Viculin Jelena, Degoricija Marina, Vilović Katarina, Gabela Ivana, Franković Lucija, Vrdoljak Eduard, Korac-Prlic Jelena
Department of Oncology and Radiotherapy, University Hospital of Split, 21000 Split, Croatia.
Department of Medical Chemistry and Biochemistry, School of Medicine, University of Split, 21000 Split, Croatia.
Cancers (Basel). 2023 Jul 5;15(13):3510. doi: 10.3390/cancers15133510.
Laryngeal cancer is the second most common malignancy of the head and neck, worldwide. Immunotherapy targeting checkpoint inhibitors has been approved for the treatment of patients with recurrent or metastatic laryngeal cancer but has a relatively low response rate and outcomes that leave many patients underserved. Targeting the cGAS-STING signaling pathway can potentially improve the activation of immune effector cells, although its role in the development and progression of laryngeal cancer has not yet been investigated in depth. Fifty-nine tumor samples from patients with pathologically confirmed squamous cell carcinoma of the larynx, stage I-IV non-metastatic disease, who were treated at the University Hospital of Split, were immunohistochemically stained for the expression of STING, cGAS, CD8, CD68, and CD163. Elevated tumor cell-intrinsic STING expression was positively associated with stage IV ( = 0.0031), pT3, and pT4 laryngeal cancers ( = 0.0336) as well as with higher histological grades (G2 and G3) ( = 0.0204) and lymph node-positive tumors ( = 0.0371). After adjusting for age, sex, location, and cGAS expression, elevated STING expression was significantly associated with stage IV cancer in a multiple logistic regression model (β = 1.849, SE = ±0.8643, = 0.0324). Elevated STING expression represents a potentially favorable predictive biomarker for new therapeutic approaches involving STING agonists combined with immunotherapy and DNA-damaging agents (radiotherapy, cisplatin, and PARP inhibitors) in laryngeal cancer.
喉癌是全球范围内头颈部第二常见的恶性肿瘤。针对检查点抑制剂的免疫疗法已被批准用于治疗复发或转移性喉癌患者，但该疗法的缓解率相对较低，许多患者的治疗效果不佳。靶向cGAS-STING信号通路可能会增强免疫效应细胞的激活，尽管其在喉癌发生和发展中的作用尚未得到深入研究。对来自斯普利特大学医院、患有病理确诊的I-IV期非转移性喉鳞状细胞癌的59例患者的肿瘤样本进行免疫组织化学染色，以检测STING、cGAS、CD8、CD68和CD163的表达。肿瘤细胞内STING表达升高与IV期喉癌（P=0.0031）、pT3和pT4期喉癌（P=0.0336）、更高的组织学分级（G2和G3）（P=0.0204）以及淋巴结阳性肿瘤（P=0.0371）呈正相关。在调整年龄、性别、肿瘤位置和cGAS表达后，在多元逻辑回归模型中，STING表达升高与IV期癌症显著相关（β=1.849，标准误=±0.8643，P=0.0324）。STING表达升高代表了一种潜在的有利预测生物标志物，可用于涉及STING激动剂联合免疫疗法和DNA损伤剂（放疗、顺铂和PARP抑制剂）治疗喉癌的新治疗方法。
