ABSTRACT
ABSTRACT Background: The depth of response to platinum in urothelial neoplasm tissues varies greatly. Biomarkers that have practical value in prognosis stratification are increasingly needed. Our study aimed to select a set of BC (bladder cancer)-related genes involved in both platinum resistance and survival, then use these genes to establish the prognostic model. Materials and Methods: Platinum resistance-related DEGs (differentially expressed genes) and tumorigenesis-related DEGs were identified. Ten most predictive co-DEGs were acquired followed by building a risk score model. Survival analysis and ROC (receiver operating characteristic) plot were used to evaluate the predictive accuracy. Combined with age and tumor stages, a nomogram was generated to create a graphical representation of survival rates at 1-, 3-, 5-, and 8-year in BC patients. The prognostic performance was validated in three independent BC datasets with platinum-based chemotherapy. The potential mechanism was explored by enrichment analysis. Results: PPP2R2B, TSPAN7, ATAD3C, SYT15, SAPCD1, AKR1B1, TCHH, AKAP12, AGLN3, and IGF2 were selected for our prognostic model. Patients in high- and low-risk groups exhibited a significant survival difference with HR (hazard ratio) = 2.7 (p < 0.0001). The prognostic nomogram of predicting 3-year OS (overall survival) for BC patients could yield an AUC (area under the curve) of 0.819. In the external validation dataset, the risk score also has a robust predictive ability. Conclusion: A prognostic model derived from platinum resistance-related genes was constructed, we confirmed its value in predicting platinum-based chemotherapy benefits and overall survival for BC patients. The model might assist in therapeutic decisions for bladder malignancy.
ABSTRACT
To observe the anti-tumor effect of adoptive immunotherapy with CTL induced by PSA-pulsed dendritic cell vaccine against prostate cancer in mice. Methods: Nude mice were s. c. inoculated with LNCaP tumor cells to establish prostate cancer model. CTL induced in vitro by different peptide-pulsed dendritic cells (Non-DC,Ova-DC,Lys-DC and PSA-DC) were used for adoptive immunotherapy of experiment nude model through vena caudalis on d 15 and d 22 after inoculation. The survival of nude mice and the sizes of tumors were observed with d 50 after the initial treatment as the endpoint. Results: The tumor sizes in Non-DC, Ova-DC, Lys-DC and PSA-DC groups on d 30 and d 50 after adoptive immunotherapy were significantly larger than that at d 15 after inoculation (P<0. 01). The tumors sizes in Lys-DC and PSA-DC groups were significantly smaller than those in the Non-DC and Ova-DC groups(P<0. 01). The survival periods of animals in Lys-DC and PSA-DC groups were significantly longer than those in the Non-DC and Ova-DC groups (P<0. 01). Conclusion: Adoptive immunotherapy with CTL induced by DC-based PSA vaccine can inhibit the growth of prostate cancer LNCaP cells in nude mice and increase the survival of the animals.