1.Establishment of an immune-related LncRNA based prognostic risk assessment model for pancreatic cancer according to TCGA database
Zhenchao GAO ; Yiqun SONG ; Xinlong CHEN ; Ze'en ZHU ; Zheng WANG ; Weikun QIAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(4):663-670
Objective To screen immune-related long non-coding RNAs(LncRNAs)in the TCGA database pancreatic cancer dataset and construct a prognostic risk assessment model with immune-related LncRNAs to explore prognosis-related potential molecular mechanisms.Methods RNA-seq data of 171 pancreatic cancer samples and corresponding clinical information were obtained by The Cancer Genome Atlas(TCGA)database,and two classical immune-related gene datasets(GO0006955/IMMUNE RESPONSE and GO0002376/IMMUNE SYSTERM PROCESS)and gene annotation information were used to identify immune-related LncRNAs.The immune-related LncRNAs associated with pancreatic cancer prognosis were used for univariate and multivariate Cox analyses to establish a model for the assessment of pancreatic cancer prognostic risk based on immune-associated LncRNAs.This risk model was used for survival analysis,clinical correlation analysis,immune cell infiltration analysis,pathway enrichment analysis,and prognostic column line plot modeling.Results We screened 119 immune-related LncRNAs in pancreatic cancer,and five immune-related LncRNAs(AC064836.3,LINC00941,ZNF236-DT,TMEM161B-AS1 and AC068580.2)were identified for the development of pancreatic cancer prognostic risk assessment model.According to the prognostic risk assessment model,pancreatic cancer patients were divided into low-risk group(n=86)and high-risk group(n=85).Compared with the low-risk group,the high-risk group showed a significant negative enrichment trend for immune-related signaling pathways,the 5-year overall survival of pancreatic cancer patients was significantly increased in the low-risk group compared with the high-risk group.The expression of low-risk immune-related LncRNAs(AC064836.3,ZNF236-DT and TMEM161B-AS1)gradually decreased with increasing clinical stage of pancreatic cancer patients.Patient age(P=0.031,risk ratio and 95%CI:1.025/1.002-1.048)and prognostic risk score(P<0.001,risk ratio and 95% confidence interval 1.801/1.465-2.215)could be used as independent prognostic risk factors for overall survival in pancreatic cancer.In addition,the prognostic risk assessment model had better predictive efficiency(area under the curve=0.695)compared with the disease predictive ability of common clinical characteristics.Steroid biosynthesis,pentose phosphate pathway,intercellular linkage,cytoskeletal rearrangement and other pathways related to energy metabolism and invasive migration of pancreatic cancer cells were significantly activated in the high-risk group.Meanwhile,pancreatic cancer patients in the high-risk group had lower levels of naive B cells,plasma cells and neutrophils with anti-tumor activity,but their macrophage infiltration levels were significantly higher than those in the low-risk group.Conclusion The prognostic risk assessment model constructed based on five immune-related LncRNAs can effectively predict the survival status,clinical characteristics,molecular pathways,and immune cell infiltration differences of pancreatic cancer patients.Meanwhile,relying on this model,the prognosis of pancreatic cancer patients can be prospectively predicted,which enhances the usefulness of this risk prediction model.
