ABSTRACT
Objective:To analyze the expression of cell division cycle associated protein 5 (CDCA5) in pancreatic cancer tissues and its correlation with prognosis based on the bioinformatics.Methods:The RNA sequencing data (HTSeq-FPKM) and corresponding clinical information of 168 pancreatic cancer samples from January to December 2021 were downloaded from the Cancer Genome Atlas (TCGA) database, and the data of 179 pancreatic patients from January to December 2021 were downloaded from the GEPIA2 database, and 171 normal pancreatic tissues from TCGA and GTEx databases were simultaneously integrated. The relative expression level of CDCA5 mRNA in pancreatic cancer patients in GEPIA2 database and its relationship with overall survival (OS) and disease-free survival (DFS) were explored. Combined with the clinical data of the patients, univariate and multivariate Cox regression model analysis was used to analyze the factors influencing the OS of pancreatic cancer patients. Gene set enrichment analysis (GSEA) was performed to investigate the possibly involved signal pathways of CDCA5 in pancreatic cancer.Results:In the GEPIA2 database, the relative expression level of CDCA5 mRNA in pancreatic cancer tissues was higher than that in normal pancreatic tissues, and the difference was statistically significant ( P < 0.05). The pancreatic cancer patients were divided into the high CDCA5 mRNA expression group (89 cases) and the low CDCA5 mRNA expression group (89 cases) according to the median of relative expression level of CDCA5 mRNA (the case equal to the median value was not subgrouped). Survival analysis showed that patients with high CDCA5 mRNA expression had shorter OS ( P = 0.024) and DFS ( P = 0.025) compared with those with low CDCA5 mRNA expression. Multivariate Cox analysis showed that in TCGA database, N staging ( HR = 2.15, 95% CI 1.24-3.72, P = 0.006) and CDCA5 expression ( HR = 1.71, 95% CI 1.23-2.38, P = 0.001) were independent influencing factors of OS for pancreatic cancer patients. The results of GSEA enrichment analysis indicated that high CDCA5 mRNA expression was enriched in 13 biological pathways [all P < 0.05, false discovery rate (FDR) < 0.005] including cell cycle, DNA replication, homologous recombination, pyrimidine metabolism, mismatch repair, pentose phosphate pathway, glycolysis gluconeogenesis and p53. The expression of CDCA5 mRNA was positively correlated with the expressions of HK2, PKM, PGK1, ALDOA, EN01 and LDHA (all P < 0.05). Conclusions:CDCA5 is highly expressed in pancreatic cancer tissues and is associated with poor prognosis of patients, and it can be used as a prognostic marker for pancreatic cancer.
ABSTRACT
Objective:To explore the early diagnostic value of thrombus molecular markers in thrombosis ofpatients with malignant tumors and to evaluate their risk factors.Methods:Diagnostic research.A total of 1366 patients (including lung cancer, breast cancer and colorectal cancer,) were randomly selected in the Red Flag Hospital of Mudanjiang Medical College and Mudanjiang Cancer Hospitalfrom September 2009 to February 1919. Among them, 562 were males and 804 were females with average age (59.45±15.10) years old. The control group consisted of 70healthy donors (35 males and 35 females, with an average age of (49.60±19.12) years old), including 69 cases of venous thrombosis (thrombotic group, 32 males and37 females, with an average age of (61.20±15.71) years old).Chemoluminescent enzyme immunoassay was used to detect thromboregulatory proteins(TM), thrombin-antithrombin complexes(TAT), tissue plasminogen activators/inhibitors -1 complexes(t-PAIC), plasminase-anti-fibrinolysis complexes(PIC) in venous plasma. According to the sensitivity and specificity of each marker, the receiver′s work characteristic curve was drawn to evaluate its diagnostic performance. Cox regression analysis was used for single-factor and multi-factor risk analysis.Results:The incidence of venous thromboembolism(VTE) in patients with different types of malignant tumors was statistically significant, with lung cancer being the highest, followed by colorectal cancer and breast cancer( P<0.05). The levels of TM, TAT, t-PAIC and