Aga Khan University Hospital, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.
J Cancer Res Clin Oncol. 2023 Jun;149(6):2279-2292. doi: 10.1007/s00432-022-04315-4. Epub 2022 Sep 6.
Pancreatic Ductal Adenocarcinoma (PDAC) is the most common type of pancreatic malignancies. It is known for its aggressive nature and high mortality rate. This calls for an urgent need of new prognostic and therapeutic markers that can be targeted for personalized treatment of the patient.
Among 142 patients diagnosed with pancreatic cancers at Aga Khan University Hospital, a total of 62 patients were selected based on their confirmed diagnosis of PDAC. Immunohistochemistry was performed on Formalin-Fixed Paraffin-Embedded (FFPE) sections using selected antibodies (CD44, CD133, L1CAM, HER2, PD-L1, EGFR, COX2 and cyclin D1). All the slides were scored independently by two pathologists as per the set criteria.
Expression of all cancer stem cell markers was found to be significantly associated with one or more potential therapeutic markers. CD44 expression was significantly associated with HER2 (p = 0.032), COX2 (p = 0.005) and EGFR expression (p = 0.008). CD133 expression also showed significant association with HER2 (p = 0.036), COX2 (p = 0.004) and EGFR expression (p = 0.018). L1CAM expression was found to be associated with expression of COX2 (p = 0.017). None of the proteins markers showed association with overall survival of the patient. On the other hand, among the clinicopathological characteristics, histological differentiation (p = 0.047), lymphovascular invasion (p = 0.021) and perineural invasion (p = 0.014) were found to be significantly associated with patient's overall survival.
Internationally, this is the first report that assesses the selected panel of cancer stem cell markers and potential therapeutic targets in a single study and evaluates its combined expression. The study clearly demonstrates association between expression of cancer stem cell markers and therapeutic targets hence paves a way for precision medicine for pancreatic cancer patients.
胰腺导管腺癌（PDAC）是最常见的胰腺恶性肿瘤。它以侵袭性强和死亡率高为特征。这就迫切需要新的预后和治疗标志物，以便针对患者进行个性化治疗。
在 Aga Khan 大学医院诊断为胰腺癌的 142 名患者中，根据他们确诊为 PDAC 的情况，共选择了 62 名患者。使用选定的抗体（CD44、CD133、L1CAM、HER2、PD-L1、EGFR、COX2 和细胞周期蛋白 D1）对福尔马林固定石蜡包埋（FFPE）切片进行免疫组织化学染色。两位病理学家根据设定的标准独立对所有切片进行评分。
所有癌症干细胞标志物的表达均与一种或多种潜在治疗性标志物显著相关。CD44 的表达与 HER2（p=0.032）、COX2（p=0.005）和 EGFR 表达（p=0.008）显著相关。CD133 的表达也与 HER2（p=0.036）、COX2（p=0.004）和 EGFR 表达（p=0.018）显著相关。L1CAM 的表达与 COX2 的表达相关（p=0.017）。没有一种蛋白质标志物与患者的总生存率相关。另一方面，在临床病理特征中，组织学分化（p=0.047）、血管淋巴管侵犯（p=0.021）和神经周围侵犯（p=0.014）与患者的总生存率显著相关。
在国际上，这是首次评估单个研究中选定的癌症干细胞标志物和潜在治疗靶点，并评估其联合表达的报告。该研究清楚地表明，癌症干细胞标志物的表达与治疗靶点之间存在关联，为胰腺癌患者的精准医学铺平了道路。
