1.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
2.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
3.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
4.Effects of methionine restriction on the proliferation and the pentose phosphate pathway of lung adenocarcinoma cells
LI Yuyu ; LI Shiri ; LI Zhiying ; ZHAO Zhenggang ; LI Fanghong ; ZHAO Zijian ; ZHOU Sujin
Chinese Journal of Cancer Biotherapy 2025;31(8):799-805
[摘 要] 目的:探讨甲硫氨酸限制对肺腺癌(LUAD)细胞增殖、凋亡及磷酸戊糖途径的影响。方法:将H1299、A549细胞分为Met+组和Met−组,分别用含100 μmol/L或不含甲硫氨酸的培养基连续培养4 d,采用细胞计数法评估甲硫氨酸处理对H1299和A549细胞增殖的影响,PI染色法检测细胞周期分布,Annexin Ⅴ-PE/7AAD标记细胞凋亡,利用DCFH-DA探针检测细胞内ROS水平,WST-8法和DTNB法分别测定细胞内NADPH与GSH含量;通过癌症基因组图谱(TCGA)数据库分析葡萄糖-6-磷酸脱氢酶(G6PD)和6-磷酸葡萄糖酸脱氢酶(6PGD)表达与甲硫氨酸代谢通路的关系;采用WB法检测甲硫氨酸处理及回补甲硫氨酸下游代谢产物S-腺苷甲硫氨酸(SAM)对LUAD细胞中磷酸戊糖途径关键酶G6PD和6PGD表达的影响。结果:甲硫氨酸限制显著抑制H1299和A549细胞增殖(均P < 0.01),将细胞周期阻滞于G2/M期(均P < 0.05),显著升高细胞内总ROS水平(均P < 0.001)并促进细胞凋亡(均P < 0.001);同时,甲硫氨酸限制显著降低了细胞内NADPH和GSH水平(均P < 0.01),抑制DNA合成(均P < 0.01)。分析TCAG数据发现,G6PD和6PGD表达水平与甲硫氨酸代谢通路呈正相关(均P < 0.001),甲硫氨酸限制下调G6PD和6PGD蛋白表达(均P < 0.01),而回补SAM可部分逆转甲硫氨酸限制对G6PD和6PGD的表达的抑制(均P < 0.01),提示甲硫氨酸通过SAM合成调控磷酸戊糖途径。结论:甲硫氨酸限制通过抑制磷酸戊糖途径抑制LUAD细胞增殖,为甲硫氨酸限制疗法治疗LUAD提供实验依据。
5.Status quo of cognitive frailty in community elderly patients with chronic obstructive pulmonary disease and its association with sleep quality, anxiety and depression
Zongquan ZHAO ; Hao ZHANG ; Jun SUN ; Yajuan ZHANG ; Xiangfan TIAN ; Xiaohong WANG ; Zhenyuan TANG ; Zhiying ZHANG
Journal of Public Health and Preventive Medicine 2025;36(5):71-75
Objective To analyze the status quo of cognitive frailty (CF) in community elderly patients with chronic obstructive pulmonary disease (COPD) and its correlation with sleep quality, anxiety and depression. Methods Elderly patients with COPD receiving health management in the center were selected from July 2023 to June 2024. The general data of patients were collected and Mini-Mental State Examination (MMSE), Fried Frailty Phenotype (FP), Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) were used for investigation, and the above scores were analyzed. All patients were divided into CF group (n=129) and non-CF group (n=319) according to MMSE score and FP score. Univariate and multivariate logistic analyses were used to analyze the influencing factors of CF in elderly COPD patients. Results Pearson correlation analysis showed that MMSE score was significantly negatively correlated with PSQI score and HADS score in elderly COPD patients (P<0.05), and FP score was significantly positively correlated with PSQI score and HADS score (P<0.05). After logistic regression analysis, it was found that education level, marital status and sleep time were protective factors of CF in elderly COPD patients (P<0.05), and PSQI score and HADS score were risk factors of CF in elderly patients with COPD (P<0.05). Conclusion CF in community elderly COPD patients is related to sleep quality, sleep duration and anxiety and depression. It is necessary to take clinical measures to improve the sleep quality and psychological status, so as to avoid or slow down the occurrence of CF.
