Cheng Jane J, Matsumoto Yasuyuki, Dombek Gabrielle E, Stackhouse Kathryn A, Ore Ana Sofia, Glickman Jonathan N, Heimburg-Molinaro Jamie, Cummings Richard D
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, CLS-11090, Boston, MA, 02115, USA.
FDA/CDER/OBQ/OBP/DBRRIII, Silver Spring, MD, USA.
Sci Rep. 2025 Feb 4;15(1):4177. doi: 10.1038/s41598-025-86988-8.
Alterations in protein glycosylation are observed in many solid tumor types leading to formation of tumor-associated carbohydrate antigens (TACAs). The most common TACA is the Tn antigen (CD175), which is a mucin-type O-GalNAc-Ser/Thr/Tyr glycan in membrane and secreted glycoproteins. In addition, two other TACAs are CA19-9 (sialyl-Lewis a), which is used as a prognostic serum marker for pancreatic cancer, and its isomer sialyl-Lewis x (SLex, CD15s), which is overexpressed in many cancer types and associated with metastasis. While CD175 and other TACAs may be expressed by many human carcinomas, little is known about their differential expression patterns in tumors, thus limiting their use as tissue biomarkers or therapeutic targets. Here we address the clinicopathological relevance of the expression of CA19-9, CD15s, and CD175 in pancreatic ductal adenocarcinoma (PDAC) tissues. Semi-quantitative IHC staining with well-defined monoclonal antibodies demonstrates that CD175 is expressed in all PDAC specimens analyzed. Unexpectedly, however, these TACAs are differentially expressed within PDAC specimens and their glycoproteins, but not significantly expressed in adjacent normal tissues. These data provide avenues for novel therapeutic approaches that could combine CD175- and CA19-9-targeting therapies for PDAC patients.
在许多实体瘤类型中都观察到蛋白质糖基化的改变，这会导致肿瘤相关碳水化合物抗原（TACAs）的形成。最常见的TACA是Tn抗原（CD175），它是一种存在于膜和分泌糖蛋白中的粘蛋白型O-连接的N-乙酰半乳糖胺-丝氨酸/苏氨酸/酪氨酸聚糖。此外，另外两种TACA是CA19-9（唾液酸化刘易斯a），它被用作胰腺癌的预后血清标志物，以及其异构体唾液酸化刘易斯x（SLex，CD15s），它在许多癌症类型中过表达并与转移相关。虽然CD175和其他TACAs可能在许多人类癌症中表达，但关于它们在肿瘤中的差异表达模式知之甚少，因此限制了它们作为组织生物标志物或治疗靶点的应用。在此，我们探讨了CA19-9、CD15s和CD175在胰腺导管腺癌（PDAC）组织中表达的临床病理相关性。使用明确的单克隆抗体进行的半定量免疫组化染色表明，CD175在所分析的所有PDAC标本中均有表达。然而，出乎意料的是，这些TACAs在PDAC标本及其糖蛋白中存在差异表达，但在相邻正常组织中无明显表达。这些数据为新的治疗方法提供了途径，这些方法可以将针对PDAC患者的CD175靶向疗法和CA19-9靶向疗法结合起来。
