Yin Zhenjie, Zhao Yu, Zhou Weiwen, You Chengcheng, Bai Yuanyuan, You Bingyong, Lu Dongming, Liao Shangfan, Zheng Luoping, Sun Yingming, Wu Yongyang
Department of Urology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, Fujian 365001, China.
Department of Medical and Radiation Oncology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, Fujian 365001, China.
J Oncol. 2023 Apr 8;2023:1302278. doi: 10.1155/2023/1302278. eCollection 2023.
The most common subtype of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC), has a high heterogeneity and aggressive nature. The basement membrane (BM) is known to play a vital role in tumor metastasis. BM-related genes remain untested in ccRCC, however, in terms of their prognostic significance.
BM-related genes were gleaned from the most recent cutting-edge research. The RNA-seq and clinical data of the ccRCC were obtained from TCGA and GEO databases, respectively. The multigene signature was constructed using the univariate Cox regression and the LASSO regression algorithm. Then, clinical features and prognostic signatures were combined to form a nomogram to predict individual survival probabilities. Using functional enrichment analysis and immune-correlation analysis, we investigated potential enrichment pathways and immunological characteristics associated with BM-related-gene signature.
In this study, we built a model of 20 BM-related genes and classified them as high-risk or low-risk, with each having its anticipated risk profile. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group in the TCGA cohort, as was confirmed by the testing dataset. Functional analysis showed that the BM-based model was linked to cell-substrate adhesion and tumor-related signaling pathways. Comparative analysis of immune cell infiltration degrees and immune checkpoints reveals a central role for BM-related genes in controlling the interplay between the immune interaction and the tumor microenvironment of ccRCC.
We combined clinical characteristics known to predict the prognosis of ccRCC patients to create a gene signature associated with BM. Our findings may also be useful for forecasting how well immunotherapies would work against ccRCC. Targeting BM may be a therapeutic alternative for ccRCC, but the underlying mechanism still needs further exploration.
肾细胞癌最常见的亚型，即透明细胞肾细胞癌（ccRCC），具有高度异质性和侵袭性。已知基底膜（BM）在肿瘤转移中起关键作用。然而，就其预后意义而言，BM相关基因在ccRCC中尚未得到检验。
从最新的前沿研究中收集BM相关基因。ccRCC的RNA测序和临床数据分别从TCGA和GEO数据库中获取。使用单变量Cox回归和LASSO回归算法构建多基因特征。然后，将临床特征和预后特征相结合，形成一个列线图，以预测个体生存概率。通过功能富集分析和免疫相关性分析，我们研究了与BM相关基因特征相关的潜在富集途径和免疫特征。
在本研究中，我们构建了一个包含20个BM相关基因的模型，并将它们分为高风险或低风险，每个都有其预期的风险概况。在TCGA队列中，高风险组患者的总生存期与低风险组患者相比显著缩短，测试数据集证实了这一点。功能分析表明，基于BM的模型与细胞-基质粘附和肿瘤相关信号通路有关。免疫细胞浸润程度和免疫检查点的比较分析揭示了BM相关基因在控制ccRCC免疫相互作用和肿瘤微环境之间相互作用中的核心作用。
我们结合已知可预测ccRCC患者预后的临床特征，创建了一个与BM相关的基因特征。我们的发现可能也有助于预测免疫疗法对ccRCC的疗效。靶向BM可能是ccRCC的一种治疗选择，但其潜在机制仍需进一步探索。
