Department of Oral Pathology, Institute of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Nagasaki University Dental School, Nagasaki, Japan.
Oral Dis. 2023 Nov;29(8):3193-3204. doi: 10.1111/odi.14277. Epub 2022 Jun 29.
We previously reported that dickkopf WNT signaling inhibitor 3 (DKK3) would modulate malignant potential of oral squamous cell carcinoma (OSCC) via activating Akt. Recently, cytoskeleton associated protein 4 (CKAP4) functions as receptor of DKK3, which activates Akt in esophageal squamous cell carcinoma, but its expression and function in OSCC were unclear.
We studied DKK3 and CKAP4 protein expression in OSCC tissue and investigated the correlation between protein expression and clinical data. We also investigated whether antibodies (Ab) for DKK3 or CKAP4 could suppress malignant potential of the cancer cells.
DKK3/CKAP4 protein expression was observed in majority of OSCC cases and was associated with significantly higher T-stage and TNM stage. Multivariate analysis revealed that DKK3 and CKAP4 were independent prognostic biomarkers for overall survival (OS) and disease-free survival (DFS), respectively. Survival analyses revealed that DKK3-positive cases and CKAP4-positive cases showed significantly shorter OS and DFS, respectively, and that DKK3/CKAP4 double-negative cases showed significantly favorable prognosis. Both anti-DKK3Ab and anti-CKAP4Ab could suppress cancer cell proliferation, migration, and invasion.
DKK3/CKAP4 axis is thought to be important in OSCC, and it would be a promising therapeutic target.
我们之前报道过 WNT 信号通路抑制剂 dickkopf（DKK）3 通过激活 Akt 来调节口腔鳞状细胞癌（OSCC）的恶性潜能。最近，细胞骨架相关蛋白 4（CKAP4）作为 DKK3 的受体，在食管鳞状细胞癌中激活 Akt，但它在 OSCC 中的表达和功能尚不清楚。
我们研究了 OSCC 组织中 DKK3 和 CKAP4 蛋白的表达，并探讨了蛋白表达与临床数据之间的相关性。我们还研究了针对 DKK3 或 CKAP4 的抗体是否可以抑制癌细胞的恶性潜能。
在大多数 OSCC 病例中观察到 DKK3/CKAP4 蛋白表达，并且与更高的 T 分期和 TNM 分期显著相关。多因素分析显示，DKK3 和 CKAP4 分别是总生存（OS）和无病生存（DFS）的独立预后生物标志物。生存分析显示，DKK3 阳性病例和 CKAP4 阳性病例的 OS 和 DFS 明显缩短，而 DKK3/CKAP4 双阴性病例的预后明显较好。抗 DKK3Ab 和抗 CKAP4Ab 均可抑制癌细胞的增殖、迁移和侵袭。
DKK3/CKAP4 轴在 OSCC 中被认为是重要的，它可能是一个有前途的治疗靶点。
