为探索放射治疗抵抗机制并寻找前列腺癌的预后生物标志物，我们从GEO和UCSC Xena数据库中选择并下载了GSE192817和TCGA PRAD数据集。对来自GSE192817的52个肿瘤细胞样本进行了差异表达和功能注释分析。然后，应用ssGSEA或GSVA算法对GSE192817和TCGA PRAD数据集中的样本进行了生物功能活性的定量评分，结合从分子特征数据库（MSigDB）中收集的特定基因集。随后，采用Wilcoxon秩和检验比较了细胞类型或PRAD患者之间的ssGSEA或GSVA评分差异。此外，对DU145和PC3细胞（前列腺癌细胞）进行了放射治疗抵抗相关基因的筛选，并使用生存分析评估这些基因预测PRAD患者预后的效果。 在GSE192817的癌细胞中检测到114个在两个或更多种不同癌细胞类型中差异表达，并与假手术或放射治疗（X射线或光子照射）相关的基因。对前列腺癌细胞（DU145和PC3）中假手术和放射治疗之间的DNA损伤相关ssGSEA评分进行比较发现，光子照射可能比X射线治疗更有效。在TCGA PRAD数据集中，接受放射治疗的患者具有更高的"GOBP_CELLULAR_RESPONSE_TO_DNA_DAMAGE_STIMULUS"，"GOBP_G2_DNA_DAMAGE_CHECKPOINT"和"GOBP_INTRA_S_DNA_DAMAGE_CHECKPOINT" GSVA评分，其Wilcoxon秩和检验p值分别为0.0005，0.0062和0.0800。此外，在放射治疗后，DU145细胞（相比于PC3细胞对X射线照射具有抵抗性）中SRXN1的表达上调，并且患者中低表达SRXN1利于放射治疗结果。PFS的对数秩和检验p值为0.0072。 放射治疗可以损伤DNA并诱导氧化应激以杀死肿瘤细胞。在本研究中，我们发现抗氧化应激基因SRXN1在前列腺癌放射治疗中扮演重要角色，并且该基因也是预测接受放射治疗患者预后的潜在生物标志物。© 2023. BioMed Central Ltd., part of Springer Nature.

To explore the mechanisms of radiotherapy resistance and search for prognostic biomarkers for prostate cancer.The GSE192817 and TCGA PRAD datasets were selected and downloaded from the GEO and UCSC Xena databases. Differential expression and functional annotation analyses were applied to 52 tumour cell samples from GSE192817. Then, the ssGSEA or GSVA algorithms were applied to quantitatively score the biological functional activity of samples in the GSE192817 and TCGA PRAD datasets, combined with specific gene sets collected from the Molecular Signatures Database (MSigDB). Subsequently, the Wilcoxon rank-sum test was used to compare the differences in ssGSEA or GSVA scores among cell types or PRAD patients. Moreover, radiotherapy resistance-associated gene screening was performed on DU145 and PC3 cells (prostate cancer cells), and survival analysis was used to evaluate the efficacy of these genes for predicting the prognosis of PRAD patients.A total of 114 genes that were differentially expressed in more than two different cancer cell types and associated with either sham surgery or radiotherapy treatment (X-ray or photon irradiation) were detected in cancer cells from GSE192817. Comparison of DNA damage-related ssGSEA scores between sham surgery and radiotherapy treatment in prostate cancer cells (DU145 and PC3) showed that photon irradiation was potentially more effective than X-ray treatment. In the TCGA PRAD dataset, patients treated with radiotherapy had much higher "GOBP_CELLULAR_RESPONSE_TO_DNA_DAMAGE_STIMULUS", "GOBP_G2_DNA_DAMAGE_CHECKPOINT" and "GOBP_INTRA_S_DNA_DAMAGE_CHECKPOINT" GSVA scores, and the Wilcoxon rank-sum test p values were 0.0005, 0.0062 and 0.0800, respectively. Furthermore, SRXN1 was upregulated in DU145 cells (resistant to X-ray irradiation compared to PC3 cells) after radiotherapy treatment, and low SRXN1 expression in patients was beneficial to radiotherapy outcomes. The log-rank test p value for PFS was 0.0072.Radiotherapy can damage DNA and induce oxidative stress to kill tumour cells. In this study, we found that SRXN1, as an antioxidative stress gene, plays an important role in radiotherapy for prostate cancer treatment, and this gene is also a potential biomarker for predicting the prognosis of patients treated with radiotherapy.© 2023. BioMed Central Ltd., part of Springer Nature.