Molecular characteristics of carcinoma arising from mature cystic teratoma of the ovary (MCT) remain unclear due to its rarity. We analyzed RNA-sequencing data of 2322 pan-cancer [1378 squamous cell carcinomas (SCC), 6 adenosquamous carcinomas (ASC), and 938 adenocarcinomas (AC)] including six carcinomas arising from MCT (four SCCs, one ASC, and one AC). Hierarchical clustering and principal component analysis showed that gene expression profiles of carcinomas arising from MCT were different between each histological type and that gene expression profiles of SCCs arising MCT (MCT-SCCs) was apparently similar to those of lung SCCs. By epidermis-associated pathways activity based on gene set enrichment analysis, 1030 SCCs were divided into two groups: epidermis-signature high (head and neck, esophagus, and skin) and low (cervix, lung, and MCT). In addition to pan-SCC transcriptome analysis, cytokeratin profiling based on immunohistochemistry in the independent samples of 21 MCT-SCCs clarified that MCT-SCC dominantly expressed CK18, suggesting the origin of MCT-SCC was columnar epithelium. Subsequently, we investigated differentially expressed genes in MCT-SCCs compared with different SCCs and identified XCL1 was specifically overexpressed in MCT-SCCs. Through immunohistochemistry analysis, we identified XCL1 expression on tumor cells in 13/24 (54%) of MCT-SCCs but not in MCTs. XCL1 expression was also significantly associated with the number of tumor-infiltrating CD8-positive T cells and PD-L1 expression on tumor cells. XCL1 produced by tumor cells may induce PD1/PD-L1 interaction and dysfunction of CD8-positive T cells in tumor microenvironment. XCL1 expression may be a novel biomarker for malignant transformation of MCT into SCC and a biomarker candidate for therapeutic response to an anti-PD1/PD-L1 therapy.

卵巢成熟囊性畸胎瘤 (MCT) 引起的癌的分子特征由于其罕见性而仍不清楚。我们分析了 2322 例泛癌 [1378 例鳞状细胞癌 (SCC)、6 例腺鳞癌 (ASC) 和 938 例腺癌 (AC)] 的 RNA 测序数据，包括由 MCT 引起的 6 例癌（4 例 SCC、1 例 ASC 和 1 例 AC） ）。分层聚类和主成分分析表明，MCT 引起的癌的基因表达谱在每种组织学类型之间是不同的，并且 MCT 引起的 SCC (MCT-SCCs) 的基因表达谱与肺 SCC 的基因表达谱明显相似。通过基于基因集富集分析的表皮相关通路活性，将 1030 个 SCC 分为两组：表皮特征高（头颈部、食道和皮肤）和低（宫颈、肺和 MCT）。除了泛 SCC 转录组分析外，基于免疫组织化学对 21 个 MCT-SCC 的独立样本进行的细胞角蛋白分析阐明了 MCT-SCC 主要表达 CK18，这表明 MCT-SCC 的起源是柱状上皮。随后，我们研究了 MCT-SCC 中与不同 SCC 相比的差异表达基因，并确定了XCL1在 MCT-SCC 中特异性过表达。通过免疫组织化学分析，我们在 13/24 (54%) 的 MCT-SCC 中发现了 XCL1 在肿瘤细胞上的表达，但在 MCT 中没有。XCL1 表达也与肿瘤浸润性 CD8 阳性 T 细胞的数量和肿瘤细胞上的 PD-L1 表达显着相关。肿瘤细胞产生的 XCL1 可诱导肿瘤微环境中 CD8 阳性 T 细胞的 PD1/PD-L1 相互作用和功能障碍。XCL1 表达可能是 MCT 向 SCC 恶性转化的新生物标志物，也是抗 PD1/PD-L1 治疗反应的候选生物标志物。