2.Establishment of an immune-related LncRNA based prognostic risk assessment model for pancreatic cancer according to TCGA database
Zhenchao GAO ; Yiqun SONG ; Xinlong CHEN ; Ze'en ZHU ; Zheng WANG ; Weikun QIAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(4):663-670
Objective To screen immune-related long non-coding RNAs(LncRNAs)in the TCGA database pancreatic cancer dataset and construct a prognostic risk assessment model with immune-related LncRNAs to explore prognosis-related potential molecular mechanisms.Methods RNA-seq data of 171 pancreatic cancer samples and corresponding clinical information were obtained by The Cancer Genome Atlas(TCGA)database,and two classical immune-related gene datasets(GO0006955/IMMUNE RESPONSE and GO0002376/IMMUNE SYSTERM PROCESS)and gene annotation information were used to identify immune-related LncRNAs.The immune-related LncRNAs associated with pancreatic cancer prognosis were used for univariate and multivariate Cox analyses to establish a model for the assessment of pancreatic cancer prognostic risk based on immune-associated LncRNAs.This risk model was used for survival analysis,clinical correlation analysis,immune cell infiltration analysis,pathway enrichment analysis,and prognostic column line plot modeling.Results We screened 119 immune-related LncRNAs in pancreatic cancer,and five immune-related LncRNAs(AC064836.3,LINC00941,ZNF236-DT,TMEM161B-AS1 and AC068580.2)were identified for the development of pancreatic cancer prognostic risk assessment model.According to the prognostic risk assessment model,pancreatic cancer patients were divided into low-risk group(n=86)and high-risk group(n=85).Compared with the low-risk group,the high-risk group showed a significant negative enrichment trend for immune-related signaling pathways,the 5-year overall survival of pancreatic cancer patients was significantly increased in the low-risk group compared with the high-risk group.The expression of low-risk immune-related LncRNAs(AC064836.3,ZNF236-DT and TMEM161B-AS1)gradually decreased with increasing clinical stage of pancreatic cancer patients.Patient age(P=0.031,risk ratio and 95%CI:1.025/1.002-1.048)and prognostic risk score(P<0.001,risk ratio and 95% confidence interval 1.801/1.465-2.215)could be used as independent prognostic risk factors for overall survival in pancreatic cancer.In addition,the prognostic risk assessment model had better predictive efficiency(area under the curve=0.695)compared with the disease predictive ability of common clinical characteristics.Steroid biosynthesis,pentose phosphate pathway,intercellular linkage,cytoskeletal rearrangement and other pathways related to energy metabolism and invasive migration of pancreatic cancer cells were significantly activated in the high-risk group.Meanwhile,pancreatic cancer patients in the high-risk group had lower levels of naive B cells,plasma cells and neutrophils with anti-tumor activity,but their macrophage infiltration levels were significantly higher than those in the low-risk group.Conclusion The prognostic risk assessment model constructed based on five immune-related LncRNAs can effectively predict the survival status,clinical characteristics,molecular pathways,and immune cell infiltration differences of pancreatic cancer patients.Meanwhile,relying on this model,the prognosis of pancreatic cancer patients can be prospectively predicted,which enhances the usefulness of this risk prediction model.
3.Interpretation of REDISCOVER international guidelines on the perioperative care of surgical patients with borderline-resectable and locally advanced pancreatic cancer(2024)
Jiahui ZENG ; Kongyuan WEI ; Weikun QIAN ; Zheng WANG ; Liang HAN
Journal of Clinical Hepatology 2024;40(11):2183-2190
The REDISCOVER international guidelines on the perioperative care of surgical patients with borderline-resectable and locally advanced pancreatic cancer were released in July 2024,and based on the existing clinical challenges,the guidelines provide important recommendations for the diagnosis,staging,and surgical treatment of borderline-resectable and locally advanced pancreatic cancer from an evidence-based perspective.This article gives an interpretation of the guidelines,in order to better guide clinical practice.
4.Huaier alleviates acute pancreatitis in mice by reducing ROS-induced pyroptosis in acinar cells
Mengyuan GONG ; Bo ZHANG ; Ze’en ZHU ; Qingyong MA ; Zheng WU ; Zheng WANG ; Weikun QIAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):183-191
【Objective】 To investigate the therapeutic effect of Huaier on acute pancreatitis (AP) and its potential mechanism. 【Methods】 A mouse model of cerulean-induced AP was used to verify the therapeutic effect of Huaier in vivo. HE staining and immunohistochemical staining were used to evaluate the histopathological changes of the pancreas, and transmission electron microscopy was used to observe the pyroptosis morphology of the pancreas. In vitro, 266-6 cell line was used as the experimental carrier to verify the protective effect of Huaier on acinar cells. Electron microscopy and Western blotting were used to evaluate the pyroptosis level of acinar cells, and ROS fluorescence probe was used to detect the oxidative stress state of acinar cells. 【Results】 Huaier significantly alleviated the severity of AP in mice. HE staining of pancreas showed that necrosis and inflammatory cell infiltration were reduced, and the level of serum amylase was decreased. Immunohistochemical staining and Western blotting showed that Huaier effectively inhibited the expressions of pyroptosis-related molecules such as NLRP3 and GSDMD in pancreatic tissue. Electron microscopy showed that Huaier could reduce the pyroptosis level of pancreatic acinar cells under inflammatory state. In addition, the level of ROS in acinar cells was significantly reduced after the intervention of Huaier, and ROS-mediated pyroptosis of acinar cells could be effectively inhibited by Huaier. 【Conclusion】 Huaier can effectively reduce the severity of AP by inhibiting ROS-mediated pyroptosis of acinar cells.
