This preprint is under consideration at World Journal of Surgical Oncology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research Article
Henghui Zhang
Capital Medical University Affiliated Beijing Ditan Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2820-7447
License:
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Background: HER2-positive breast cancer (BC) is a highly aggressive phenotype and accounts for 15–20% of all BC cases. The role of the host immune features in predictive response to anti-HER2 therapies and prognosis in BC is already suggested. We aimed to develop a predictive and prognostic model and examine its relevance to the clinical outcomes of patients with HER2-positive BC.
Methods: Based on the single-sample gene set enrichment analysis (ssGSEA) scores of the signatures related to neoadjuvant trastuzumab therapy response, an immune effective score (IES) was constructed using principal component analysis algorithms. A bioinformatic analysis using 4 independent cohorts (GSE66305, n=88; GSE130786, n=110; TCGA, n=123; METABRIC, n=236) established associations between IES and clinical outcomes.
Results: Genes associated with neoadjuvant trastuzumab therapy response enriched in pathways related to antitumor immune activities, including T cell receptor signaling pathway, Natural killer cell-mediated cytotoxicity and NF−kappa B signaling pathway. IES was demonstrated to be a predictive biomarker to neoadjuvant trastuzumab therapy benefits (GSE66305: area under the curve (AUC) = 0.804; GSE130786: AUC = 0.704). In addition, IES was identified as an independent prognostic factor for overall survival (OS) in the TCGA cohort (P = 0.036, hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.449–0.97) and METABRIC cohort (P = 0.037, HR: 0.9, 95% CI: 0.81–0.99).
Conclusions: The IES has a predictive value for response to neoadjuvant trastuzumab therapy and independent prognostic value for HER2-positive breast cancer.
Keywords
HER2-positive breast cancer, neoadjuvant, trastuzumab, pathological complete response, prognosis
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This is a list of supplementary files associated with this preprint. Click to download.
- TableS1.docx
- figureS1.pdf
Figure S1 Predictive analysis of IES. Bar plots depict the clinical response rate to neoadjuvant chemo+lapatinib therapy in high or low IES groups in the GSE66305 cohort (A) and GSE130786 cohort (C). Bar plots depict the clinical response rate to neoadjuvant chemo+lapatinib+trastuzumab therapy in high or low IES groups in the GSE66305 cohort (B) and GSE130786 cohort (D). pCR: complete response; RD: residual disease.
- figureS2.pdf
Figure S2 Prognostic analysis of the IES in the METABRIC cohort. Forest plots of multivariate Cox regression proportional hazards regression analysis of OS in the METABRIC cohort (A). P-value was calculated by cox regression (* P < 0.05, ** P < 0.01, *** P < 0.001). OS: overall survival. Kaplan-Meier survival curves showed the OS stratified by low/high-IES in the METABRIC cohort (B). P values were obtained by the log-rank test.
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This preprint is under consideration at World Journal of Surgical Oncology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Henghui Zhang
Capital Medical University Affiliated Beijing Ditan Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2820-7447
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 18 Mar, 2021
No community comments so far
Review #1 received
Received 01 Apr, 2021
Reviewer #1 agreed
On 18 Mar, 2021
Editor assigned
On 08 Mar, 2021
Reviewers invited
Invitations sent on 08 Mar, 2021
Submission checks complete
On 07 Mar, 2021
Editor invited
On 07 Mar, 2021
First submitted
On 04 Mar, 2021
No comments provided
Editorial decision: Reject before peer review
On 02 Oct, 2020
Editor assigned
On 29 Sep, 2020
Editor invited
On 28 Sep, 2020
Submission checks complete
On 27 Sep, 2020
First submitted
On 25 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: HER2-positive breast cancer (BC) is a highly aggressive phenotype and accounts for 15–20% of all BC cases. The role of the host immune features in predictive response to anti-HER2 therapies and prognosis in BC is already suggested. We aimed to develop a predictive and prognostic model and examine its relevance to the clinical outcomes of patients with HER2-positive BC.
Methods: Based on the single-sample gene set enrichment analysis (ssGSEA) scores of the signatures related to neoadjuvant trastuzumab therapy response, an immune effective score (IES) was constructed using principal component analysis algorithms. A bioinformatic analysis using 4 independent cohorts (GSE66305, n=88; GSE130786, n=110; TCGA, n=123; METABRIC, n=236) established associations between IES and clinical outcomes.
Results: Genes associated with neoadjuvant trastuzumab therapy response enriched in pathways related to antitumor immune activities, including T cell receptor signaling pathway, Natural killer cell-mediated cytotoxicity and NF−kappa B signaling pathway. IES was demonstrated to be a predictive biomarker to neoadjuvant trastuzumab therapy benefits (GSE66305: area under the curve (AUC) = 0.804; GSE130786: AUC = 0.704). In addition, IES was identified as an independent prognostic factor for overall survival (OS) in the TCGA cohort (P = 0.036, hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.449–0.97) and METABRIC cohort (P = 0.037, HR: 0.9, 95% CI: 0.81–0.99).
Conclusions: The IES has a predictive value for response to neoadjuvant trastuzumab therapy and independent prognostic value for HER2-positive breast cancer.
Figure 1
Figure 2
Figure 3
Figure 4
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