Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
J Surg Oncol. 2023 Mar;127(4):587-597. doi: 10.1002/jso.27140. Epub 2022 Nov 11.
Biliary tract cancers are rare, with a poor patient prognosis. Leptin and programmed death-ligand 1 (PD-L1) influence CD8 and forkhead box P3 (FOXP3) lymphocytes, and thus, cancer cell growth. We aimed to define the prognostic implications of these variables and the clinicopathological features of biliary tract cancers.
Immunohistochemistry for leptin signaling-related proteins (leptin, leptin receptor, pSTAT3, extracellular-regulated kinase, mammalian target of rapamycin), PD-L1, CD8, and FOXP3 and in situ hybridization for Epstein-Barr virus-encoded small RNAs were performed in 147 cases of surgically-resected biliary tract cancers.
Immune cell PD-L1-positivity, tumor size < 3 cm, adjuvant chemotherapy, no recurrence, and early-stage tumors were correlated with better 5-year survival in the tumoral PD-L1 and leptin subgroups, and extrahepatic cholangiocarcinoma through multivariate analysis (all p < 0.05). Immune cell PD-L1 and adjuvant chemotherapy lost its prognostic significance in the tumoral PD-L1 and leptin subgroups.
The prognostic implication of the variables may depend upon tumoral protein expression and the anatomical site. Immune cell PD-L1-positivity and the administration of adjuvant chemotherapy may indicate the favorable survival of patients with surgically-resected biliary tract cancers, specifically, in the tumoral PD-L1 or tumor leptin subgroups and extrahepatic cholangiocarcinoma. PD-L1- or leptin-targeted therapy combined with conventional chemotherapy may benefit the tumoral PD-L1 or leptin subgroups.
胆道癌较为罕见，患者预后较差。瘦素和程序性死亡配体 1（PD-L1）影响 CD8 和叉头框 P3（FOXP3）淋巴细胞，从而影响癌细胞生长。本研究旨在明确这些变量与胆道癌临床病理特征的预后意义。
对 147 例手术切除的胆道癌进行瘦素信号相关蛋白（瘦素、瘦素受体、pSTAT3、细胞外调节激酶、雷帕霉素靶蛋白）、PD-L1、CD8 和 FOXP3 的免疫组化和 Epstein-Barr 病毒编码的小 RNA 的原位杂交检测。
肿瘤 PD-L1 阳性、肿瘤直径<3cm、辅助化疗、无复发和早期肿瘤与肿瘤 PD-L1 和瘦素亚组中 tumoral PD-L1 和 leptin 患者的 5 年生存率较好相关，且通过多变量分析在肝外胆管癌中也具有统计学意义（均 p<0.05）。在肿瘤 PD-L1 和瘦素亚组中，免疫细胞 PD-L1 和辅助化疗失去了其预后意义。
这些变量的预后意义可能取决于肿瘤蛋白的表达和解剖部位。免疫细胞 PD-L1 阳性和辅助化疗可能提示手术切除的胆道癌患者具有较好的生存预后，特别是在 tumoral PD-L1 或肿瘤瘦素亚组和肝外胆管癌中。PD-L1 或瘦素靶向治疗联合常规化疗可能对 tumoral PD-L1 或肿瘤瘦素亚组有益。