PIC were significantly higher in the lung, breast and colorectal thrombosis group than in the control group. The differences were statistically significant(all P<0.05). The optimal cut-off level for TM is 10.57 IU/ml(sensitivity 50.30%, specificity 75.50%, AUC=0.671), and the optimal cut-off level for TAT is 4.16 ng/ml(sensitivity is 80.30%, specificity is 62.80%, AUC=0.757).The optimal truncation level for t-PAIC is 11.44 ng/ml(sensitivity 52.50%, specificity 84.00%, AUC=0.682), and the optimal truncation level for PIC is 1.18μg/ml(sensitivity 67.20%, specificity is 79.50%, AUC=0.790). The combined detection of the four molecular markers has the best sensitivity and diagnostic performance(86.90%, AUC=0.807). Age, stage, metastasis, surgery, tumor diameter, and PIC levels are independent factors that affect the occurrence of VTE in malignant tumors (all P<0.05). Conclusions:Different types of malignant tumors have different rates of thrombosis. The combined detection ofTM, TAT, t-PAIC and PIC have the best diagnostic performance, and can be used as a new early diagnosis method for VTE in malignant tumors. Age, stage, metastasis, surgery, and tumor diameter are risk factors for VTE in malignant tumors. PIC levels can be used as a reliable markerfor the risk of VTE in patients with malignant tumors within 6 months.
ABSTRACT
Objective@#To explore the early diagnostic value of thrombus molecular markers in thrombosis ofpatients with malignant tumors and to evaluate their risk factors.@*Methods@#Diagnostic research.A total of 1366 patients (including lung cancer, breast cancer and colorectal cancer,) were randomly selected in the Red Flag Hospital of Mudanjiang Medical College and Mudanjiang Cancer Hospitalfrom September 2009 to February 1919. Among them, 562 were males and 804 were females with average age (59.45±15.10) years old. The control group consisted of 70healthy donors (35 males and 35 females, with an average age of (49.60±19.12) years old), including 69 cases of venous thrombosis (thrombotic group, 32 males and37 females, with an average age of (61.20±15.71) years old).Chemoluminescent enzyme immunoassay was used to detect thromboregulatory proteins(TM), thrombin-antithrombin complexes(TAT), tissue plasminogen activators/inhibitors -1 complexes(t-PAIC), plasminase-anti-fibrinolysis complexes(PIC) in venous plasma. According to the sensitivity and specificity of each marker, the receiver′s work characteristic curve was drawn to evaluate its diagnostic performance. Cox regression analysis was used for single-factor and multi-factor risk analysis.@*Results@#The incidence of venous thromboembolism(VTE) in patients with different types of malignant tumors was statistically significant, with lung cancer being the highest, followed by colorectal cancer and breast cancer(P<0.05). The levels of TM, TAT, t-PAIC and PIC were significantly higher in the lung, breast and colorectal thrombosis group than in the control group. The differences were statistically significant(all P<0.05). The optimal cut-off level for TM is 10.57 IU/ml(sensitivity 50.30%, specificity 75.50%, AUC=0.671), and the optimal cut-off level for TAT is 4.16 ng/ml(sensitivity is 80.30%, specificity is 62.80%, AUC=0.757).The optimal truncation level for t-PAIC is 11.44 ng/ml(sensitivity 52.50%, specificity 84.00%, AUC=0.682), and the optimal truncation level for PIC is 1.18μg/ml(sensitivity 67.20%, specificity is 79.50%, AUC=0.790). The combined detection of the four molecular markers has the best sensitivity and diagnostic performance(86.90%, AUC=0.807). Age, stage, metastasis, surgery, tumor diameter, and PIC levels are independent factors that affect the occurrence of VTE in malignant tumors (all P<0.05).@*Conclusions@#Different types of malignant tumors have different rates of thrombosis. The combined detection ofTM, TAT, t-PAIC and PIC have the best diagnostic performance, and can be used as a new early diagnosis method for VTE in malignant tumors. Age, stage, metastasis, surgery, and tumor diameter are risk factors for VTE in malignant tumors. PIC levels can be used as a reliable markerfor the risk of VTE in patients with malignant tumors within 6 months.