tongue squamous cell carcinoma cells in vitro as well as its molecular mechanisms.Methods:The Gene Expression Omnibus (GEO) database was used to obtain the lncRNA series data set GSE139869, and the differential expression of CTC-338M12.4 in tongue squamous cell carcinoma tissues and adjacent tissues was analyzed. The transcriptional expression levels of CTC-338M12.4 in human immortalized oral keratinocytes (HOK) and tongue squamous cell carcinoma cell lines HN13, TSCCa, CAL-27, Tca8113, SCC15 were detected by using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). CAL-27 cells with the lowest expression level of CTC-338M12.4 were selected and were divided into the control group (co-transfected with vectors containing negative sequence) and CTC-338M12.4 group (co-transfected with CTC-338M12.4 overexpression vectors). The proliferation ability of CAL-27 cells in each group was detected by using cell colony formation assay, and the cell cycle distribution of CAL-27 cells was detected by using flow cytometry. The migration ability of CAL-27 cells was detected by using scratch test. The lncACTdb database was used to predict the complementary binding sites between CTC-338M12.4 and miRNA-27a-5p (miR-27a-5p), and dual-luciferase reporter gene assay was used to verify. The expression level of miR-27a-5p in CAL-27 cells of all groups was detected by using qRT-PCR. The protein expression level of related factors on JAK/STAT signaling pathway in CAL-27 cells of all groups was detected by using Western blot.Results:Analysis of GEO database data showed that transcriptional level CTC-338M12.4 in tongue squamous cell carcinoma tissues was lower than that in adjacent tissues, and the difference was statistically significant ( P < 0.01). Transcriptional level CTC-338M12.4 in tongue squamous cell carcinoma HNl3, TSCCa, CAL-27, Tca8113, and SCC15 cells was lower than that in HOK cells, and the differences were statistically significant (all P < 0.05). The transcriptional level relative expression level of CTC-338M12.4 in CAL-27 cells in the CTC-338M12.4 group was higher than that in the control group, and the difference was statistically significant ( P < 0.01). Cell colony formation assay showed that the colong number of CAL-27 cell in the CTC-338M12.4 group was less than that in the control group [(51±10) vs. (114±21)], and the difference was statistically significant ( t = 2.71, P = 0.035). Flow cytometry showed that the proportion of G 0/G 1 phase cells in CAL-27 cells in the CTC-338M12.4 group was higher than that in the control group [(64±3)% vs. (43±4)%], and the difference was statistically significant ( t = 4.87, P = 0.003). The scratch test showed that when scratching, the scratch width of both groups was similar ( P > 0.05); after scratch for 25 h, the scratch width of CAL-27 cells in the CTC-338M12.4 group was wider than that in the control group [(133±15) μm vs. (64±10) μm], and the difference was statistically significant ( t = 3.78, P = 0.009). The dual luciferase reporter gene assay showed that the relative luciferase activity of CAL-27 cells co-transfected with wild-type CTC-338M12.4 sequence and miR-27a-5p sequence was lower than that of CAL-27 cells co-transfected with wild-type CTC-338M12.4 sequence and miR-27a-5p irrelevant sequence, and the difference was statistically significant ( P < 0.001). The relative expression level of transcriptional level miR-27a-5p of CAL-27 cells in the CTC-338M12.4 group was lower than that in the control group, and the difference was statistically significant ( P = 0.003). Western blot showed that the protein expression levels of JAK/STAT signaling pathway p-JAK, p-STAT, p-Raf, p-ERK, and p-mTOR were lower than those in the control group. Conclusions:The level of lncRNA CTC-338M12.4 is low in tongue squamous cell carcinoma. CTC-338M12.4 mediates the inactivation of JAK/STAT signaling pathway via inhibiting miR-27a-5p expression in tongue squamous cell carcinoma CAL-27 cells, thereby leading to cell cycle arrest and inhibiting the cell proliferation and migration of CAL-27 cells.
