透明细胞肾细胞癌（ccRCC）是肾癌的一种常见亚型，具有复杂的肿瘤微环境，显着影响肿瘤进展和免疫治疗反应。近年来，新出现的证据强调了肿瘤浸润 B 淋巴细胞 (TIL-B)（适应性免疫的重要组成部分）的参与，以及与其他肿瘤相比，它们在 ccRCC 中的作用。因此，本研究致力于系统地探讨 ccRCC 中 TIL-B 的预后和分子特征。最初，xCell 算法用于预测 TCGA-KIRC 和其他 ccRCC 转录组数据集中的 TIL-B。应用 Log-Rank 检验和 Cox 回归来探索 B 细胞与 ccRCC 存活的关系。然后，我们使用WGCNA方法结合共识子簇和scRNA-seq数据分析来识别与TIL-Bs相关的重要模块。为了缩小潜在生物标志物的范围，提出了预后特征。接下来，我们探讨了特征个体基因和风险评分的特征。最后，研究了特征与临床表型和药物的潜在关联。初步，我们发现 ccRCC 存活率与 TIL-B 呈负相关，这也得到了其他数据集的证实。随后，鉴定出了十个共表达模块，并随后检测到了一个独特的 ccRCC 簇。此外，我们评估了 ccRCC 中 B 细胞的转录组改变，并确定了相关的 B 细胞亚型。基于两个核心模块（棕色、红色），在训练集中开发了 10 个基因签名（TNFSF13B、SHARPIN、B3GAT3、IL2RG、TBC1D10C、STAC3、MICB、LAG3、SMIM29、CTLA4）并在测试集中进行了验证。进一步研究了这些生物标志物的差异表达和与免疫特征的相关性，以及风险评分相关的突变和途径。最后，我们建立了组合肿瘤分级的列线图，并根据其敏感性反应发现了潜在药物。在我们的研究中，我们阐明了 ccRCC 和 B 细胞之间的显着关联。然后，我们检测到了几个关键基因模块，以及密切的患者亚群和 B 细胞亚型，它们可能与 ccRCC 中的 TIL-B 相关。此外，我们提出了10个基因特征，并从多个角度研究了其分子特征。总体而言，了解 TIL-B 的作用可能有助于 ccRCC 的免疫治疗方法，值得进一步研究以阐明对患者预后和治疗的影响。版权所有 © 2023 Yue、Cai、Lu、Sechi、Solla 和 Li。

Clear cell renal cell carcinoma (ccRCC) is a prevalent subtype of kidney cancer that exhibits a complex tumor microenvironment, which significantly influences tumor progression and immunotherapy response. In recent years, emerging evidence has underscored the involvement of tumor-infiltrating B lymphocytes (TIL-Bs), a crucial component of adaptive immunity, and their roles in ccRCC as compared to other tumors. Therefore, the present study endeavors to systematically explore the prognostic and molecular features of TIL-Bs in ccRCC.Initially, xCell algorithm was used to predict TIL-Bs in TCGA-KIRC and other ccRCC transcriptomic datasets. The Log-Rank test and Cox regression were applied to explore the relationship of B-cells with ccRCC survival. Then, we used WGCNA method to identify important modules related to TIL-Bs combining Consensus subcluster and scRNA-seq data analysis. To narrow down the prospective biomarkers, a prognostic signature was proposed. Next, we explored the feature of the signature individual genes and the risk-score. Finally, the potential associations of signature with clinical phenotypes and drugs were investigated.Preliminary, we found ccRCC survival was negatively associated with TIL-Bs, which was confirmed by other datasets. Afterwards, ten co-expression modules were identified and a distinct ccRCC cluster was subsequently detected. Moreover, we assessed the transcriptomic alteration of B-cell in ccRCC and a relevant B-cell subtype was also pinpointed. Based on two core modules (brown, red), a 10-gene signature (TNFSF13B, SHARPIN, B3GAT3, IL2RG, TBC1D10C, STAC3, MICB, LAG3, SMIM29, CTLA4) was developed in train set and validated in test sets. These biomarkers were further investigated with regards to their differential expression and correlation with immune characteristics, along with risk-score related mutations and pathways. Lastly, we established a nomogram combined tumor grade and discovered underlying drugs according to their sensitivity response.In our research, we elucidated the remarkable association between ccRCC and B-cells. Then, we detected several key gene modules, together with close patient subcluster and B-cell subtype,which could be responsible for the TIL-Bs in ccRCC. Moreover, we proposed a 10-gene signature and investigated its molecular features from multiple perspectives. Overall, understanding the roles of TIL-Bs could aid in the immunotherapeutic approaches for ccRCC, which deserve further research to clarify the implications for patient prognosis and treatment.Copyright © 2023 Yue, Cai, Lu, Sechi, Solla and Li.