5.Clinical characteristics and treatment mode changes of chronic pancreatitis: a 10-year single center study
Wanzhen WEI ; Wanxing DUAN ; Jinpeng ZHAO ; Shuai WU ; Weikun QIAN ; Zheng WU ; Xue YANG ; Zheng WANG
Chinese Journal of Digestive Surgery 2024;23(5):726-732
Objective:To investigate the clinical characteristics and treatment mode changes of chronic pancreatitis (CP).Methods:The retrospective and descriptive study was conducted. The clinical data of 805 patients with CP who were admitted to the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2022 were collected. There were 575 males and 230 females, aged 52(range, 10-87)years. Observation indicators: (1)demographic characteristics; (2)distribution of admission departments, hospitalization and treatment status. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distri-bution were represented as M(range). Count data were expressed as absolute numbers and percentages. The chi-square goodness-of-fit test was used for consistent between expected frequency and empirical distribution. Results:(1)Demographic characteristics. Of the 805 patients, there were 435 cases and 370 cases diagnosed as CP according to the primary and secondary diagnostic criteria, respec-tively, and the age of initial presentation of 805 patients was 52(range, 10-87)years. Among male and female patients, there was 1 and 0 case in the age group of 0-10 years, there were 16 and 14 cases in 11-20 years, 45 and 26 cases in 21-30 years, 82 and 30 cases in 31-40 years, 122 and 39 cases in 41-50 years, 157 and 51 cases in 51-60 years, 119 and 46 cases in 61-70 years, 31 and 21 cases in 71-80 years, 2 and 3 cases in 81-90 years, respectively. Patients aged 0-14, 15-34, 35-64, and ≥65 years were 0, 6, 28, and 9 for 2013, 1, 21, 34, and 10 for 2014, 1, 8, 38, and 7 for 2015, 0, 7, 52, and 10 for 2016, 0, 11, 35 and 9 for 2017, 1, 15, 72 and 23 for 2018, 0, 9, 55 and 11 for 2019, 2, 19, 58 and 16 for 2020, 0,20, 79 and 18 for 2021, 0, 25, 73 and 22 for 2022, respectively. Of the 805 patients, cases from Shaanxi Province, Gansu Province and other regions were 702, 48 and 55, respectively. There are 802 Han and 3 Hui patients, respectively, and the married, unmarried, divorced, and widowed patients were 732, 64, 7, and 2, respectively. Cases with blood type information was 682, with the distribution of blood types as 26.10%(178/682) of type A, 34.46%(235/682)of type B, 9.97%(68/682) of type AB, 29.47%(201/682)of type O, showing no significant difference compared to the distribu-tion of blood types in population of Shaanxi Province in 2022 (28.43% of type A, 30.50% of type B, 9.83% of type AB, and 30.50% of type O) ( χ2=0.50, P>0.05). (2)Distribution of departments, hospita-lization, and treatment. Of the 805 patients, cases admitted to the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments (Department of Geriatric Surgery, Infectious Diseases and General Surgery) were 594, 121 and 90, respectively. Cases of the number of hospitalizations in the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments were 771, 121 and 94, respectively. One patient might have been admitted for multiple times. The duration of hospital of stay of 805 patients was 11(rang, 1-67)days. The duration of hospital stay of patients admitted to the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments were 16(range, 2-48)days, 11(range, 5-19)days and 24(range, 12-35)days for 2013, 18(range, 2-63)days, 10(range, 3-29)days and 14(range, 7-30)days for 2014, 9(range, 1-35)days, 11(range, 2-16)days and 10(range, 5-33)days for 2015, 10(range, 1-55)days, 9(range, 4-16)days and 16(range, 4-27)days for 2016, 9(range, 2-38)days, 10(range, 4-20)days and 11(range, 5-27)days for 2017, 12(range, 3-46)days, 11(range, 2-26)days and 13(range, 7-27)days for 2018, 11(range, 1-33)days, 9(range, 3-23)days and 14(range, 4-17)days for 2019, 11(range, 1-67)days, 7(range, 1-23)days, and 16(range, 4-27)days for 2020, 10(range, 1-35)days, 8(range, 1-32)days and 14(range, 1-29)days for 2021, 9(range, 1-42)days, 12(range, 3-17)days and 11(range, 1-22)days for 2022. Of the 805 patients, cases receiving treatment as surgical treatment, pancreas extracorporeal shock wave lithotripsy (P-ESWL), endoscopic treatment and other treatments were 258, 117, 194 and 236, respectively. A total of 260 surgeries were performed on 258 patients receiving surgical