4.Malaria re-importation risk and control needs in the border region, Yunnan
ZHOU Yaowu ; DING Chunli ; YANG Zhongping ; LIN Zurui ; TIAN Peng ; SUN Xiaodong ; DUAN Kaixia ; CHEN Qiyan ; ZHAO Yulong ; XU Jianwei ; ZHOU Hongning
China Tropical Medicine 2024;24(4):394-
Recently, malaria incidence has sharply resurgence in the border area of northern Myanmar, with the parasite incidence rate in 2023 being 21.47 times (95% CI: 18.84-24.48) that of 2019 in Kachin State's Razan and nearby areas. This resurgence caused the number of imported malaria cases to increase from 188 in 2019 to 398 in 2023 in Yunnan Province. In addition to the impact of military conflict, the border malaria joint prevention and control cooperation mechanism and malaria control measures established between China and Myanmar have failed to be implemented effectively due to the impact of the international COVID-19 epidemic. Hence, it is recommended that relevant departments evaluate the quality and effectiveness of the current cross-border transmission measures for malaria in the China-Myanmar border area from a technical perspective, and provide a large demand for primaquine, which can block the spread of malaria and cure vivax malaria, in response to the current prevalent characteristics of vivax malaria predominating in northern Myanmar. Moreover, to effectively reduce the mortality of imported malaria patients and prevent re-importation and transmission, it is necessary to enhance clinical physicians' knowledge, awareness, and vigilance regarding malaria diagnosis and treatment in the Yunnan border region, as well as China's ability and quality of appropriate response to imported malaria.
5.Expression and clinical significance of long non-coding RNA differentially expressed genes, micro RNA-181a-5p and autophagy-related protein 5 in primary gouty arthritis
Jianwei GUO ; Tianyi LEI ; Peng WANG ; Zeng ZHANG ; Guilin JIAN ; Quanbo ZHANG ; Yufeng QING
Chinese Journal of Rheumatology 2024;28(5):303-311
Objective:To explore the expression and clinical significance of long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE), microRNA-181a-5p (miR-181a-5p) and autophagy related 5 (ATG5) in the peripheral blood of patients with gouty arthritis (GA) patients.Methods:The clinical data, laboratory parameters and peripheral blood samples were collected from 40 patients with acute gout (AG), 40 patients with intermittent gout (IG) and 50 healthy subjects (HC). The expression levels of lncRNA CRNDE, miR-181a-5p and ATG5 mRNA were detected by real-time fluorescence quantification (RT-qPCR) and the expression level of ATG5 protein was detected by Western-blot. The expression levels of lncRNA CRNDE, miR-181a-5p, ATG5 mRNA were compared among the three groups and correlated with clinical indices, and a subject operating characteristic curve (ROC) was constructed to assess the value of lncRNA CRNDE, miR-181a-5p, ATG5 mRNA in the diagnosis of gout. Measurements conforming to normal distribution were analyzed using t test or ANOVA, data with non-normal distribution was analyzed using Mann-Whitney U test or Kruskal-Wallis H test, correlation analysis between variables was analyzed using Spearman's analysis, and the diagnostic value of each indicator was analyzed using ROC curve. Results:① The differences in the expression of lncRNA CRNDE, miR-181a-5p, and ATG5 mRNA between the three groups were statistically significant ( H=32.12, 57.73, 68.32, all P<0.001). Among them, lncRNA CRNDE expression level in the AG group was significantly higher than that in the IG group and healthy control group [61.95(11.39, 108.30)×10 -3, 25.71(15.40, 38.40)×10 -3, 13.80(3.97, 23.99)×10 -3; Z=-3.24, P=0.001; Z=-5.03, P<0.001], and the expression level of IG group was higher than that of healthy control group( Z=-3.56, P<0.001); miR-181a-5p and ATG5 mRNA expression levels in AG group were significantly lower than those in IG group and healthy control group [miR-181a-5p: 39.81(31.22, 69.38)×10 -3, 60.74(44.19, 90.35)×10 -3, 121.30(101.50, 316.90)×10 -3; Z=-3.01, P=0.030; Z=-6.93, P<0.001. ATG5 mRNA: 4.52(2.31, 26.63)×10 -3, 43.63(13.72, 102.70)×10 -3, 153.90(66.62, 365.80)×10 -3; Z=-5.47, -7.36, all P<0.001)], which were expressed at lower levels in the IG group than in the healthy controls ( Z=-5.25, -4.47, all P<0.001). The difference of ATG5 protein expression level among the three groups expressed was statistically significant ( F=6.24, P=0.030), and the AG group was higher than the healthy control group, and the difference was statistically significant [(0.96±0.13) vs.