RESUMO
BACKGROUND: Accurate prediction of the survival of cutaneous melanoma (CM) permits the selection of the optimal treatment. Currently, the TNM stage has limitations in predicting the survival of CM. There is evidence that the WNT/ß-catenin signaling pathway has the potential to predict the CM prognosis. However, it still needs further investigation. OBJECTIVE: This study aims to establish a nomogram incorporating the WNT/ß-catenin signaling pathway to improve the predicted accuracy of the overall survival (OS) of CM. METHODS: Two hundred and eighty CM patients were recruited and followed up. The clinicopathological characteristics and the key genes of the WNT/ß-catenin signaling pathway (VEGF, ß-catenin, and DKK1) were chosen as potential variables associated with the OS. In the training cohort (n = 190), a nomogram was built to estimate the 1-, 3-, and 5-year OS, and its discriminations and calibrations were valid by the verification cohort (n = 90). The predicted accuracies of the nomogram with or without the Wnt/ß-catenin pathway and TNM stage were compared. RESULTS: A nomogram integrating independent risk factors (ulceration, lymph node metastasis, distant metastasis, Breslow thickness, dermal mitoses, ß-catenin, VEGF, and DKK1), which were evaluated by a multivariate analysis, was constructed to predict the 1-, 3-, and 5-year OS of CM patients. Good discrimination and calibration were obtained regardless of the training or validation datasets. The nomogram incorporating the Wnt/ß-catenin signaling pathway showed the highest accuracy [area under the curve (AUC)=0.914, 0.852, 0.785] compared with the nomogram without the Wnt/ß-catenin signaling pathway (AUC=0.693, 0.640, 0.615) and the TNM stage (AUC=0.726, 0.693, 0.673). CONCLUSION: The prognostic value of the established nomogram incorporating the WNT/ß-catenin signaling pathway was better than it without WNT/ß-catenin signaling pathway and TNM stage, which might be beneficial in the development of optimal treatment options.
RESUMO
This study was aimed to explore the effects of STI571 alone or with As2O3 on proliferation, apoptosis and caspase 3, bcl-xL mRNA expression of K562 cells, and the molecular mechanism of As2O3 enhancing the anti-leukemia effect of STI571 so as to provide the scientific basis for clinical treatment of chronic myeloid leukemia. The effect of drugs on proliferation of K562 cells was assayed by MTT method, the apoptosis rate of K562 cells was detected by flow cytometry with Annexin V/PI double staining, the caspase 3, bcl-xL mRNA expressions of K562 cells were determined by real time quantitative PCR. The results showed that STI571 alone or with As2O3 both could inhibit the proliferation of K562 cells. OD value in test groups reduced along with prolonging of action times, the OD values between different time points were significantly different (p < 0.05), furthermore the OD values at 72 hours in test groups were lowest, while as compared with control group, OD values at same time points in test groups all gradually decreased, among which decrease of OD value in test 5 group was most significant. The flow cytometric detection indicated that along with time prolonging, the apoptotic rate in control group not obviously changed, but the apoptotic rate in test groups gradually increased, the difference between time points was significant (p < 0.05), moreover apoptotic rate increased most obviously at 72 hours, while as compared with control group, apoptotic rate at same time points in test groups was gradually enhanced (p < 0.05), among which the apoptotic rate in test 5 group was highest. The real time qPCR assay revealed that as compared with control group, the bcl-xL mRNA expression in test groups reduced with decrease of 2-ΔΔCT value, furthermore the decrease of expression level in test 3 group was higher than that in test 2 group (p < 0.05), while the caspase 3 mRNA expression in test groups was enhanced with increase of 2-ΔΔCT value, moreover the increase of expression level in test 3 group was higher than that in test 2 group (p < 0.05). It is concluded that the STI571 can inhibit the proliferation of K562 cells, accelerate the apoptosis of K562 cells. The STI571 combined with As2O3 can enhance these two effects, increase the expression of caspase-3 mRNA and decrease the expression of bcl-xL mRNA. Therefore, the effect of STI571 combined with As2O3 on expression of caspase 3 and bcl-xL mRNA may be one of molecular mechanisms underlying their synergic antileukemia efficacy.
