UNASSIGNED: To elucidate the clinical implications of VAMP7, as well as its involvement in the tumor microenvironment and molecular pathways of breast cancer.
UNASSIGNED: BC (n=100) and non-cancerous breast tissues (n= 100) were collected for an immunohistochemical experiment (1:200). The protein expression level of VAMP7 was determined by using a semi-quantitative scoring method. High-throughput RNA-sequencing data of BC tissues were analyzed to confirm the mRNA expression trend of VAMP7. Additionally, the largest BC prognosis cohort data were collected to mine the potential impact VAMP7 has on BC progression. The association between VAMP7 and the microenvironment of BC was evaluated by using a CIBERSORT algorithm. Moreover, we explored the co-expressed molecular mechanisms of VAMP7 in BC by calculating Pearson correlation coefficients and overexpressed genes. Finally, the biological mechanism underlying the relationship between VAMP7 and the key pathways was also explored using gene set enrichment analysis (GSEA). Potential therapeutic strategies were predicted targeting VAMP7.
UNASSIGNED: VAMP7 protein was significantly over-expressed in BC tissue than that in controls (p< 0.001). Compared with 459 normal breast tissues and 113 non-cancerous breast tissues, the expression level of VAMP7 mRNA was significantly increased in 1111 BC tissues. CD4+T cells, macrophages, and naïve B cells had a higher infiltration rate in BC tissues with high VAMP7 expression, while regulatory T cells and CD8+T cells had a lower infiltration rate. Over-expressed VAMP7 was associated with macrophages activation and transition from M1 to M2 polarization. Upregulated VAMP7 could predicted poorer OS, DMFS, PPS, and RFS outcomes. Upregulated VAMP7 co-expressed genes were significantly enriched in the cell cycle checkpoints. GSEA confirmed that over-expressed VAMP7 are markedly associated with functional enrichment in cell cycle related categories, including mitotic spindle, G2M checkpoint, and E2F targets. KU-55933 was predicted as a putative therapeutic drug for BC targeting VAMP7.
UNASSIGNED: VAMP7 was upregulated in BC tissue and correlated with poor prognosis of BC patients. VAMP7 may promote BC progression by targeting the cell cycle pathway.
■阐明VAMP7的临床意义,以及其在乳腺癌肿瘤微环境和分子途径中的参与。
■收集BC(n=100)和非癌乳腺组织(n=100)用于免疫组织化学实验(1:200)。通过使用半定量评分方法确定VAMP7的蛋白质表达水平。分析BC组织的高通量RNA测序数据以确认VAMP7的mRNA表达趋势。此外,我们收集了最大的BC预后队列数据,以挖掘VAMP7对BC进展的潜在影响.使用aCIBERSORT算法评估VAMP7与BC微环境之间的关联。此外,我们通过计算Pearson相关系数和过表达基因来探索VAMP7在BC中的共表达分子机制。最后,还使用基因集富集分析(GSEA)探索了VAMP7与关键途径之间关系的生物学机制。预测潜在的治疗策略靶向VAMP7。
■VAMP7蛋白在BC组织中的表达明显高于对照组(p<0.001)。与459个正常乳腺组织和113个非癌乳腺组织相比,1111BC组织中VAMP7mRNA的表达水平明显升高。CD4+T细胞,巨噬细胞,原初B细胞在高VAMP7表达的BC组织中具有较高的浸润率,而调节性T细胞和CD8+T细胞的浸润率较低。过表达的VAMP7与巨噬细胞活化和从M1到M2极化的转变有关。上调的VAMP7可以预测操作系统较差,DMFS,PPS,和RFS结果。上调的VAMP7共表达基因在细胞周期检查点中显著富集。GSEA证实过表达的VAMP7与细胞周期相关类别的功能富集显著相关。包括有丝分裂纺锤体,G2M检查点,和E2F目标。KU-55933被预测为针对BC靶向VAMP7的推定治疗药物。
■VAMP7在BC组织中上调,与BC患者的不良预后相关。VAMP7可能通过靶向细胞周期途径促进BC进展。