(0.61±0.04), t=4.25, P=0.013], but the difference between the IG group (0.78±0.15) and the AG group and the HC group was not statistically significant ( t=1.51, P=0.206; t=1.85, P=0138). ② Spearman correlation analysis showed that lncRNA CRNDE was negatively correlated with the expression levels of miR-181a-5p and ATG5 mRNA in gout patients ( r=-0.49, P<0.001; r=-0.35, P=0.002); miR-181a-5p was positively correlated with ATG5 mRNA expression levels ( r=0.64, P<0.001); lncRNA CRNDE expression level was positively correlated with ESR and WBC ( r=0.49, P<0.001; r=0.43, P=0.001); miR-181a-5p expression level was negatively correlated with ESR and WBC ( r=-0.29, P=0.009; r=-0.35, P=0.002), and ATG5 mRNA expression levels were negatively correlated with ESR, WBC, and GR ( r=-0.26, P=0.021; r=-0.26, P=0.024; r=-0.27, P=0.021). In the AG group lncRNA CRNDE was positively correlated with ESR and WBC ( r=0.36, P=0.022; r=0.36, P=0.026) and miR-181a-5p was negatively correlated with WBC ( r=-0.34, P=0.038) ③ ROC curve showed that the areas under ROC curve of lncRNA CRNDE, miR-181a-5p and ATG5 mRNA expression levels to predict gout were 0.764, 0.875 and 0.864, respectively. The area under ROC curve of gout predicted by the three combined was 0.928. Conclusion:lncRNA CRNDE, miR-181a-5p, and ATG5 may be involved in the pathoge-nesis of primary gouty arthritis, and are potential biological parameters for studying the pathogenesis of gout.
6.Yiqi Wenyang Huwei Decoction in Treatment of Bronchial Asthma in Rats by Regulating TGF-β1/Smad3 Signaling Pathway
Xiaopu SU ; Wei TANG ; Chao YE ; Qiangqiang YU ; Peng SUN ; Yuping YANG ; Jianwei YU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):98-105
ObjectiveTo investigate the effect and mechanism of Yiqi Wenyang Huwei decoction (YWHD) on airway inflammation in bronchial asthma (BA) rats based on transforming growth factor-β1 (TGF-β1)/SMAD family member 3 (Smad3) signaling pathway. MethodSixty male SD rats were randomly divided into a normal group, a model group, a dexamethasone (DEX) group, and low-, medium-, and high-dose YWHD groups, with 10 rats in each group. The BA model was induced by intraperitoneal injection of 1 mL of ovalbumin (OVA)-aluminum hydroxide suspension for sensitization, followed by nebulization with 2% OVA. One hour before daily OVA nebulization, the control group was treated with saline, the DEX group with DEX solution at 0.2 g·L-1, and the low-, medium-, and high-dose YWHD groups with YWHD at 1, 2, 4 g·mL-1, respectively. General conditions and lung function were observed. Bronchoalveolar lavage fluid (BALF) and serum were collected to count inflammatory cells in BALF and measure immunoglobulin E (IgE) levels in serum and inflammatory cytokines in BALF using enzyme-linked immunosorbent assay (ELISA). Pathological changes in lung tissues, collagen deposition, and airway mucus secretion were observed by hematoxylin-eosin (HE), Masson, and periodic acid-Schiff (PAS) staining. TGF-β1/Smad3-related mRNA and protein levels in lung tissues were determined by Real-time fluorescent quantitative polymerase chain translation (Real-time PCR) and Western blot analysis. ResultCompared with the normal group, the model group showed increased total airway resistance (RL) and decreased dynamic compliance (Cdyn) (P<0.05, P<0.01), elevated serum IgE levels, increased inflammatory cell counts, and higher inflammatory cytokine levels in BALF (P<0.01). Additionally, there was significant inflammatory cell infiltration, collagen deposition, and mucus secretion in lung tissues. The levels of TGF-β1, α-smooth muscle actin (α-SMA), and Smad3 phosphorylation in lung tissues were significantly increased (P<0.01). Compared with the model group, the DEX group and high-dose YWHD group exhibited significantly reduced RL (P<0.01), improved lung dynamic compliance (P<0.05), and lower serum IgE levels, inflammatory cell counts, and inflammatory cytokine levels in BALF (P<0.05). Moreover, these treatments alleviated pathological damage in lung tissues and reduced the levels of TGF-β1, α-SMA, and Smad3 phosphorylation (P<0.01). ConclusionYWHD reduces airway inflammation, improves pathological damage, and mitigates airway remodeling in bronchial asthma rats, possibly by downregulating TGF-β1, α-SMA protein levels, and Smad3 phosphorylation.
