Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, University School of Medicine, Cardiff, U.K.
Gastrointestinal Cancer Centre, Peking University Cancer Hospital and Institute and Key Laboratory of Carcinogenesis, Beijing, P.R. China.
Anticancer Res. 2023 Apr;43(4):1463-1475. doi: 10.21873/anticanres.16295.
BACKGROUND/AIM: Activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, has been shown to regulate cell adhesion through both homotypic and heterotypic interactions. In cancer, it might be involved in disease progression and chemotherapy drug resistance. The present study explored the clinical and prognostic significance of ALCAM in gastric cancer and its impact on patient's responses to neoadjuvant chemotherapies and cancer cells' response to chemodrugs in vitro.
Two independent cohorts were included to evaluate the link between ALCAM and the clinical outcomes and pathological factors of the patients. The gastric cancer cell lines HGC27 and AGS were used to generate ALCAM knockdown cell models. The cytotoxicity of chemotherapy drugs was examined using ALCAM knockdown cell models.
Patients with gastric cancer who had high levels of ALCAM transcripts showed a significantly shorter overall survival in both cohorts (p=0.043 and 0.006, respectively). Patients who resisted to neoadjuvant chemotherapy had marginally higher levels of ALCAM than those responded (p=0.056). Patients with low levels of ALCAM expression and resisted to neoadjuvant chemotherapy had the worst clinical outcome with a significantly shorter overall survival (p=0.004) and disease-free survival (p=0.006), whereas such results did not appear in high ALCAM expression patients. ALCAM knockdown cells were more sensitive to Cisplatin, Oxaliplatin and 5-Fluorouracil compared with their respective control cells.
ALCAM acts as a negative prognostic indicator in patients with gastric cancer and high levels of ALCAM expression result in increased chemotherapy drug resistance.
背景/目的：活化白细胞细胞黏附分子（ALCAM/CD166）是免疫球蛋白超家族的成员，已被证明通过同质和异质相互作用来调节细胞黏附。在癌症中，它可能参与疾病进展和化疗药物耐药。本研究探讨了 ALCAM 在胃癌中的临床和预后意义及其对患者对新辅助化疗反应和癌细胞对体外化疗药物反应的影响。
纳入两个独立队列评估 ALCAM 与患者临床结局和病理因素之间的关系。使用胃癌细胞系 HGC27 和 AGS 生成 ALCAM 敲低细胞模型。使用 ALCAM 敲低细胞模型检查化疗药物的细胞毒性。
两个队列中，ALCAM 转录本水平高的胃癌患者总生存期明显缩短（p=0.043 和 0.006）。对新辅助化疗有抵抗的患者的 ALCAM 水平略高于有反应的患者（p=0.056）。ALCAM 低表达且对新辅助化疗有抵抗的患者的临床结局最差，总生存期（p=0.004）和无病生存期（p=0.006）明显缩短，而高 ALCAM 表达患者则没有出现这种情况。与相应的对照细胞相比，ALCAM 敲低细胞对顺铂、奥沙利铂和 5-氟尿嘧啶更敏感。
ALCAM 是胃癌患者的负预后指标，高水平的 ALCAM 表达导致化疗药物耐药性增加。
