E353: Single cell transcriptomic analysis reveals differences between primary appendiceal tumors.

Appendiceal adenocarcinoma (AACa) are rare neoplasms of the appendix. Often diagnosed incidentally or at advanced stages when peritoneal dissemination has occurred. Current treatment guidelines for disseminated disease call for systemic chemotherapy versus cytoreductive surgery with heated intraperitoneal chemotherapy for selected surgical candidates. Nonetheless, the mechanisms responsible for AACa development and dissemination remain poorly understood. Using single cell transcriptomic analysis, we set out to characterize the tumoral epithelial cells of a patient with AACa with peritoneal dissemination.


Methods: Patients were consented under Stanford IRB protocols. Surgically removed tissue was minced and enzymatically dissociated to obtained single cell suspensions. These were used to construct cDNA transcriptomic libraries that were sequenced and analyzed using in-house developed bioinformatic pipelines. In this study, we compare the AACa patient to a cohort of patients with an appendiceal mucinous neoplasm without (AMN, n=3) and with pseudomyxoma peritonei (PMP, n=3) and primary colon cancer (n=1).

Results: We conducted analysis of a primary appendix AACa tumor and its small bowel mesentery metastasis using single cell transcriptomic libraries. Analysis of the AACa derived epithelial cells revealed a crypt or stem cell signature, especially when evaluating the metastatic tumor. This is in contrast with AMN/PMP tumors which have a goblet-cell like signature. Furthermore, comparison of AACa to our AMN/PMP cohort reveals differences in their cellularity, epithelial cell signatures and cellular & signaling pathways.

Conclusions: Our analysis demonstrate epithelial cell signatures differences between appendiceal mucinous and appendiceal adenocarcinoma tumors. importantly, comparison of the primary appendiceal tumors (AMN/PMP and AACa) and a primary colorectal tumor highlight differences in their cellularity, pathology and signaling mechanisms which may ultimately impact treatment strategies for these malignancies.