Chen Taiqin, Kim Ki-Yeol, Oh Yeongjoo, Jeung Hei Cheul, Chung Kee Yang, Roh Mi Ryung, Zhang Xianglan
Department of Dermatology, Yanbian University Hospital, Yanji 133000, China.
Department of Dental Education, BK21 PLuS Project, Yonsei University College of Dentistry, Seoul 03722, Korea.
Cancers (Basel). 2022 Apr 18;14(8):2038. doi: 10.3390/cancers14082038.
The underlying molecular mechanisms of cutaneous squamous cell carcinoma (cSCC) pathogenesis are largely unknown. In the present study, we aimed to evaluate the effect of coatomer protein complex subunit beta 2 (COPB2) expression on cSCC pathogenesis. Clinicopathological significance of COPB2 in cSCC was investigated by analyzing the Gene Expression Omnibus (GEO) database and through a retrospective cohort study of 95 cSCC patients. The effect of COPB2 expression on the biological behavior of cSCC cells was investigated both in vitro and in vivo. We found that COPB2 expression was significantly higher in cSCC samples than in normal skin samples. In our cohort, a considerable association was found between COPB2 expression and indicators of tumor immune microenvironment (TIME), such as histocompatibility complex class (MHC) I, and MHC II, CD4+/ CD8+ tumor-infiltrating lymphocytes. Additionally, COPB2 expression had an independent impact on worsened recurrence-free survival in our cohort. Furthermore, decreased proliferation, invasion, tumorigenic activities, and increased apoptosis were observed after knockdown in cSCC cells. COPB2 may act as a potential oncogene and candidate modulator of the TIME in cSCC. Therefore, it can serve as a novel predictive prognostic biomarker and candidate immunotherapeutic target in cSCC patients.
皮肤鳞状细胞癌（cSCC）发病机制的潜在分子机制在很大程度上尚不清楚。在本研究中，我们旨在评估外套膜蛋白复合物亚基β2（COPB2）表达对cSCC发病机制的影响。通过分析基因表达综合数据库（GEO）以及对95例cSCC患者进行回顾性队列研究，探讨了COPB2在cSCC中的临床病理意义。在体外和体内研究了COPB2表达对cSCC细胞生物学行为的影响。我们发现，cSCC样本中COPB2的表达明显高于正常皮肤样本。在我们的队列中，发现COPB2表达与肿瘤免疫微环境（TIME）指标之间存在显著关联，如组织相容性复合体I类（MHC）和MHC II、CD4+/CD8+肿瘤浸润淋巴细胞。此外，在我们的队列中，COPB2表达对无复发生存期恶化有独立影响。此外，在cSCC细胞中敲低COPB2后，观察到增殖、侵袭、致瘤活性降低，凋亡增加。COPB2可能作为cSCC中一种潜在的癌基因和TIME的候选调节因子。因此，它可作为cSCC患者一种新的预测性预后生物标志物和候选免疫治疗靶点。
