Xuzhou Clinical School, Xuzhou Medical University, Xuzhou, China.
Department of Otolaryngology-Head and Neck Surgery, Xuzhou Central Hospital, Xuzhou, China.
Front Endocrinol (Lausanne). 2022 Oct 10;13:1031210. doi: 10.3389/fendo.2022.1031210. eCollection 2022.
Laryngeal cancer (LC) is a prevalent head and neck malignancy; however, the essential pathophysiological mechanism underlying its tumorigenesis and progression remains elusive. Due to the perduring scarcity of effective targeted drugs for laryngeal cancer, insights into the disease's pathophysiological mechanisms would substantially impact the treatment landscape of laryngeal cancer.
To ensure quality consistency, 10 tumor and 9 non-tumor samples underwent proteomic analysis on a single mass spectrometer using a label-free technique. Subsequently, gene expression variations between laryngeal squamous cell carcinoma and normal tissues were analyzed using The Cancer Genome Atlas (TCGA) database. Immunohistochemical expressions of insulin-like growth factor 2 receptor (IGF2R), fibronectin (FN), vimentin, and α-smooth muscle actin (SMA) in LC tissues and normal tissues were determined.
In the tumor group, significant variations were detected for 433 upregulated and 61 downregulated proteins. Moreover, the heatmap revealed that the expressions of RNA translation-related proteins and proteins involved in RNA metabolism, such as IGF2R, tenascin C (TNC), periostin (POSTN), proteasome 26S subunit ATPase 4 (PSMC4), serpin family A member 3 (SERPINA3), heat shock protein family B (small) member 6 (HSPB6), osteoglycin (OGN), chaperonin containing TCP1 subunit 6A (CCT6A), and chaperonin containing TCP1 subunit 6B (CCT6B), were prominently elevated in the tumor group. Nonsense-mediated RNA decay (NMD), RNA translation, and protein stability were significantly altered in LC tumors. IGF2R was remarkably upregulated in LC tumors. In the TCGA database, the IGF2R mRNA level was significantly upregulated in LSCC tissues. Additionally, IGF2R mRNA expression was lowest in clinical grade 1 samples, with no significant difference between grades 2 and 3. In LSCC patients, a significant positive correlation between IGF2R expression and the stromal score was detected using the ESTIMATE algorithm to estimate the immune score, stromal score, and tumor purity in the tumor microenvironment. Lastly, immunohistochemical analysis revealed that IGF2R is overexpressed in LC.
These results demonstrate the vital role of IGF2R in LC carcinogenesis and progression and may facilitate the identification of new therapeutic targets for the prevention and treatment of LC.
喉癌（LC）是一种常见的头颈部恶性肿瘤；然而，其肿瘤发生和进展的基本病理生理机制仍难以捉摸。由于目前缺乏有效的喉癌靶向药物，因此深入了解疾病的病理生理机制将极大地影响喉癌的治疗格局。
为确保质量一致性，对 10 个肿瘤和 9 个非肿瘤样本在单个质谱仪上使用无标记技术进行蛋白质组分析。随后，使用癌症基因组图谱（TCGA）数据库分析喉鳞状细胞癌和正常组织之间的基因表达差异。在 LC 组织和正常组织中，通过免疫组织化学方法检测胰岛素样生长因子 2 受体（IGF2R）、纤连蛋白（FN）、波形蛋白和α-平滑肌肌动蛋白（SMA）的表达。
在肿瘤组中，检测到 433 个上调和 61 个下调蛋白的显著变化。此外，热图显示 IGF2R、tenascin C（TNC）、periostin（POSTN）、蛋白酶体 26S 亚基 ATPase 4（PSMC4）、丝氨酸蛋白酶家族 A 成员 3（SERPINA3）、热休克蛋白家族 B（小）成员 6（HSPB6）、骨连接蛋白（OGN）、含 TCP1 亚基的伴侣蛋白 6A（CCT6A）和含 TCP1 亚基的伴侣蛋白 6B（CCT6B）等与 RNA 翻译和 RNA 代谢相关的蛋白质的表达明显升高。在 LC 肿瘤中，非依赖性 RNA 衰变（NMD）、RNA 翻译和蛋白质稳定性显著改变。IGF2R 在 LC 肿瘤中明显上调。在 TCGA 数据库中，LSCC 组织中 IGF2R 的 mRNA 水平显著上调。此外，在临床分级 1 样本中 IGF2RmRNA 表达最低，2 级和 3 级之间无显著差异。在 LSCC 患者中，使用 ESTIMATE 算法估计肿瘤微环境中的免疫评分、基质评分和肿瘤纯度，发现 IGF2R 表达与基质评分之间存在显著正相关。最后，免疫组织化学分析显示 IGF2R 在 LC 中过度表达。
这些结果表明 IGF2R 在 LC 癌发生和进展中起着重要作用，并可能有助于识别预防和治疗 LC 的新治疗靶点。