7.Construction and validation of an in-hospital mortality risk prediction model for patients receiving VA-ECMO:a retrospective multi-center case-control study
Yue GE ; Jianwei LI ; Hongkai LIANG ; Liusheng HOU ; Liuer ZUO ; Zhen CHEN ; Jianhai LU ; Xin ZHAO ; Jingyi LIANG ; Lan PENG ; Jingna BAO ; Jiaxin DUAN ; Li LIU ; Keqing MAO ; Zhenhua ZENG ; Hongbin HU ; Zhongqing CHEN
Journal of Southern Medical University 2024;44(3):491-498
Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.
8.Proteomic analysis of differentially expressed proteins in gastrointestinal neuroendocrine tumors and their liver metastasis
Peng WANG ; Jianwei ZHANG ; Xu CHE
Chinese Journal of Oncology 2024;46(8):764-775
Objective:To investigate the differences of protein expressions in the primary tumors, adjacent tissues, and metastatic tumors of gastrointestinal neuroendocrine neoplasms.Methods:Nine patients with gastrointestinal neuroendocrine tumors (GI-NENs) with liver metastasis who underwent surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences from July 2015 to April 2019 were selected. The protein expressions of the primary tissues, liver metastatic tissues, and adjacent tissues were detected by the data independent acquisition (DIA) technology. P<0.05 and | log 2FC|>0.5 (FC as the difference multiple) were used as the criteria to identify the differentially expressed proteins in the primary tissues vs adjacent tissues, primary tissues vs liver metastatic tissues, primary tissues with different degrees of differentiation, and liver metastatic tissues with different degrees of differentiation. The differentially expressed proteins were investigated by volcano map analysis, cluster analysis, Gene Ontology (GO) function analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results:Compared with adjacent tissues, 85 proteins were downregulated and 42 proteins were upregulated in the primary tissues of gastric NENs. The differentially expressed proteins were mainly enriched in the biological processes related to the regulation of guanosidase triphosphate activity and the catabolism of deoxyribonucleoside monophosphate, the glycosaminoglycan biosynthesis chondroitin sulfate/dermatan sulfate, pantothenate, and CoA biosynthesis signaling pathways. 114 proteins were downregulated and 155 proteins were upregulated in the primary tissues of intestinal NENs. The differentially expressed proteins were mainly enriched in the biological processes related to glutathione metabolism and sulfur compound metabolism, collecting duct acid secretion, and taurine and hytaurine metabolism signaling pathways. Compared with the primary tissues of neuroendocrine cancers (NECs), 168 proteins were downregulated and 278 proteins were upregulated in G1-2 differentiation primary tissues. The differentially expressed proteins were significantly enriched in biological processes such as DNA metabolism and DNA replication, as well as replication, mismatch repair, and other pathways. Compared with the metastatic tissues of NECs, 95 proteins were downregulated and 97 proteins were upregulated in G1-2 differentiated metastases. The differentially expressed proteins were significantly enriched in the activity and catalytic activity of transcriptional coactivators, base excision repair, and protein efflux pathways. Compared with G1 differentiated primary tissues, 530 proteins were downregulated and 211 proteins were upregulated in G1 differentiated metastatic tissues. Compared with G2 differentiated primary lesions, 53 proteins were downregulated and 96 proteins were upregulated in G2 differentiated metastatic tissues. Compared with the primary lesions of NECs, 109 proteins were downregulated and 92 proteins were upregulated in the metastatic tissues of NECs. In G1 and G2 differentiated GI-NENs, there are many similar signal pathways enriched in differentially expressed proteins between primary lesions and metastases, while only one signal pathway enriched in differentially expressed proteins between primary and metastatic tissues of NECs is the same as that enriched in differentially expressed proteins between primary and metastatic tissues of GI-NENs, which is the drug metabolism signal pathway. The differentially expressed proteins in G1 differentiated primary and metastatic tissues were mainly expressed in cytoplasm (20.26%), mitochondria (18.67%), and nucleus (15.48%). The differentially expressed proteins in the primary and metastatic tissues of G2 differentiation were mainly expressed in the cytoplasm (20.24%), nucleus (18.25%), and cell membrane (15.08%). The differentially expressed proteins in the primary and metastatic tissues of NECs were mainly expressed in the nucleus (23.78%), cytoplasm (22.7%), and cell membrane (11.35%).Conclusion:The protein expressions of GI-NENs in the primary tissues, adjacent tissues, and metastatic tissues were significantly different in different sites and degrees of differentiation.