treatment, and there were 236 cases receiving surgical treatment as the first choice, and 22 cases undergoing surgery after failed of other treatments. The surgical procedures included pancreaticoduodenectomy in 79 cases, distal pancreatectomy (with or without splenectomy, Peustow procedure) in 35 cases, partial pancreatectomy with pancreatic duct incision and stone removal and pancreaticojejunostomy in 77 cases, simple pancreatic duct incision and pancreaticojejunostomy in 58 cases, internal drainage for pancreatic pseudocysts in 4 cases, and drainage for removal of pancreatic necrotic tissue in 7 cases. There were 58 patients with post-operative complications, including 9 cases of bleeding, 19 cases of infection, 2 cases of gastric paresis, 21 cases pancreatic fistula, and 7 cases of intestinal leakage. Cases with postoperative complications were recovered and discharged after symptomatic treatment. Of the 117 patients receiving P-ESWL, the times of treatment per patient was 1.3±0.7, and a total of 154 times of P-ESWL were performed. There were 89 patients receiving one time of P-ESWL, and 28 patients receiving ≥2 times of P-ESWL. Of the 194 patients receiving endoscopic treatment, the times of treatment per patient was 1.2±0.6, and a total of 238 times of endoscopic treatment were performed. There were 103 cases receiving stent placement, 43 cases receiving nasopancreatic/nasobiliary drainage, 7 cases receiving pancreatic duct balloon dilation, 71 cases receiving pancreatic stone removal, and 58 cases receiving duodenal papilla sphincterotomy. There were 168 patients receiving one time of endoscopic treatment, and 26 patients receiving ≥2 times of endoscopic treatment.There was no postoperative complica-tions reported. Conclusions:The proportion of males in CP patients is relatively high, and the proportion gradually increases with age of 51-60 years. There is no significant difference in the distribution of blood types among CP patients and the population of Shaanxi Province. The proportion of minimally invasive treatment (extracorporeal shock wave lithotripsy and endoscopic therapy) in CP treatment is on the rise, and the duration of hospital stay for patients is on the decline.
6.RASAL2 promotes pancreatic cancer vasculogenic mimicry through AKT/β-catenin pathway
Bao YANG ; Feibai MA ; Weikun QIAN ; Cancan ZHOU ; Zheng WANG ; Yangyang YUE
Tumor 2024;44(11):1104-1115
Objective:To investigate the role of RASAL2 in vasculogenic mimicry in pancreatic cancer cells and to preliminarily explore the potential molecular mechanisms involved.Methods:The clinical proteomic tumor analysis consortium(CPTAC)database was used to analyze the expression of RASAL2 in pancreatic cancer,and immunohistochemical method was used to detect the expression of RASAL2,β-catenin and Vimentin in pancreatic cancer and adjacent tissues.In the pancreatic cancer cell line,after lentivirus infection knockdown and overexpression of RASAL2,transcriptome sequencing was performed on pancreatic cancer cells silencing RASAL2 expression,and vasculogenic mimicry experiment was used to detect the effect of RASAL2 on angiogenesis of pancreatic cancer cells;The molecular mechanism of RASAL2 promoting vasculogenic mimicry in pancreatic cancer was studied by real-time fluorescent quantitative PCR and Western blotting detection.Results:The analysis results of CPTAC database showed that the expression level of RASAL2 protein in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue.Immunohistochemical test results showed that the expression of RASAL2 in pancreatic cancer tissue was up-regulated,and the expression of β-catenin and Vimentin in pancreatic cancer tissue was also significantly up-regulated.The second-generation transcriptome sequencing results showed that RASAL2 may be involved in the biological behavior of intercellular connections and adhesion.After knocking down RASAL2 expression in pancreatic cancer cell PANC-1,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins decreased,and the formation of vasculogenic mimicry structure was inhibited;After overexpression of RASAL2 in pancreatic cancer cell BxPC-3,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins increased,promoting the formation of vasculogenic mimicry.Conclusion:The effect of RASAL2 on vasculogenic mimicry in pancreatic cancer cells is related to AKT/β-catenin signaling pathway.
