背景:2018年全球肾细胞癌(RCC)导致403,262例新病例,占全球癌症的2.2%,然而,舒尼替尼,RCC的主要靶向治疗剂之一,通常由于抵抗而无效。新出现的证据表明舒尼替尼可以影响肿瘤环境,这已被证明是肿瘤进展的重要因素。
方法:在本研究中,我们使用ssGSEA从GSE65615,TCGA中提取透明细胞RCC(ccRCC)和正常对照样品的免疫浸润丰度,和GTEx;关键免疫细胞通过学生t检验和单变量Cox分析确定。然后应用共表达网络结合差异表达分析得出ccRCC的关键免疫相关基因,然后使用差异表达分析鉴定hub基因。随后,在KEGG中进行了生物学功能以及免疫相关和舒尼替尼相关特征的探索和验证,TISIB,Oncomine,ICGC,和GEO数据库。
结果:我们对未成熟树突状细胞和中枢记忆性CD4T细胞进行了精制,这些细胞与舒尼替尼和ccRCC相关。Follows,五个hub基因(CRYBB1、RIMBP3C、CEACAM4,HAMP,和LYL1)与舒尼替尼和ccRCC中的免疫浸润密切相关。在外部数据中进一步验证完善的CRYBB1,CEACAM4和HAMP在舒尼替尼耐药中起着至关重要的作用,ccRCC中的免疫浸润,以及ccRCC的发展和进展。总之,我们的研究结果可以揭示ccRCC中舒尼替尼的耐药性,并为ccRCC提供新的生物标志物或药物靶标.
BACKGROUND: Renal cell carcinoma (RCC) contributed to 403,262 new cases worldwide in 2018, which constitutes 2.2% of global cancer, nevertheless, sunitinib, one of the major targeted therapeutic agent for RCC, often developed invalid due to resistance. Emerging evidences suggested sunitinib can impact tumor environment which has been proven to be a vital factor for tumor progression.
METHODS: In the present study, we used ssGSEA to extract the immune infiltrating abundance of clear cell RCC (ccRCC) and normal control samples from GSE65615, TCGA, and GTEx; key immune cells were determined by Student\'s t-test and univariable Cox analysis. Co-expression network combined with differentially expressed analysis was then applied to derive key immune-related genes for ccRCC, followed by the identification of hub genes using differential expression analysis. Subsequently, explorations and validations of the biological function and the immune-related and sunitinib-related characteristics were conducted in KEGG, TISIDB, Oncomine, ICGC, and GEO databases.
RESULTS: We refined immature dendritic cells and central memory CD4 T cells which showed associations with sunitinib and ccRCC. Following, five hub genes (
CRYBB1, RIMBP3C, CEACAM4, HAMP, and LYL1) were identified for their strong relationships with sunitinib and immune infiltration in ccRCC. Further validations in external data refined
CRYBB1, CEACAM4, and HAMP which play a vital role in sunitinib resistance, immune infiltrations in ccRCC, and the development and progression of ccRCC. In conclusion, our findings could shed light on the resistance of sunitinib in ccRCC and provide novel biomarkers or drug targets for ccRCC.