9.Construction and validation of an in-hospital mortality risk prediction model for patients receiving VA-ECMO:a retrospective multi-center case-control study
Yue GE ; Jianwei LI ; Hongkai LIANG ; Liusheng HOU ; Liuer ZUO ; Zhen CHEN ; Jianhai LU ; Xin ZHAO ; Jingyi LIANG ; Lan PENG ; Jingna BAO ; Jiaxin DUAN ; Li LIU ; Keqing MAO ; Zhenhua ZENG ; Hongbin HU ; Zhongqing CHEN
Journal of Southern Medical University 2024;44(3):491-498
Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.
10.Proteomic analysis of differentially expressed proteins in gastrointestinal neuroendocrine tumors and their liver metastasis
Peng WANG ; Jianwei ZHANG ; Xu CHE
Chinese Journal of Oncology 2024;46(8):764-775
Objective:To investigate the differences of protein expressions in the primary tumors, adjacent tissues, and metastatic tumors of gastrointestinal neuroendocrine neoplasms.Methods:Nine patients with gastrointestinal neuroendocrine tumors (GI-NENs) with liver metastasis who underwent surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences from July 2015 to April 2019 were selected. The protein expressions of the primary tissues, liver metastatic tissues, and adjacent tissues were detected by the data independent acquisition (DIA) technology. P<0.05 and | log 2FC|>0.5 (FC as the difference multiple) were used as the criteria to identify the differentially expressed proteins in the primary tissues vs adjacent tissues, primary tissues vs liver metastatic tissues, primary tissues with different degrees of differentiation, and liver metastatic tissues with different degrees of differentiation. The differentially expressed proteins were investigated by volcano map analysis, cluster analysis, Gene Ontology (GO) function analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results:Compared with adjacent tissues, 85 proteins were downregulated and 42 proteins were upregulated in the primary tissues of gastric NENs. The differentially expressed proteins were mainly enriched in the biological processes related to the regulation of guanosidase triphosphate activity and the catabolism of deoxyribonucleoside monophosphate, the glycosaminoglycan biosynthesis chondroitin sulfate/dermatan sulfate, pantothenate, and CoA biosynthesis signaling pathways. 114 proteins were downregulated and 155 proteins were upregulated in the primary tissues of intestinal NENs. The differentially expressed proteins were mainly enriched in the biological processes related to glutathione metabolism and sulfur compound metabolism, collecting duct acid secretion, and taurine and hytaurine metabolism signaling pathways. Compared with the primary tissues of neuroendocrine cancers (NECs), 168 proteins were downregulated and 278 proteins were upregulated in G1-2 differentiation primary tissues. The differentially expressed proteins were significantly enriched in biological processes such as DNA metabolism and DNA replication, as well as replication, mismatch repair, and other pathways. Compared with the metastatic tissues of NECs, 95 proteins were downregulated and 97 proteins were upregulated in G1-2 differentiated metastases. The differentially expressed proteins were significantly enriched in the activity and catalytic activity of transcriptional coactivators, base excision repair, and protein efflux pathways. Compared with G1 differentiated primary tissues, 530 proteins were downregulated and 211 proteins were upregulated in G1 differentiated metastatic tissues. Compared with G2 differentiated primary lesions, 53 proteins were downregulated and 96 proteins were upregulated in G2 differentiated metastatic tissues. Compared with the primary lesions of NECs, 109 proteins were downregulated and 92 proteins were upregulated in the metastatic tissues of NECs. In G1 and G2 differentiated GI-NENs, there are many similar signal pathways enriched in differentially expressed proteins between primary lesions and metastases, while only one signal pathway enriched in differentially expressed proteins between primary and metastatic tissues of NECs is the same as that enriched in differentially expressed proteins between primary and metastatic tissues of GI-NENs, which is the drug metabolism signal pathway. The differentially expressed proteins in G1 differentiated primary and metastatic tissues were mainly expressed in cytoplasm (20.26%), mitochondria (18.67%), and nucleus (15.48%). The differentially expressed proteins in the primary and metastatic tissues of G2 differentiation were mainly expressed in the cytoplasm (20.24%), nucleus (18.25%), and cell membrane (15.08%). The differentially expressed proteins in the primary and metastatic tissues of NECs were mainly expressed in the nucleus (23.78%), cytoplasm (22.7%), and cell membrane (11.35%).Conclusion:The protein expressions of GI-NENs in the primary tissues, adjacent tissues, and metastatic tissues were significantly different in different sites and degrees of differentiation.

Result Analysis
Print
Save
E-mail