7.RASAL2 promotes pancreatic cancer vasculogenic mimicry through AKT/β-catenin pathway
Bao YANG ; Feibai MA ; Weikun QIAN ; Cancan ZHOU ; Zheng WANG ; Yangyang YUE
Tumor 2024;44(11):1104-1115
Objective:To investigate the role of RASAL2 in vasculogenic mimicry in pancreatic cancer cells and to preliminarily explore the potential molecular mechanisms involved.Methods:The clinical proteomic tumor analysis consortium(CPTAC)database was used to analyze the expression of RASAL2 in pancreatic cancer,and immunohistochemical method was used to detect the expression of RASAL2,β-catenin and Vimentin in pancreatic cancer and adjacent tissues.In the pancreatic cancer cell line,after lentivirus infection knockdown and overexpression of RASAL2,transcriptome sequencing was performed on pancreatic cancer cells silencing RASAL2 expression,and vasculogenic mimicry experiment was used to detect the effect of RASAL2 on angiogenesis of pancreatic cancer cells;The molecular mechanism of RASAL2 promoting vasculogenic mimicry in pancreatic cancer was studied by real-time fluorescent quantitative PCR and Western blotting detection.Results:The analysis results of CPTAC database showed that the expression level of RASAL2 protein in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue.Immunohistochemical test results showed that the expression of RASAL2 in pancreatic cancer tissue was up-regulated,and the expression of β-catenin and Vimentin in pancreatic cancer tissue was also significantly up-regulated.The second-generation transcriptome sequencing results showed that RASAL2 may be involved in the biological behavior of intercellular connections and adhesion.After knocking down RASAL2 expression in pancreatic cancer cell PANC-1,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins decreased,and the formation of vasculogenic mimicry structure was inhibited;After overexpression of RASAL2 in pancreatic cancer cell BxPC-3,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins increased,promoting the formation of vasculogenic mimicry.Conclusion:The effect of RASAL2 on vasculogenic mimicry in pancreatic cancer cells is related to AKT/β-catenin signaling pathway.
8.Bioinformatics analysis of survival-related genes in pancreatic cancer based on GEO and TCGA database
Mengyuan GONG ; Qiqi WANG ; Zeen ZHU ; Zheng WU ; Zheng WANG ; Weikun QIAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(5):717-724
【Objective】 Based on Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database, survival analysis was used to screen the key prognostic genes involved of pancreatic cancer patients. 【Methods】 Two pancreatic cancer gene chips (Microarray) from the GEO database and transcriptome sequencing (RNA-seq) from the TCGA database were used to filter the survival-related genes using Kaplan-Meier (KM) analysis and Cox risk model, and the target genes were intersected. Prognosis-associated genes were screened first and then pathway enrichment analysis or immune-enrichment analysis was performed based on these genes to find out their potential molecular mechanisms in regulating pancreatic cancer. 【Results】 In this study, five survival-related genes (i.e., CDO1, DCBLD2, FAM83A, ITGA3 and SLC16A3) were screened out. Multifactorial Cox regression analysis and clinical correlation analysis showed that high CDO1 expression was a protective factor for pancreatic cancer prognosis, and its antitumor effect was associated with its role in inhibiting the malignant biological behavior of pancreatic cancer cells and promoting the infiltration of immune killer cells in pancreatic cancer. 【Conclusion】 This study suggests that CDO1 is a potential tumor suppress gene of pancreatic cancer, and the tumor inhibition effect of CDO1 may be related to its role in remodeling the immune microenvironment of pancreatic cancer.

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