Xing Jiahua, Guo Lingli, Jia Ziqi, Li Yan, Han Yan
The First Medical Center, Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China.
School of Medicine, Nankai University, Tianjin 300071, China.
Cancers (Basel). 2022 Jul 22;14(15):3582. doi: 10.3390/cancers14153582.
Tumor-associated macrophages (TAMs) have gained considerable attention as therapeutic targets. Monoclonal antibody treatments directed against tumor antigens contribute significantly to cancer cell clearance by activating macrophages to phagocytose tumor cells. Due to its complicated genetic and molecular pathways, skin cutaneous melanoma (SKCM) has not yet attained the expected clinical efficacy and prognosis when compared to other skin cancers. Therefore, we chose TAMs as an entrance point. This study aimed to thoroughly assess the dysregulation and regulatory role of phagocytosis regulators in SKCM, as well as to understand their regulatory patterns in SKCM. This study subtyped prognosis-related phagocytosis regulators to investigate prognostic differences between subtypes. Then, we screened prognostic factors and constructed phagocytosis-related scoring models for survival prediction using differentially expressed genes (DEGs) between subtypes. Additionally, we investigated alternative treatment options using chemotherapeutic drug response data and clinical cohort treatment data. We first characterized and generalized phagocytosis regulators in SKCM and extensively examined the tumor immune cell infiltration. We created two phagocytosis regulator-related system (PRRS) phenotypes and derived PRRS scores using a principal component analysis (PCA) technique. We discovered that subtypes with low PRRS scores had a poor prognosis and decreased immune checkpoint-associated gene expression levels. We observed significant therapeutic and clinical improvements in patients with higher PRRS scores. Our findings imply that the PRRS scoring system can be employed as an independent and robust prognostic biomarker, serving as a critical reference point for developing novel immunotherapeutic methods.
肿瘤相关巨噬细胞（TAMs）作为治疗靶点已受到广泛关注。针对肿瘤抗原的单克隆抗体治疗通过激活巨噬细胞吞噬肿瘤细胞，对癌细胞清除有显著贡献。由于其复杂的遗传和分子途径，与其他皮肤癌相比，皮肤黑色素瘤（SKCM）尚未达到预期的临床疗效和预后。因此，我们选择TAMs作为切入点。本研究旨在全面评估SKCM中吞噬作用调节因子的失调和调节作用，以及了解它们在SKCM中的调节模式。本研究对与预后相关的吞噬作用调节因子进行亚型分类，以研究各亚型之间的预后差异。然后，我们筛选预后因素，并使用亚型之间的差异表达基因（DEG）构建用于生存预测的吞噬作用相关评分模型。此外，我们利用化疗药物反应数据和临床队列治疗数据研究替代治疗方案。我们首先对SKCM中的吞噬作用调节因子进行表征和概括，并广泛检查肿瘤免疫细胞浸润情况。我们创建了两种与吞噬作用调节因子相关的系统（PRRS）表型，并使用主成分分析（PCA）技术得出PRRS评分。我们发现PRRS评分低的亚型预后较差，免疫检查点相关基因表达水平降低。我们观察到PRRS评分较高的患者有显著的治疗和临床改善。我们的研究结果表明，PRRS评分系统可作为一种独立且可靠的预后生物标志物，为开发新型免疫治疗方法提供关键参考点。
