Kurihara-Shimomura Miyako, Sasahira Tomonori, Nakamura Hiroshi, Nakashima Chie, Kuniyasu Hiroki, Kirita Tadaaki
Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Japan.
Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
J Clin Pathol. 2018 May;71(5):436-441. doi: 10.1136/jclinpath-2017-204770. Epub 2017 Oct 26.
Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common cancer worldwide and has a high potential for locoregional invasion and nodal metastasis. Therefore, discovery of a useful molecular biomarker capable of predicting tumour progression and metastasis of OSCC is crucial. We have previously reported zinc finger AN1-type containing 4 (ZFAND4) as one of the most upregulated genes in recurrent OSCC using a cDNA microarray analysis. Although ZFAND4 has been shown to promote cell proliferation of gastric cancer, its expression and clinicopathological roles in OSCC remain unclear.
In this study, we examined ZFAND4 expression by immunohistochemistry in 214 cases of OSCC.
High cytoplasmic expression of ZFAND4 was observed in 45 out of 214 (21%) patients with OSCC. Expression levels of ZFAND4 were strongly associated with metastasis to the lymph nodes (p=0.0429) and distant organs (p=0.0068). Cases with high expression of ZFAND4 had a significantly unfavourable prognosis compared with patients with low expression of ZFAND4 (p<0.0001). Furthermore, ZFAND4 overexpression was an independent poor prognostic factor for OSCC as determined by multivariate analysis using the Cox proportional hazards model (p<0.0001).
These results suggest that ZFAND4 is a useful marker for predicting metastasis and poor prognosis in patients with OSCC.
头颈癌，包括口腔鳞状细胞癌（OSCC），是全球第六大常见癌症，具有较高的局部区域侵袭和淋巴结转移潜力。因此，发现一种能够预测OSCC肿瘤进展和转移的有用分子生物标志物至关重要。我们之前通过cDNA微阵列分析报道过含锌指AN1型4（ZFAND4）是复发性OSCC中上调最明显的基因之一。尽管已证明ZFAND4可促进胃癌细胞增殖，但其在OSCC中的表达及临床病理作用仍不清楚。
在本研究中，我们通过免疫组织化学检测了214例OSCC病例中ZFAND4的表达。
在214例（21%）OSCC患者中，有45例观察到ZFAND4的高细胞质表达。ZFAND4的表达水平与淋巴结转移（p = 0.0429）和远处器官转移（p = 0.0068）密切相关。与ZFAND4低表达患者相比，ZFAND4高表达患者的预后明显较差（p < 0.0001）。此外，使用Cox比例风险模型进行多变量分析确定，ZFAND4过表达是OSCC独立的不良预后因素（p < 0.0001）。
这些结果表明，ZFAND4是预测OSCC患者转移和不良预后的有用标志物。
