Evidence map›Paper›PMID 22618571›Full record

ArticleThe oncologist2012

A second-generation microRNA-based assay for diagnosing tumor tissue origin.

Eti Meiri, Wolf C Mueller, Shai Rosenwald, Merav Zepeniuk, Elizabeth Klinke, Tina Bocker Edmonston, Margot Werner, Ulrike Lass, Iris Barshack, Meora Feinmesser and 11 more

Abstract readValidation Study
In one paragraph

Article in The oncologist, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

76 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. SEOM-GETTHI clinical guideline for the practical management of molecular platforms (2021).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
    Guideline
  2. Pooled it
  3. Trial
  4. SEOM‑GETTHI clinical guideline for the practical management of molecular platforms (update 2026).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. IsomiR stoichiometry changes as disease biomarkers.Molecular therapy. Nucleic acids · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Prostate cancer biomarkers: from early diagnosis to precision treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Review
  14. A Journey to Reach the Ovary Using Next-Generation Technologies.International journal of molecular sciences · 2023
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

16 more citing papers are in PubMed but not listed here.

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

21 authors.

Eti MeiriRosetta Genomics, Rehovot, Israel.
Wolf C Mueller
Shai Rosenwald
Merav Zepeniuk
Elizabeth Klinke
Tina Bocker Edmonston
Margot Werner
Ulrike Lass
Iris Barshack
Meora Feinmesser
Monica Huszar
Franz Fogt
Karin Ashkenazi
Mats Sanden
Eran Goren
Nir Dromi
Orit Zion
Ilanit Burnstein
Ayelet Chajut
Yael Spector
Ranit Aharonov

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCancers of unknown primary origin (CUP) constitute 3%-5% (50,000 to 70,000 cases) of all newly diagnosed cancers per year in the United States. Including cancers of uncertain primary origin, the total number increases to 12%-15% (180,000 to 220,000 cases) of all newly diagnosed cancers per year in the United States. Cancers of unknown/uncertain primary origins present major diagnostic and clinical challenges because the tumor tissue of origin is crucial for selecting optimal treatment. MicroRNAs are a family of noncoding, regulatory RNA genes involved in carcinogenesis. MicroRNAs that are highly stable in clinical samples and tissue specific serve as ideal biomarkers for cancer diagnosis. Our first-generation assay identified the tumor of origin based on 48 microRNAs measured on a quantitative real-time polymerase chain reaction platform and differentiated 25 tumor types.

methodsWe present here the development and validation of a second-generation assay that identifies 42 tumor types using a custom microarray. A combination of a binary decision-tree and a k-nearest-neighbor classifier was developed to identify the tumor of origin based on the expression of 64 microRNAs.

resultsOverall assay sensitivity (positive agreement), measured blindly on a validation set of 509 independent samples, was 85%. The sensitivity reached 90% for cases in which the assay reported a single answer (>80% of cases). A clinical validation study on 52 true CUP patients showed 88% concordance with the clinicopathological evaluation of the patients.

conclusionThe abilities of the assay to identify 42 tumor types with high accuracy and to maintain the same performance in samples from patients clinically diagnosed with CUP promise improved utility in the diagnosis of cancers of unknown/uncertain primary origins.

Indexed as

Gene Expression Regulation, NeoplasticAdultAgedAged, 80 and overBiological AssayBiomarkers, TumorDecision TreesFemaleGene Expression ProfilingHumansMaleMicroRNAsMiddle AgedNeoplasms, Unknown PrimaryReal-Time Polymerase Chain ReactionSensitivity and SpecificityBiomarkers, TumorMicroRNAs

Identifiers

PMID22618571
PMCPMC3380879

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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.