ArticleBMC cancer2022
Combining gene expression analysis of gastric cancer cell lines and tumor specimens to identify biomarkers for anti-HER therapies-the role of HAS2, SHB and HBEGF.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02305043 (Identification of Biomarkers for Prediction of Response or Resistance Against Target Therapy in Adenocarcinoma of the Stomach or Gastroesophageal Junction. A Non-interventional Study), which is not on this map. Cited by 9 papers.
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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.
Identification of Biomarkers for Prediction of Response or Resistance Against Target Therapy in Adenocarcinoma of the Stomach or Gastroesophageal Junction. A Non-interventional Study
Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Pyrotinib Plus Trastuzumab as an Effective Later-Line Therapeutic Strategy for HER2-Positive Metastatic Colorectal Cancer: Results from a Phase II Study.Drug design, development and therapy · 2025Trial
- Comprehensive Analysis of Glycosyltransferase-Related Genes Reveals their Prognostic and Therapeutic Implications in Stomach Adenocarcinoma.Current protein & peptide science · 2026Article
- HER2DX ERBB2 score in advanced HER2-positive gastric cancer treated with trastuzumab and chemotherapy.ESMO open · 2025Article
- Review
- Obesity-Dependent Association of the rs10454142Biomedicines · 2024Article
- Three possible diagnostic biomarkers for gastric cancer: miR-362-3p, miR-362-5p and miR-363-5p.Biomarkers in medicine · 2024Article
- Quantitative proteomics profiling reveals the inhibition of trastuzumab antitumor efficacy by phosphorylated RPS6 in gastric carcinoma.Cancer chemotherapy and pharmacology · 2023Article
- Genetic and immune microenvironment characterization of HER2-positive gastric cancer: Their association with response to trastuzumab-based treatment.Cancer medicine · 2023Article
- alpha2,3 sialic acid processing enzymes expression in gastric cancer tissues reveals that ST3Gal3 but not Neu3 are associated with Lauren's classification, angiolymphatic invasion and histological grade.European journal of histochemistry : EJH · 2022Article
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe standard treatment for patients with advanced HER2-positive gastric cancer is a combination of the antibody trastuzumab and platin-fluoropyrimidine chemotherapy. As some patients do not respond to trastuzumab therapy or develop resistance during treatment, the search for alternative treatment options and biomarkers to predict therapy response is the focus of research. We compared the efficacy of trastuzumab and other HER-targeting drugs such as cetuximab and afatinib. We also hypothesized that treatment-dependent regulation of a gene indicates its importance in response and that it can therefore be used as a biomarker for patient stratification.
methodsA selection of gastric cancer cell lines (Hs746T, MKN1, MKN7 and NCI-N87) was treated with EGF, cetuximab, trastuzumab or afatinib for a period of 4 or 24 h. The effects of treatment on gene expression were measured by RNA sequencing and the resulting biomarker candidates were tested in an available cohort of gastric cancer patients from the VARIANZ trial or functionally analyzed in vitro.
resultsAfter treatment of the cell lines with afatinib, the highest number of regulated genes was observed, followed by cetuximab and trastuzumab. Although trastuzumab showed only relatively small effects on gene expression, BMF, HAS2 and SHB could be identified as candidate biomarkers for response to trastuzumab. Subsequent studies confirmed HAS2 and SHB as potential predictive markers for response to trastuzumab therapy in clinical samples from the VARIANZ trial. AREG, EREG and HBEGF were identified as candidate biomarkers for treatment with afatinib and cetuximab. Functional analysis confirmed that HBEGF is a resistance factor for cetuximab.
conclusionBy confirming HAS2, SHB and HBEGF as biomarkers for anti-HER therapies, we provide evidence that the regulation of gene expression after treatment can be used for biomarker discovery.
trial registrationClinical specimens of the VARIANZ study (NCT02305043) were used to test biomarker candidates.
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