Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma.
BACKGROUND:The current classification of human lung adenocarcinoma defines five different histological growth patterns within the group of conventional invasive adenocarcinomas. The five growth patterns are characterised by their typical architecture, but also by variable tumor biological behaviour....
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6198952?pdf=render |
| _version_ | 1818854957602832384 |
|---|---|
| author | Heike Zabeck Hendrik Dienemann Hans Hoffmann Joachim Pfannschmidt Arne Warth Philipp A Schnabel Thomas Muley Michael Meister Holger Sültmann Holger Fröhlich Ruprecht Kuner Felix Lasitschka |
| author_facet | Heike Zabeck Hendrik Dienemann Hans Hoffmann Joachim Pfannschmidt Arne Warth Philipp A Schnabel Thomas Muley Michael Meister Holger Sültmann Holger Fröhlich Ruprecht Kuner Felix Lasitschka |
| author_sort | Heike Zabeck |
| collection | DOAJ |
| description | BACKGROUND:The current classification of human lung adenocarcinoma defines five different histological growth patterns within the group of conventional invasive adenocarcinomas. The five growth patterns are characterised by their typical architecture, but also by variable tumor biological behaviour. AIMS:The aim of this study was to identify specific gene signatures of the five adenocarcinoma growth patterns defined by the joint IASLC/ATS/ERS working group. METHODS:Total RNA from microdissected adenocarcinoma tissue samples of ten lepidic, ten acinar, ten solid, nine papillary, and nine micropapillary tumor portions was isolated and prepared for gene expression analysis. Differential expression of genes was determined using the R package "LIMMA". The overall significance of each signature was assessed via global test. Gene ontology statistics were analysed using GOstat. For immunohistochemical validation, tissue specimens from 20 tumors with solid and 20 tumors with lepidic growth pattern were used. RESULTS:Microarray analyses between the growth patterns resulted in numerous differentially expressed genes between the solid architecture and other patterns. The comparison of transcriptomic activity in the solid and lepidic patterns revealed 705 up- and 110 downregulated non-redundant genes. The pattern-specific protein expression of Inositol-1,4,5-trisphosphate-kinase-A (ITPKA) and angiogenin by immunohistochemistry confirmed the RNA levels. The strongest differences in protein expression between the two patterns were shown for ITPKA (p = 0.02) and angiogenin (p = 0.113). CONCLUSIONS:In this study growth pattern-specific gene signatures in pulmonary adenocarcinoma were identified and distinct transcriptomic differences between lung adenocarcinoma growth patterns were defined. The study provides valuable new information about pulmonary adenocarcinoma and allows a better assessment of the five adenocarcinoma subgroups. |
| first_indexed | 2024-12-19T08:00:58Z |
| format | Article |
| id | doaj.art-4ff071dab405416fa1f0c589a0a03db9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T08:00:58Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4ff071dab405416fa1f0c589a0a03db92022-12-21T20:29:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011310e020613210.1371/journal.pone.0206132Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma.Heike ZabeckHendrik DienemannHans HoffmannJoachim PfannschmidtArne WarthPhilipp A SchnabelThomas MuleyMichael MeisterHolger SültmannHolger FröhlichRuprecht KunerFelix LasitschkaBACKGROUND:The current classification of human lung adenocarcinoma defines five different histological growth patterns within the group of conventional invasive adenocarcinomas. The five growth patterns are characterised by their typical architecture, but also by variable tumor biological behaviour. AIMS:The aim of this study was to identify specific gene signatures of the five adenocarcinoma growth patterns defined by the joint IASLC/ATS/ERS working group. METHODS:Total RNA from microdissected adenocarcinoma tissue samples of ten lepidic, ten acinar, ten solid, nine papillary, and nine micropapillary tumor portions was isolated and prepared for gene expression analysis. Differential expression of genes was determined using the R package "LIMMA". The overall significance of each signature was assessed via global test. Gene ontology statistics were analysed using GOstat. For immunohistochemical validation, tissue specimens from 20 tumors with solid and 20 tumors with lepidic growth pattern were used. RESULTS:Microarray analyses between the growth patterns resulted in numerous differentially expressed genes between the solid architecture and other patterns. The comparison of transcriptomic activity in the solid and lepidic patterns revealed 705 up- and 110 downregulated non-redundant genes. The pattern-specific protein expression of Inositol-1,4,5-trisphosphate-kinase-A (ITPKA) and angiogenin by immunohistochemistry confirmed the RNA levels. The strongest differences in protein expression between the two patterns were shown for ITPKA (p = 0.02) and angiogenin (p = 0.113). CONCLUSIONS:In this study growth pattern-specific gene signatures in pulmonary adenocarcinoma were identified and distinct transcriptomic differences between lung adenocarcinoma growth patterns were defined. The study provides valuable new information about pulmonary adenocarcinoma and allows a better assessment of the five adenocarcinoma subgroups.http://europepmc.org/articles/PMC6198952?pdf=render |
| spellingShingle | Heike Zabeck Hendrik Dienemann Hans Hoffmann Joachim Pfannschmidt Arne Warth Philipp A Schnabel Thomas Muley Michael Meister Holger Sültmann Holger Fröhlich Ruprecht Kuner Felix Lasitschka Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma. PLoS ONE |
| title | Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma. |
| title_full | Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma. |
| title_fullStr | Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma. |
| title_full_unstemmed | Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma. |
| title_short | Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma. |
| title_sort | molecular signatures in iaslc ats ers classified growth patterns of lung adenocarcinoma |
| url | http://europepmc.org/articles/PMC6198952?pdf=render |
| work_keys_str_mv | AT heikezabeck molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT hendrikdienemann molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT hanshoffmann molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT joachimpfannschmidt molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT arnewarth molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT philippaschnabel molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT thomasmuley molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT michaelmeister molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT holgersultmann molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT holgerfrohlich molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT ruprechtkuner molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma AT felixlasitschka molecularsignaturesiniaslcatsersclassifiedgrowthpatternsoflungadenocarcinoma |