Department of Dermatovenereology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
BMC Cancer. 2023 Mar 31;23(1):292. doi: 10.1186/s12885-023-10625-8.
Skin cutaneous melanoma (SKCM) is an extremely malignant tumor and accounts for the majority of skin cancer deaths. Aspartate beta-hydroxylase domain containing 1 (ASPHD1) may participate in cancer progression through controlling α-ketoglutarate-dependent dioxygenases. However, its role in skin cutaneous melanoma (SKCM) has not been well studied.
The gene expression data of ASPDH1 and differentially expressed genes (DEGs) from TCGA and GTEx were evaluated, and verified via the GEO database. Then, we performed GO/KEGG, GSEA, PPI network analysis to analyze the functional implications of the DEGs related to ASPHD1. Then, the association between the ASPHD1 expression and clinical parameters was investigated by Cox regression analysis. Subsequently, the survival time of SKCM patients was evaluated by plotting Kaplan-Meier curves. Moreover, we investigated the correlation between the ASPHD1 expression and lymphocytic infiltration by using the data from TISIDB and TIMER 2.0. Next, we explored the association between ASPHD1 expression and drug sensitivity. Finally, we validate the expression differences by analyzing the results of qPCR, Western blot from human normal epidermal melanocytes and melanoma cells, and immunohistochemistry (IHC) from non-tumor skin as well as melanoma tissues.
The ASPHD1 expression level was significantly upregulated in several cancers, including SKCM especially SKCM-metastasis tissues, and patients with an increased ASPHD1 expression had longer overall survival time than low expression ones. The functional enrichment analysis of ASPHD1-related DEGs showed an association with cell development regulation and tumorigenic pathways. Furthermore, the increased ASPHD1 expression level was associated with the level of immunostimulors, immunoinhibitors, chemokines, and TILs, such as CD4, CD8 T cell, mast cell, Th2 cell, and dendritic cell. More interesting, we found that ASPHD1 expression was tightly associated with CTLA4 and CD276 which are immune checkpoint markers. Moreover, the upregulated expression of ASPHD1 exhibited higher IC50 values for 24 chemotherapy drugs, including doxorubicin, and masitinib. Finally, the differential expression of ASPHD1 in SKCM was validated by the results of qPCR, Western blot, and IHC.
The expression of ASPHD1 in SKCM patients is closely related to patient survival. ASPHD1 may participate in the regulation of tumor immune microenvironment. Additionally, it may serve as a prognostic biomarker for SKCM and future in-depth studies are necessary to explore its value.
皮肤黑色素瘤（SKCM）是一种极其恶性的肿瘤，占皮肤癌死亡人数的大部分。天门冬氨酸β-羟化酶结构域包含 1（ASPHD1）可通过控制α-酮戊二酸依赖性加双氧酶参与癌症的进展。然而，它在皮肤黑色素瘤（SKCM）中的作用尚未得到很好的研究。
评估来自 TCGA 和 GTEx 的 ASBHAD1 的基因表达数据和差异表达基因（DEGs），并通过 GEO 数据库进行验证。然后，我们进行 GO/KEGG、GSEA、PPI 网络分析，以分析与 ASBHAD1 相关的 DEGs 的功能含义。然后，通过 Cox 回归分析研究 ASBHAD1 表达与临床参数之间的关联。随后，通过绘制 Kaplan-Meier 曲线评估 SKCM 患者的生存时间。此外，我们通过使用 TISIDB 和 TIMER 2.0 中的数据研究了 ASBHAD1 表达与淋巴细胞浸润之间的相关性。接下来，我们通过分析来自人正常表皮黑素细胞和黑素瘤细胞的 qPCR、Western blot 以及非肿瘤皮肤和黑素瘤组织的免疫组织化学（IHC）结果，探讨了 ASBHAD1 表达与药物敏感性的关系。最后，我们通过分析 qPCR、Western blot 和 IHC 的结果验证了表达差异，来自人正常表皮黑素细胞和黑素瘤细胞以及非肿瘤皮肤和黑素瘤组织。
ASBHAD1 的表达水平在几种癌症中显著上调，包括 SKCM，尤其是 SKCM-转移组织，并且表达增加的 ASBHAD1 的患者的总生存时间长于表达低的患者。ASBHAD1 相关 DEGs 的功能富集分析表明与细胞发育调节和致瘤途径有关。此外，ASBHAD1 表达水平的升高与免疫刺激物、免疫抑制剂、趋化因子和 TILs（如 CD4、CD8 T 细胞、肥大细胞、Th2 细胞和树突状细胞）的水平相关。更有趣的是，我们发现 ASBHAD1 表达与免疫检查点标记物 CTLA4 和 CD276 密切相关。此外，ASBHAD1 的上调表达对包括多柔比星和马替尼在内的 24 种化疗药物的 IC50 值更高。最后，通过 qPCR、Western blot 和 IHC 的结果验证了 SKCM 中 ASBHAD1 的差异表达。
SKCM 患者 ASBHAD1 的表达与患者的生存密切相关。ASBHAD1 可能参与肿瘤免疫微环境的调节。此外，它可能是 SKCM 的预后生物标志物，需要进一步深入研究以探讨其价值。
