Yang Lewei, Zeng Qi, Deng Yun, Qiu Yeqing, Yao Wei, Liao Yifeng
Department of Oncology, The fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Front Oncol. 2022 Apr 13;12:876245. doi: 10.3389/fonc.2022.876245. eCollection 2022.
Dysregulation of cysteine cathepsin protease activity is pivotal in tumorigenic transformation. However, the role of cathepsin protease in lung cancer remains unknown. Here, we analyzed GEO database and found that lung cancer presented high expression of cathepsin V (). We then performed immunohistochemistry assay in 73 paired lung cancer tissues and normal lung tissues and confirmed that is overexpressed in lung cancer and correlates with poor prognosis. The mass spectrometry experiment showed that the N-glycosylation locus of are N221 and N292, glycosylated (band 43 kDa) was particularly expressed in lung cancer samples and correlated with lymph node metastasis. Mechanistic studies showed that only glycosylated (43-kDa band) are secreted to extracellular matrix (ECM) and promoted the metastasis of lung cancer. Importantly, the Elisa detection in serum of 12 lung cancer patients and 12 healthy donors showed that the level of in serum distinguished lung cancer patients from healthy donors. Together, our findings reveal the clinical relevance of glycosylation and drives the metastasis of lung cancer, suggesting that the glycosylated in serum is a promising biomarker for lung cancer.
半胱氨酸组织蛋白酶蛋白酶活性的失调在肿瘤发生转化中起关键作用。然而，组织蛋白酶蛋白酶在肺癌中的作用仍不清楚。在这里，我们分析了基因表达综合数据库（GEO数据库），发现肺癌中组织蛋白酶V呈现高表达。然后我们在73对肺癌组织和正常肺组织中进行了免疫组织化学检测，证实其在肺癌中过表达且与预后不良相关。质谱实验表明，其N-糖基化位点为N221和N292，糖基化的组织蛋白酶V（43 kDa条带）在肺癌样本中特别表达且与淋巴结转移相关。机制研究表明，只有糖基化的组织蛋白酶V（43 kDa条带）分泌到细胞外基质（ECM）并促进肺癌转移。重要的是，对12名肺癌患者和12名健康供体血清的酶联免疫吸附测定（ELISA）检测表明，血清中组织蛋白酶V的水平可区分肺癌患者和健康供体。总之，我们的研究结果揭示了组织蛋白酶V糖基化的临床相关性，并且其驱动肺癌转移，表明血清中糖基化的组织蛋白酶V是一种有前景的肺癌生物标志物。
