Single-cell sequencing identifies differentiation-related markers for molecular classification and recurrence prediction of PitNET

Summary

Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors with variable recurrence rate. Currently, the recurrence prediction is unsatisfying and can be improved by understanding the cellular origins and differentiation status. Here, to comprehensively reveal the origin of PitNET, we perform comparative analysis of single-cell RNA sequencing data from 3 anterior pituitary glands and 21 PitNETs. We identify distinct genes representing major subtypes of well and poorly differentiated PitNETs in each lineage. To further verify the predictive value of differentiation biomarkers, we include an independent cohort of 800 patients with an average follow-up of 7.2 years. In both PIT1 and TPIT lineages, poorly differentiated groups show significantly higher recurrence rates while well-differentiated groups show higher recurrence rates in SF1 lineage. Our findings reveal the possible origin and differentiation status of PitNET based on which new differentiation classification is proposed and verified to predict tumor recurrence.

Graphical abstract

Highlights

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  Trajectory analysis in the APG reveals a progenitor PIT1 lineage cluster

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  The comparative analysis evaluates the differentiation status of PitNET

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  The differentiation-related markers could help predict the long-term recurrence

Abstract

Zhang et al. provide a comparative analysis between anterior pituitary glands (APGs) and pituitary neuroendocrine tumors (PitNETs) at single-cell resolution. The differentiation status of PitNETs is evaluated, and the recurrence prediction values of differentiation-related markers are validated in an independent cohort of 800 patients.