Pancreatic cancer stem cells may define tumor stroma characteristics and recurrence patterns in pancreatic ductal adenocarcinoma

BMC Cancer

Ibrahim Halil. Sahin¹  Aslihan Yavas²  Joanne F. Chou²  Gokce Askan²  Marinela Capanu²  Olca Basturk³  Christine A. Iacobuzio-Donahue³  Eileen M. O’Reilly⁴ 

[1]H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

[2]Memorial Sloan Kettering Cancer Center, 300 East 66th street, office 1021, 10065, New York, NY, USA

[3]Memorial Sloan Kettering Cancer Center, 300 East 66th street, office 1021, 10065, New York, NY, USA

[4]David M. Rubenstein Center for Pancreatic Cancer, New York, USA

[5]Memorial Sloan Kettering Cancer Center, 300 East 66th street, office 1021, 10065, New York, NY, USA

[6]David M. Rubenstein Center for Pancreatic Cancer, New York, USA

[7]Weill Cornell Medical College, New York, USA

关键词: Pancreatic ductal adenocarcinoma;    Pancreatic cancer;    Cancer stem cells;    Tumor stroma;    Sonic hedgehog;    Desmoplasia;    Tumor microenvironment;    CD44;    ESA;    Recurrence pattern;   

DOI  :  10.1186/s12885-021-08123-w

来源: Springer

【 摘 要 】

BackgroundHerein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients.MethodsPDAC patients who underwent surgical resection between 01/2012–06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher’s exact test.ResultsN = 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA− had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44−/ESA+ (35%), CD44−/ESA− (9%) (p = 0.0033). Conversely, lack of CD44 and ESA expression was associated with the highest rate of moderate and dense stroma (91% p = 0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence was observed in patients with loose stroma. No statistically significant difference in RFS and OS was observed among subgroups (P = 0.089).ConclusionsThese data indicate PCSCs may have an important role in stroma differentiation in PDAC. Our results further suggest that tumor stroma may influence the recurrence pattern in PDAC patients.

【 授权许可】

CC BY