6.Predictive value of preoperative combined detection of NLR and PTAR for early abdominal infection after liver transplantation
Huabin PENG ; Ying LIU ; Fei HOU ; Shuang ZHAO ; Yizhi ZHANG ; Tingting CUI ; Zhiying HE ; Jingyi LIU ; Haofeng XIONG ; Liying SUN
Organ Transplantation 2025;16(6):931-943
Objective To investigate the predictive value of preoperative combined detection of neutrophil-to-lymphocyte ratio (NLR) and prothrombin time-international normalized ratio to albumin ratio (PTAR) for early abdominal infection after liver transplantation. Methods Clinical data of 287 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital, Affiliated to Capital Medical University, from January 2020 to April 2024 were retrospectively analyzed. The patients were divided into infection group (n=60) and non-infection group (n=227) based on whether abdominal infection occurred within 30 days after surgery. The distribution characteristics of pathogens and infection time in infected patients were analyzed. Spearman correlation analysis was used to assess the correlation between NLR, PTAR, Child-Pugh score and preoperative model for end-stage liver disease (MELD) score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for abdominal infection. Receiver operating characteristic (ROC) curves were plotted for NLR, PTAR, and the combined prediction model to evaluate their predictive efficacy for abdominal infection after liver transplantation. Based on the cutoff value of the combined model, recipients were divided into low-risk and high-risk groups, and Kaplan-Meier analysis was used to compare the cumulative incidence of abdominal infection within 30 days after surgery between the two groups. Results Among the 287 recipients who underwent liver transplantation, 60 developed bacterial or fungal abdominal infections postoperatively. A total of 86 strains were isolated from infected patients, with Gram-negative bacteria accounting for 58%, Gram-positive bacteria for 36%, and fungi for 5%. Preoperative NLR and PTAR were positively correlated with Child-Pugh and MELD scores (all 1 > r > 0, P < 0.05). Logistic regression analysis showed that preoperative NLR, preoperative PTAR, postoperative ICU stay duration and postoperative biliary leakage were risk factors for abdominal infection within 30 days after surgery. The area under the curve (AUC) for NLR, PTAR, Child-Pugh score and MELD score were 0.771, 0.735, 0.650 and 0.741, respectively. The AUC for the combined NLR and PTAR prediction model was 0.824 (95% confidence interval: 0.763-0.885, P < 0.001), with a cutoff value of 0.168. Kaplan-Meier analysis showed that the cumulative incidence of abdominal infection within 30 days after surgery was lower in the low-risk group than in the high-risk group, with statistically significant difference (P < 0.001). Conclusions Preoperative NLR and PTAR are independent risk factors for abdominal infection within 30 days after liver transplantation. The combined prediction model of NLR and PTAR may effectively identify high-risk recipients for early abdominal infection after liver transplantation, providing basis for early intervention.
7.Analysis of factors influencing postoperative delirium in patients with Stanford Type A aortic dissection
Jun ZHAO ; Shan ZHANG ; Hongxia ZHAO ; Yuan TIAN ; Zhiying LI ; Ying WU
Chinese Journal of Modern Nursing 2024;30(28):3873-3879
Objective:To explore the incidence of postoperative delirium (POD) in patients with Stanford Type A aortic dissection and analyze the influencing factors and predictive efficacy of these factors for POD.Methods:Totally 237 patients with Stanford Type A aortic dissection who were treated at Beijing Anzhen Hospital, Capital Medical University, from May 2020 to February 2021 were selected by convenience sampling. Data were collected using a general information questionnaire, the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), the Pittsburgh Sleep Quality Index (PSQI), the State-Trait Anxiety Inventory (STAI), and the Chinese version of the Critical Care Pain Observation Tool (CPOT). Logistic regression analysis was employed to identify factors influencing POD, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of each influencing factor and determine the optimal cutoff values.Results:A total of 237 questionnaires were distributed, with 232 valid questionnaires returned, yielding a recovery rate of 97.89% (232/237). Among the 232 patients, 37 developed delirium, resulting in an incidence rate of 15.95% (37/232). Logistic regression analysis revealed that carotid artery involvement, preoperative anxiety scores, postoperative pain scores, and length of ICU stay were influencing factors for POD in patients with Stanford Type A aortic dissection ( P<0.05). ROC curve analysis indicated that the area under the curve ( AUC) values for preoperative anxiety scores, postoperative pain scores, length of ICU stay, and carotid artery involvement in predicting POD were 0.924, 0.927, 0.954, and 0.718, respectively. Conclusions:The incidence of POD in patients with Stanford Type A aortic dissection is relatively high. Preoperative anxiety, postoperative pain, length of ICU stay, and carotid artery involvement are key factors influencing the occurrence of POD in these patients.
