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鉴定无活性的 a motif 结构域包含 9 样蛋白作为皮肤黑色素瘤患者的潜在生物标志物。

Identification of sterile a-motif domain-containing 9-like as a potential biomarker in patients with cutaneous melanoma.

机构信息

The Department of Scientific Education, The First People's Hospital of Jiande, Hangzhou, China.

Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China.

出版信息

PeerJ. 2023 Jul 5;11:e15634. doi: 10.7717/peerj.15634. eCollection 2023.

Abstract

Skin cutaneous melanoma (SKCM) is one of the most aggressive malignancies, accounting for approximately 75% of skin cancer-related fatalities annually. Sterile a-motif domain-containing 9-like (SAMD9L) has been found to regulate cell proliferation and suppress the neoplastic phenotype, but its specific role in SKCM remains unknown. To investigate the cancer-associated immunology of SKCM and the role of SAMD9L in tumor progression, we conducted an integrative bioinformatics analysis that revealed elevated expression levels of SAMD9L in SKCM. ROC curves and survival analyses confirmed the considerable diagnostic and prognostic abilities of SAMD9L. Moreover, a real-world cohort of 35 SKCM patients from the First Affiliated Hospital of Soochow University showed that higher expression levels of SAMD9L were associated with better prognosis. We performed validation experiments, including cell culture, generation of lentiviral-transfected SKCM cell lines, cell proliferation assay, and transwell assay, which demonstrated that down-regulation of SAMD9L significantly promoted proliferation and migration capacities of SKCM cells. Additionally, SAMD9L expression was found to be strongly linked to immune infiltration. Our results revealed a positive correlation between SAMD9L and XAF1 expression, suggesting that SAMD9L may serve as a prospective prognostic indicator of SKCM with co-expressed XAF1 gene. In summary, our findings indicate that SAMD9L may serve as a promising prognostic and therapeutic biomarker and play a critical role in tumor-immune interactions in SKCM.

摘要

皮肤皮肤黑色素瘤(SKCM)是最具侵袭性的恶性肿瘤之一,每年约占与皮肤癌相关死亡人数的 75%。无菌 a- motif 结构域包含 9 样(SAMD9L)已被发现可调节细胞增殖并抑制肿瘤表型,但它在 SKCM 中的具体作用尚不清楚。为了研究 SKCM 的癌症相关免疫学和 SAMD9L 在肿瘤进展中的作用,我们进行了综合生物信息学分析,结果显示 SAMD9L 在 SKCM 中的表达水平升高。ROC 曲线和生存分析证实了 SAMD9L 具有相当的诊断和预后能力。此外,来自苏州大学第一附属医院的 35 名 SKCM 患者的真实世界队列表明,SAMD9L 的高表达水平与更好的预后相关。我们进行了验证实验,包括细胞培养、生成慢病毒转染的 SKCM 细胞系、细胞增殖测定和 Transwell 测定,结果表明 SAMD9L 的下调显著促进了 SKCM 细胞的增殖和迁移能力。此外,SAMD9L 的表达与免疫浸润密切相关。我们的结果显示 SAMD9L 与 XAF1 表达之间存在正相关,表明 SAMD9L 可能作为 SKCM 的一个有前途的预后指标,与共同表达的 XAF1 基因相关。总之,我们的研究结果表明 SAMD9L 可能作为 SKCM 的一个有前途的预后和治疗生物标志物,并在 SKCM 的肿瘤免疫相互作用中发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a579/10329423/d8a7012ffafb/peerj-11-15634-g001.jpg

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