Zhang Xue, Sun Mengfei, Li Na, Yu Jie, Wang Wenjie, Yang Ju, Wu Hongyan, Zhao Linyue, Zhang Huakun, Yang Lan, Li Feng, Sun Qi, Chen Yunzhao, Cui Xiaobin
Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Cancer Center of Suining Central Hospital, Suining, China.
Cancer Sci. 2025 Sep;116(9):2592-2606. doi: 10.1111/cas.70128. Epub 2025 Jun 30.
Esophageal squamous cell carcinoma (ESCC) has a significantly low survival rate, primarily due to the lack of diagnostic markers for early diagnosis and effective therapies. Recently, CD98 has been proposed as a specific marker of mature esophageal basal cells, which may be associated with esophageal carcinogenesis. Therefore, we aimed to investigate the clinical significance and biological function of CD98 in ESCC progression, as well as the value of CD98 as a potential new marker for the early diagnosis of ESCC. Through MassARRAY system spectroscopy, DIA proteomics analysis, immunohistochemical and functional experiments, we found hypomethylation-linked upregulation of CD98 expression, which was associated with poor prognosis, promoted cell proliferation by regulating the cell cycle in ESCC. Furthermore, we not only demonstrated that the range of CD98 expression was consistent with that of dysplastic cells in 73.81% of low-grade intraepithelial neoplasia (LGIN) and 83.08% of high-grade intraepithelial neoplasia (HGIN) cases, but also confirmed the expression level of CD98 was positively correlated with the classical diagnosis marker P53. Compared to using P53 alone, the combination of the immunohistochemical markers CD98 and P53 (either one was positive) provided more accurate diagnostic data for LGIN (92.86% vs. 88.10%, p < 0.01) and HGIN (93.85% vs. 73.85%, p < 0.01). In summary, we propose that CD98 is involved in a crucial step in ESCC carcinogenesis, and when combined with P53, may serve as a diagnostic marker for ESCC precancerous lesions.
食管鳞状细胞癌（ESCC）的生存率极低，主要原因是缺乏用于早期诊断的诊断标志物和有效的治疗方法。最近，CD98被认为是成熟食管基底细胞的特异性标志物，这可能与食管癌发生有关。因此，我们旨在研究CD98在ESCC进展中的临床意义和生物学功能，以及CD98作为ESCC早期诊断潜在新标志物的价值。通过MassARRAY系统光谱分析、DIA蛋白质组学分析、免疫组织化学和功能实验，我们发现CD98表达的低甲基化相关上调与预后不良有关，通过调节ESCC中的细胞周期促进细胞增殖。此外，我们不仅证明在73.81%的低级别上皮内瘤变（LGIN）和83.08%的高级别上皮内瘤变（HGIN）病例中，CD98的表达范围与发育异常细胞的一致，还证实CD98的表达水平与经典诊断标志物P53呈正相关。与单独使用P53相比，免疫组织化学标志物CD98和P53（任一为阳性）的组合为LGIN（92.86%对88.10%，p<0.01）和HGIN（93.85%对73.85%，p<0.01）提供了更准确的诊断数据。总之，我们提出CD98参与了ESCC致癌过程中的关键步骤，并且与P53联合使用时，可能作为ESCC癌前病变的诊断标志物。
