Mucinous Balls Tangled With Mesothelial Cells and MUC2‐Positive Cancer Cells in the Ascites of Pseudomyxoma Peritonei

Akashi, C T Shizuka; Kuwabara, Hiroko; Yasuda, Emi; Akutagawa, Hiroshi; Takeshita, Atsushi; Kurisu, Yoshitaka; Egashira, Yasuyuki; Hirose, Yoshinobu; Yuki, Masako; Tsuda, Yasuhiro; Hayashi, Michihiro

doi:10.1002/dc.23486

Cited by 1 publication

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References 8 publications

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“…The mass spectrometric analysis of patient derived ascites identified MUC2, AGR2 and MUC5AC in all the tested patients. This is consistent with prior IHC and western blot assays detecting MUC2 and MUC5AC in PMP tissue and ascites [71, 72]. Furthermore, we detected a heterogenous composition of mucins in our scRNA-seq analysis for patients in the AMN and PMP cohorts, with MUC2 and MUC5AC detected consistently in all patients.…”

Section: Discussionsupporting

confidence: 90%

Distinct cell states define the developmental trajectories of mucinous appendiceal neoplasms towards pseudomyxoma metastases

Ayala

Sathe

Bai

et al. 2022

Preprint

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Objective: Appendiceal mucinous neoplasms (AMN) start in the appendix. Following appendiceal perforation, these tumor metastasize, leading to pseudomyxoma peritonei (PMP). We characterized the distinct cell types and states of AMN and PMP. Design: Single-cell RNA-seq was conducted on 31 samples including AMNs, PMP metastases and a subset of matched normal appendix or omental tissues. We validated the findings with immunohistochemistry, mass spectrometry on malignant ascites from PMP patients and gene expression data from an independent set of 63 PMPs. Results: AMNs and PMPs had epithelial tumor cells with goblet features including the elevated expression of mucin genes. Among these tumors, we identified developmental cell states of the epithelium that ranged from progenitor phase to goblet cell differentiation. Metastatic PMP cells had a distinct cell state with gene expression signatures indicative of mTOR and RAS signaling pathways. A series of cancer genes defined this metastatic cell state. Matched PMP metastases from the same patient differed in their expression signatures. The cell state signatures were validated in external datasets containing 63 PMP patients. AMN and PMP tumor microenvironment (TME) contained CD4 T follicular helper-like cells and cytotoxic CD8 T cells. Conclusion: AMN and PMP tumors consisted of progenitor epithelial cells that differentiate into goblet cells. PMP cells had a distinct cell state indicative of metastasis. The TME was infiltrated with T cells, suggesting that immunotherapy is a potential treatment.

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Section: Discussionsupporting

confidence: 90%