8.The correlation analysis between nutritional risk screening scores and the levels of malnutrition in primary hospitals
Xia ZHAO ; Zhiying TAO ; Liping SUN
China Modern Doctor 2024;62(27):61-63
Objective To analyze the correlation between the scores obtained according to nutritional risk screening 2002(NRS 2002)and malnutrition level diagnosed according to global leadership initiative on malnutrition(GLIM)in district level primary hospital.Methods A retrospective study was conducted involving 361 patients with positive nutritional risk screening(NRS 2002 score ≥3 points)admitted to General Hospital Medical Communities of Shaoxing Second Hospital from November 2023 to February 2024.The patients were diagnosed for malnutrition according to GLIM criteria,and those identified with malnutrition were further evaluated for the severity of malnutrition(moderate malnutrition or severe malnutrition).Statistical methods were employed to analyze the correlation between nutritional risk screening scores and the severity of malnutrition.Results Among 361 patients with positive nutritional risk screening,179 cases were diagnosed with no malnutrition,140 cases with moderate malnutrition,and 42 cases with severe malnutrition.Analysis using Kendall's tau-b coefficient revealed a strong positive correlation between nutritional risk screening(NRS 2002)scores and malnutrition levels by GLIM criteria(Kendall's tau-b>0.6,P<0.0001).The occurrence of malnutrition differed significantly between age groups(<70 years old and ≥70 years old)(P<0.05),there is no statistically significant difference in the incidence of malnutrition between different gender groups(P>0.05).Conclusion There was a strong positive correlation between higher nutritional risk screening scores(according to NRS 2002)and higher levels of malnutrition(according to GLIM)in the primary hospital.The prevalence of malnutrition was not related to gender,but those aged ≥ 70 years old had a higher prevalence of malnutrition compared to those aged<70 years old.
9.Predictive value of a new radiotherapy plan evaluation tool for bladder toxicity in cervical cancer
Qingxiao LIU ; Yuexiang ZHU ; Long TIAN ; Songlin YANG ; Zheng WANG ; Yusen ZHAO ; Zhiying REN ; Maoye CHANG
Chinese Journal of Radiological Health 2024;33(2):189-194
Objective To evaluate the predictive value of a dose-surface histogram (DSH) for radiation cystitis (RC) in patients with cervical cancer. Methods We retrospectively included 190 patients with cervical cancer who underwent image-guided radiotherapy (IGRT) from the HIS system of The First Affiliated Hospital of Hebei North University from May 2013 to May 2023. The patients were divided into test group (n = 100) and control group (n = 90). The dose distribution in the bladder was evaluated by using a DSH for the test group and using a dose-volume histogram (DVH) for the control group. Receiver operating characteristic curves were used to evaluate the predictive value of DSH for RC in comparison with DVH. Results There were no significant differences in baseline data and RC incidence between the two groups (all P>0.05). All evaluation indicators were significantly different between DSH and DVH (all P<0.05). The predictive value of S45 and V45 for the incidence of grade-I, -II, and -III RC was low (all P<0.05). The predictive value of S50 and V50 for the incidence of grade-I, -II, and -III RC was moderate (all P<0.05). S55−S57 and V55−V57 showed high value for predicting the incidence of grade-I, -II, and -III RC (all P<0.05). Conclusion DSH shows basically the same predictive value for the incidence of RC caused by IGRT in cervical cancer as DVH, which is expected to become a new tool for evaluating radiotherapy plans.
10.Intra-and peri-tumoral radiomics model for predicting the response to concurrent chemoradiotherapy in cervical squamous cell carcinoma based on dynamic contrast-enhanced MRI
Yaying SU ; Dan ZHAO ; Zhiying PANG ; Fei YANG ; Shujun CUI
Journal of Practical Radiology 2024;40(3):411-416
Objective To investigate the correlation between intra-and peri-tumoral radiomics features and the response to con-current chemoradiotherapy(CCRT)in cervical squamous cell carcinoma,and to explore the difference of predictive performance between 2D and 3D radiomics models.Methods The imaging data of 132 patients were analyzed retrospectively and randomly divided into training set(n=92)and validation set(n=40).Radiomics features were extracted based on the dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),the correlation analysis and least absolute shrinkage and selection operator(LASSO)algorithm were used for dimensionality reduction and screening,then the radiomics score was calculated and the logistic model was constructed.The receiver operating characteristic(ROC)curve,internal validation of Bootstrap and Brier score were used to evaluate the discrimina-tion and calibration of the model,and the improvement in predictive performance of 3D model compared with 2D model was evaluated by the integrated discrimination improvement(IDI).Results In the training set,the ROC curve showed that the area under the curve(AUC)of the models(2D-intratumoral,3D-intratumoral,3D-peritumoral,3D-combined)ranged from 0.774 to 0.893.The internal validation of Bootstrap showed the AUC were 0.772,0.860,0.847 and 0.888,respectively,while in the validation set,the AUC were 0.757,0.849,0.824 and 0.887,respectively.The Brier scores indicated that the models were well calibrated.In the training set and the validation set,the IDI values were 0.155 and 0.179,respectively,and the differences were statistically significant(P<0.05).Conclusion The radiomics analysis based on the tumor volume can fully explore the tumor heterogeneity.The intra-and peri-tumoral radiomics combined model shows the best predictive performance,which is important to assist clinicians in developing individualized therapies.


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