Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu City, 610041, Sichuan Province, People's Republic of China.
Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Clin Epigenetics. 2022 Aug 8;14(1):99. doi: 10.1186/s13148-022-01319-2.
Clear cell renal cell carcinoma (ccRCC) is the most common and highly heterogeneous subtype of renal cell carcinoma. Dysregulated basal cell adhesion molecule (BCAM) gene is associated with poor prognosis in various cancers. However, the dysregulated functions and related multi-omics features of BCAM in ccRCC stay unclear.
BCAM expression was aberrantly downregulated in ccRCC and correlated with adverse pathological parameters and poor prognosis. Low mRNA expression of BCAM was remarkably associated with its CpG methylation levels and BAP1 mutation status. Patients with lower-expressed BCAM concomitant with BAP1 mutation had a worse prognosis. Using RNA-seq data from The cancer genome atlas, we found that compared to the BCAM-high expression subgroup, ccRCC patients in the BCAM-low expression subgroup had significantly higher levels of immune infiltration, higher immune checkpoint expression levels and lower TIDE (tumor immune dysfunction and exclusion) score, indicating potential better response to immunotherapy. Data from the Clinical Proteomic Tumor Analysis Consortium further validated the association between low BCAM expression and CD8 + inflamed phenotype at protein level. Meanwhile, our results suggested that the angiogenesis-related pathways were enriched in the BCAM-high expression subgroup. More importantly, according to the data from the GDSC database, we revealed that the BCAM-high expression subgroup should be more sensitive to anti-angiogenetic therapies, including sorafenib, pazopanib and axitinib.
These results suggest that BCAM could serve as a biomarker distinguishing different tumor microenvironment phenotypes, predicting prognosis and helping therapeutic decision-making for patients with ccRCC.
透明细胞肾细胞癌（ccRCC）是最常见且高度异质性的肾细胞癌亚型。细胞基底黏附分子（BCAM）基因失调与多种癌症的不良预后相关。然而，BCAM 在 ccRCC 中的失调功能和相关多组学特征尚不清楚。
BCAM 在 ccRCC 中表达异常下调，与不良的病理参数和预后不良相关。BCAM 的低 mRNA 表达与 CpG 甲基化水平和 BAP1 突变状态显著相关。BCAM 低表达同时伴有 BAP1 突变的患者预后更差。利用癌症基因组图谱中的 RNA-seq 数据，我们发现与 BCAM 高表达亚组相比，BCAM 低表达亚组的 ccRCC 患者的免疫浸润水平显著更高，免疫检查点表达水平更高，TIDE（肿瘤免疫功能障碍和排除）评分更低，表明对免疫治疗可能有更好的反应。来自临床蛋白质组肿瘤分析联盟的进一步验证了低 BCAM 表达与 CD8+炎症表型在蛋白水平上的相关性。同时，我们的结果表明，血管生成相关途径在 BCAM 高表达亚组中富集。更重要的是，根据 GDSC 数据库的数据，我们揭示了 BCAM 高表达亚组对包括索拉非尼、帕唑帕尼和阿昔替尼在内的抗血管生成治疗应该更敏感。
这些结果表明，BCAM 可作为区分不同肿瘤微环境表型的生物标志物，预测预后，并有助于 ccRCC 患者的治疗决策。
