DKK3/CKAP4 axis is associated with advanced stage and poorer prognosis in oral cancer

被引：10

作者：

Katase, Naoki ^{[1
]}

Kudo, Kodai ^{[1
,2
]}

Ogawa, Kazuhiro ^{[1
,2
]}

Sakamoto, Yae ^{[1
,2
]}

Nishimatsu, Shin-ichiro ^{[3
]}

Yamauchi, Akira ^{[4
]}

Fujita, Shuichi ^{[1
]}

机构：

[1] Nagasaki Univ, Inst Biomed Sci, Dept Oral Pathol, 1-7-1 Sakamoto, Nagasaki 8528588, Japan

[2] Nagasaki Univ, Dent Sch, Nagasaki, Japan

[3] Kawasaki Med Sch, Dept Nat Sci, Okayama, Japan

[4] Kawasaki Med Sch, Dept Biochem, Okayama, Japan

来源：

ORAL DISEASES | 2023年 / 29卷 / 08期

关键词：

CKAP4; DKK3; head and neck cancer; oral squamous cell carcinoma; SQUAMOUS-CELL CARCINOMA; PROTEIN; 4; DICKKOPF (DKK)-3; EXPRESSION; HEAD; DKK3; METASTASIS; KNOCKDOWN; RECEPTOR;

D O I：

10.1111/odi.14277

中图分类号：

R78 [口腔科学];

学科分类号：

1003 ;

摘要：

Objective 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. Methods 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. Results 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. Conclusion DKK3/CKAP4 axis is thought to be important in OSCC, and it would be a promising therapeutic target.

引用

页码：3193 / 3204

页数：12

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