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PLOD2 作为口腔鳞状细胞癌不良预后生物标志物的识别与验证

英文原题：Identification and Validation of PLOD2 as an Adverse Prognostic Biomarker for Oral Squamous Cell Carcinoma.

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Identification and Validation of PLOD2 as an Adverse Prognostic Biomarker for Oral Squamous Cell Carcinoma.

PubMed 2021/12/07（内容时间） Biomolecules Q1 · IF 5.6（JCR 2025）

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头颈部鳞癌地区：中国
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研究概要

PLOD2 是 OSCC 患者 OS 的不良预后生物标志物，可能通过 EMT 通路影响 OSCC 的转移。这些发现可能为未来 PLOD2 靶向 OSCC 治疗的研究提供新的视角。

研究思路结论见上方概要

背景

脯氨酰羟化酶2（PLOD2）是催化赖氨酸羟基化的关键酶，在多种实体瘤的进展中发挥重要作用。然而，其在口腔鳞状细胞癌（OSCC）中的空间表达谱和预后意义尚未被揭示。材料：采用质谱法探索28例患者OSCC肿瘤组织与配对正常组织之间的氨基酸扰动。随后，利用多个公共数据库和18对OSCC患者组织评估PLOD2 mRNA和蛋白水平。此外，通过免疫组化在100例OSCC患者中研究PLOD2空间表达谱，并评估其诊断和预后价值。最后，使用基因集富集分析（GSEA）研究PLOD2在OSCC中的潜在功能。

结果

赖氨酸在OSCC组织中显著升高，可有效区分肿瘤与正常组织（AUC = 0.859，p = 0.0035）。与nontumor组织相比，PLOD2 mRNA和蛋白水平在头颈部鳞状细胞癌（HNSCC）肿瘤组织（p < 0.001）和OSCC肿瘤组织中高度升高（p < 0.001）。在组织病理学上，PLOD2在OSCC患者的肿瘤细胞（TCs）和成纤维细胞样细胞（FLCs）中普遍表达，但在TIL（肿瘤浸润淋巴细胞）（TILs）中缺失。TCs中PLOD2高表达（PLOD2 TCs）和FLCs中PLOD2高表达（PLOD2 FLCs）的患者表现出低分化、更差的侵袭模式（WPOI）和更多的淋巴结转移（LNM），导致更高的术后转移风险和较差的生存时间。然而，PLOD2 FLCs而非PLOD2 TCs是OSCC患者生存结局的独立危险因素。在分子水平上，GSEA显示高表达的PLOD2主要富集于上皮-间充质转化（EMT）、TGF-beta信号通路和缺氧通路，这些通路与OSCC患者的不良临床结局相关。

展开英文摘要原文
BACKGROUND

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been revealed. MATERIALS: Mass spectrometry was used to explore amino acid perturbations between OSCC tumor tissues and paired normal tissues of 28 patients. Then, PLOD2 mRNA and protein levels were assessed using several public databases and 18 pairs of OSCC patients' tissues. Additionally, PLOD2 spatial expression profiles were investigated in 100 OSCC patients by immunohistochemistry and its diagnostic and prognostic values were also evaluated. Lastly, gene set enrichment analysis (GSEA) was used to investigate the potential functions of PLOD2 in OSCC.

RESULTS

Lysine was significantly elevated in OSCC tissues and could effectively distinguish tumor from normal tissues (AUC = 0.859, p = 0.0035). PLOD2 mRNA and protein levels were highly increased in tumor tissues of head and neck squamous cell carcinoma (HNSCC) ( p < 0.001) and OSCC compared with those in nontumor tissues ( p < 0.001). Histopathologically, PLOD2 was ubiquitously expressed in tumor cells (TCs) and fibroblast-like cells (FLCs) of OSCC patients but absent in tumor-infiltrating lymphocytes (TILs). Patients with highly expressed PLOD2 in TCs (PLOD2 TCs ) and FLCs (PLOD2 FLCs ) showed poor differentiation, a worse pattern of invasion (WPOI) and more lymph node metastasis (LNM), contributing to higher postoperative metastasis risk and poor survival time. However, PLOD2 FLCs rather than PLOD2 TCs was an independent risk factor for survival outcomes in OSCC patients. Molecularly, GSEA demonstrated highly expressed PLOD2 was mainly enriched in epithelial-mesenchymal transformation (EMT), TGF-beta signaling and hypoxia pathway, which are associated with poor clinical outcomes of OSCC patients.

CONCLUSIONS

PLOD2 was a poor prognostic biomarker for OSCC patients and may affect the metastasis of OSCC through EMT pathway. These findings might shed novel sights for future research in PLOD2 targeted OSCC therapy.

论文信息

作者
Sun Y、Wang S、Zhang X、Wu Z、Li Z、Ding Z、Huang X、Chen S
单位
Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China.China
文献类型
非美国政府资助研究
期刊
Biomolecules2021 Dec 7
原文标识
PubMed 34944486　·　DOI 10.3390/biom11121842

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