Prasad Nijaguna B, Fischer Anne C, Chuang Alice Y, Wright Jerry M, Yang Ting, Tsai Hua-Ling, Westra William H, Liegeois Nanette J, Hess Allan D, Tufaro Anthony P
Department of Plastic and Reconstructive Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
Mod Pathol. 2014 Jul;27(7):945-57. doi: 10.1038/modpathol.2013.217. Epub 2013 Dec 20.
Although the cure rate for cutaneous squamous cell carcinoma is high, the diverse spectrum of squamous cell carcinoma has made it difficult for early diagnosis, particularly the aggressive tumors that are highly associated with mortality. Therefore, molecular markers are needed as an adjunct to current staging methods for diagnosing high-risk lesions, and stratifying those patients with aggressive tumors. To identify such biomarkers, we have examined a comprehensive set of 200 histologically defined squamous cell carcinoma and normal skin samples by using a combination of microarray, QRT-PCR and immunohistochemistry analyses. A characteristic and distinguishable profile including matrix metalloproteinase (MMP) as well as other degradome components was differentially expressed in squamous cell carcinoma compared with normal skin samples. The expression levels of some of these genes including matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 10 (MMP10), parathyroid hormone-like hormone (PTHLH), cyclin-dependent kinase inhibitor 2A (CDKN2A), A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), FBJ osteosarcoma oncogene (FOS), interleukin 6 (IL6) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) were significantly differentially expressed (P≤0.02) in squamous cell carcinoma compared with normal skin. Furthermore, based on receiver operating characteristic analyses, the mRNA and protein levels of MMP1 are significantly higher in aggressive tumors compared with non-aggressive tumors. Given that MMPs represent the most prominent family of proteinases associated with tumorigenesis, we believe that they may have an important role in modulating the tumor microenvironment of squamous cell carcinoma.
虽然皮肤鳞状细胞癌的治愈率很高，但鳞状细胞癌的多样性使得早期诊断变得困难，尤其是那些与死亡率高度相关的侵袭性肿瘤。因此，需要分子标志物作为当前分期方法的辅助手段，用于诊断高危病变，并对那些患有侵袭性肿瘤的患者进行分层。为了识别此类生物标志物，我们通过结合微阵列、定量逆转录聚合酶链反应（QRT-PCR）和免疫组织化学分析，对一组全面的200个组织学定义的鳞状细胞癌和正常皮肤样本进行了检测。与正常皮肤样本相比，包括基质金属蛋白酶（MMP）以及其他降解组成分在内的一种特征性且可区分的图谱在鳞状细胞癌中差异表达。其中一些基因的表达水平，包括基质金属肽酶1（MMP1）、基质金属肽酶10（MMP10）、甲状旁腺激素样激素（PTHLH）、细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）、含血小板反应蛋白基序的解聚素和金属蛋白酶1（ADAMTS1）、FBJ骨肉瘤癌基因（FOS）、白细胞介素6（IL6）和含kazal基序的富含半胱氨酸的逆转诱导蛋白（RECK），在鳞状细胞癌中与正常皮肤相比有显著差异表达（P≤0.02）。此外，基于受试者工作特征分析，与非侵袭性肿瘤相比，侵袭性肿瘤中MMP1的mRNA和蛋白水平显著更高。鉴于MMPs是与肿瘤发生相关的最突出的蛋白酶家族，我们认为它们可能在调节鳞状细胞癌的肿瘤微环境中起重要作用。
