Evidence map›Paper›PMID 36505794›Full record

ArticleFrontiers in oncology2022

Integrated spatial analysis of gene mutation and gene expression for understanding tumor diversity in formalin-fixed paraffin-embedded lung adenocarcinoma.

Miki Yamazaki, Masahito Hosokawa, Hiroko Matsunaga, Koji Arikawa, Kazuya Takamochi, Kenji Suzuki, Takuo Hayashi, Hideki Kambara, Haruko Takeyama

Open access · goldAbstract read
In one paragraph

Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 49% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
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

9 authors at 3 institutions in 1 country.

Miki YamazakiDepartment of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan.
Masahito HosokawaDepartment of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan.
Hiroko MatsunagaResearch Organization for Nano and Life Innovation, Waseda University, Tokyo, Japan.
Koji ArikawaResearch Organization for Nano and Life Innovation, Waseda University, Tokyo, Japan.
Kazuya TakamochiDepartment of Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Kenji SuzukiDepartment of Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Takuo HayashiDepartment of Human Pathology, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Hideki KambaraResearch Organization for Nano and Life Innovation, Waseda University, Tokyo, Japan.
Haruko TakeyamaDepartment of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan.
Waseda University · JPJuntendo University · JPNational Institute of Advanced Industrial Science and Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: A deeper understanding of intratumoral heterogeneity is essential for prognosis prediction or accurate treatment plan decisions in clinical practice. However, due to the cross-links and degradation of biomolecules within formalin-fixed paraffin-embedded (FFPE) specimens, it is challenging to analyze them. In this study, we aimed to optimize the simultaneous extraction of mRNA and DNA from microdissected FFPE tissues (φ = 100 µm) and apply the method to analyze tumor diversity in lung adenocarcinoma before and after erlotinib administration. Method: Two magnetic beads were used for the simultaneous extraction of mRNA and DNA. The decross-linking conditions were evaluated for gene mutation and gene expression analyses of microdissected FFPE tissues. Lung lymph nodes before treatment and lung adenocarcinoma after erlotinib administration were collected from the same patient and were preserved as FFPE specimens for 4 years. Gene expression and gene mutations between histologically classified regions of lung adenocarcinoma (pre-treatment tumor in lung lymph node biopsies and post-treatment tumor, normal lung, tumor stroma, and remission stroma, in resected lung tissue) were compared in a microdissection-based approach. Results: Using the optimized simultaneous extraction of DNA and mRNA and whole-genome amplification, we detected approximately 4,000-10,000 expressed genes and the epidermal growth factor receptor (EGFR) driver gene mutations from microdissected FFPE tissues. We found the differences in the highly expressed cancer-associated genes and the positive rate of EGFR exon 19 deletions among the tumor before and after treatment and tumor stroma, even though they were collected from tumors of the same patient or close regions of the same specimen. Conclusion: Our integrated spatial analysis method would be applied to various FFPE pathology specimens providing area-specific gene expression and gene mutation information.

Indexed as

cancer therapydrug resistanceformalin-fixed paraffin-embedded specimensintratumoral heterogeneity (ITH)non-small cell lung cancer (NSCLC)spatial transcriptometumor microenvironmenttyrosine-kinase inhibitors (TKIs)

Identifiers

PMID36505794
PMCPMC9731154
OpenAlexW4309920813

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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.