Evidence map›Paper›PMID 34905486›Full record

ArticleeLife2021

Single-cell transcriptome analysis identifies a unique tumor cell type producing multiple hormones in ectopic ACTH and CRH secreting pheochromocytoma.

Xuebin Zhang, Penghu Lian, Mingming Su, Zhigang Ji, Jianhua Deng, Guoyang Zheng, Wenda Wang, Xinyu Ren, Taijiao Jiang, Peng Zhang and 1 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.

  1. Ectopic ACTH Syndrome Caused by Pheochromocytoma: A Case Report and Systematic Review.Endocrine, metabolic & immune disorders drug targets · 2026
    Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Utility ofIrish veterinary journal · 2025
    Article
  9. Single-Cell Atlas Reveals Tumorigenic Profiles and Immune Dynamics of Adrenal Incidentalomas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  10. Review
  11. Article
  12. Article
  13. [Endothelial cells and fibroblasts mediate the microenvironmental regulatory network of carotid body paraganglioma].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2024
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. New Biology of Pheochromocytoma and Paraganglioma.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Xuebin Zhang *Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Penghu Lian *Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Mingming Su *Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.ORCID 0000-0002-1393-0800
Zhigang JiDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Jianhua DengDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Guoyang ZhengDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Wenda WangDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Xinyu RenDepartment of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Taijiao JiangInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Peng ZhangBeijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.ORCID 0000-0002-6218-1885
Hanzhong LiDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Chinese Academy of Medical Sciences & Peking Union Medical College · CNCapital Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ectopic Cushing's syndrome due to ectopic ACTH&CRH-secreting by pheochromocytoma is extremely rare and can be fatal if not properly diagnosed. It remains unclear whether a unique cell type is responsible for multiple hormones secreting. In this work, we performed single-cell RNA sequencing to three different anatomic tumor tissues and one peritumoral tissue based on a rare case with ectopic ACTH&CRH-secreting pheochromocytoma. And in addition to that, three adrenal tumor specimens from common pheochromocytoma and adrenocortical adenomas were also involved in the comparison of tumor cellular heterogeneity. A total of 16 cell types in the tumor microenvironment were identified by unbiased cell clustering of single-cell transcriptomic profiles from all specimens. Notably, we identified a novel multi-functionally chromaffin-like cell type with high expression of both POMC (the precursor of ACTH) and CRH, called ACTH+&CRH + pheochromocyte. We hypothesized that the molecular mechanism of the rare case harbor Cushing's syndrome is due to the identified novel tumor cell type, that is, the secretion of ACTH had a direct effect on the adrenal gland to produce cortisol, while the secretion of CRH can indirectly stimulate the secretion of ACTH from the anterior pituitary. Besides, a new potential marker (GAL) co-expressed with ACTH and CRH might be involved in the regulation of ACTH secretion. The immunohistochemistry results confirmed its multi-functionally chromaffin-like properties with positive staining for CRH, POMC, ACTH, GAL, TH, and CgA. Our findings also proved to some extent the heterogeneity of endothelial and immune microenvironment in different adrenal tumor subtypes.

Indexed as

TranscriptomeACTH Syndrome, EctopicAdrenal Gland NeoplasmsAdrenocorticotropic HormoneCorticotropin-Releasing HormoneGene Expression ProfilingPheochromocytomaSingle-Cell AnalysisAdrenocorticotropic HormoneCorticotropin-Releasing Hormoneadrenal tumorcancer biologycell biologyCRH secreting pheochromocytomacushing syndromeectopic ACTHhumanscRNA-seq

Identifiers

PMID34905486
PMCPMC8719890
OpenAlexW4200137381

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.