Glucose metabolism and systemic inflammation have been associated with cancer aggressiveness and patient prognosis in various malignancies. This study aimed to evaluate the prognostic significance of pretreatment GLR(glucose to lymphocyte ratio) and systemic immune inflammation in patients with pancreatic cancer. We studied 360 patients with pathologically diagnosed pancreatic adenocarcinoma that was clinically unresectable. Baseline clinicopathological characteristics and laboratory investigations including fasting blood glucose, platelet count, lymphocyte count, neutrophil count, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), and follow-up data were collected for further analysis. The patients were randomly divided into a training cohort (n = 238) and a validation cohort (n = 122). Univariate and multivariate Cox proportional hazard regression analyses were performed to identify the prognostic value of GLR, systemic immune-inflammation markers, and tumor biomarkers. A nomogram model was developed based on the identified prognostic factors, and we used the C-index to evaluate the accuracy of the Cox regression model prediction. Multivariate analysis revealed that GLR [hazard ratio (HR): 2.597; 95% confidence interval (CI): 1.728-3.904)] and CA199 (HR: 2.484; 95% CI: 1.295-4.765) are independent predictors of poor overall survival in the training cohort and were incorporated into the nomogram for OS as independent factors. Moreover, the C-index analyses demonstrated that the C-indexes in the training cohort and the validation cohort were 0.674 and 0.671, respectively. The nomogram model predicts overall survival relatively accurately. We found that the baseline GLR is an independent prognostic factor for patients with pancreatic cancer, and the proposed nomogram can be used as an effective tool for predicting the outcomes of prognosis of patients with pancreatic cancer.
Chemotherapy is widely used for the treatment of ovarian cancer. Since chemotherapy resistance is the major cause of poor prognosis in patients with ovarian cancer, it is important to identify new methods to improve the efficacy of chemotherapy. Minichromosome maintenance complex component 2 (MCM2), which serves an essential role in DNA replication, has been recently identified as a novel proliferation marker with prognostic implications in multiple types of cancer. However, the role of MCM2 in ovarian cancer and its underlying molecular mechanisms remain unclear. Therefore, in the present study, the biological effects of MCM2 were investigated, particularly with respect to DNA damage and repair. In the present study, short hairpin RNA was employed to knockdown MCM2 expression in the A2780 ovarian cancer cell line. The sensitivity of A2780 cells to carboplatin was assessed by cell colony formation assay. The present results suggested that MCM2 knockdown inhibited the proliferation of tumor cells, induced G0/G1 phase arrest and did not exhibit effects on cell apoptosis. However, MCM2 knockdown significantly decreased the colony formation of A2780 cells treated with carboplatin. Furthermore, knockdown of MCM2 together with carboplatin treatment or UV irradiation increased the protein expression level of γ-H2A histone family member X and p53 compared with control cells. The present data suggested that the increased sensitivity to carboplatin may occur via the p53-dependent apoptotic response. Additionally, the present results suggested that knockdown of MCM2 may have therapeutic applications in enhancing the efficacy of carboplatin in patients with ovarian cancer.
To identify serum microRNA-25 (miR-25) as a diagnostic biomarker for pancreatic cancer (PCa) and to evaluate its supplementary role with serum carbohydrate antigen 19-9 (CA19-9) in early identification of cancers. Eighty patients with pancreatic cancer and 91 non-cancer controls were enrolled in this study. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of miR-25. Levels of CA19-9, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) were measured by chemiluminescent immunoassay. The logistic model was established to evaluate the correlation of miR-25 with clinical characteristics. A risk model for PCa was conducted by R statistical software. Diagnostic utility for PCa and correlation with clinical characteristics were analyzed. The expression level of miR-25, in the PCa group was significantly higher ( P < .05). Risk Model illustrated the relation between miR-25 and pancreatic cancer. With the combination of CA19-9, the performance of miR-25 in early stages (I+II) in the diagnosis of PCa was profoundly better than CA19-9 and miR-25 alone. This combination was more effective for discriminating PCa from non-cancer controls (AUC-ROC, 0.985; sensitivity, 97.50%; specificity, 90.11%) compared with CA19-9 alone or the combination of CA19-9 and CA125. The expression level of miR-25 among pancreatic cancer patients was significantly higher than that in the control group. miR-25 existed as one of the most relevant factors of PCa. miR-25 can serve as a novel noninvasive approach for PCa diagnosis, and with the supplementary of CA19-9, the combination was more effective, especially in early tumor screening.
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