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pmid:35515127

Markers Associated With Tumor Recurrence in Patients With Breast Cancer Achieving a Pathologic Complete Response After Neoadjuvant Chemotherapy.

Li-Yun Xie · Kun Wang · Hai-Lu Chen · Yan-Xia Shi · Yuan-Qi Zhang · Hao-Yu Lin · Yuan-Ke Liang · Ying-Sheng Xiao · Zhi-Yong Wu · Zhong-Yu Yuan · Si-Qi Qiu

Frontiers in oncology · 2022 doi:10.3389/fonc.2022.860475

Paper

complete

Experiment

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Data

partial

Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:35515127
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science-record
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2026-11-01T18:14:24Z
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2026-11-01T22:06:27Z
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paper object · 10 fields
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title
Markers Associated With Tumor Recurrence in Patients With Breast Cancer Achieving a Pathologic Complete Response After Neoadjuvant Chemotherapy.
doi
10.3389/fonc.2022.860475
pmid
35515127
authors array · 11 items
[0]
Li-Yun Xie
[1]
Kun Wang
[2]
Hai-Lu Chen
[3]
Yan-Xia Shi
[4]
Yuan-Qi Zhang
[5]
Hao-Yu Lin
[6]
Yuan-Ke Liang
[7]
Ying-Sheng Xiao
[8]
Zhi-Yong Wu
[9]
Zhong-Yu Yuan
[10]
Si-Qi Qiu
journal
Frontiers in oncology
year
2022
abstract
Background: Patients who achieve a tumor pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better outcomes than patients with residual tumor. However, tumors still recur in the pCR patients. Therefore, we aim to explore factors associated with tumor recurrence in this patient population. Methods: A total of 1,913 patients diagnosed with breast cancer between 1995 and 2020 and received NAC were included in this analysis. Clinicopathological data of the patients were retrospectively collected. We used Cox regression analysis to assess the associations of clinicopathological factors with patients' outcome. Proteomic study of tumors was applied to identify differentially expressed proteins (DEPs) between tumors from the pCR patients with tumor recurrence and tumors from those without tumor recurrence. PPI network analysis of the corresponding genes of DEPs was used to identify the hub genes. The prognostic value of the corresponding genes of DEPs was evaluated using two online databases, Kaplan-Meier Plotter and bc-GenExMiner. The genes that were significantly associated with patients' survival in both databases, as well as being identified as hub genes, were considered as potential prognostic markers for pCR patients. Publicly available data from Gene Expression Omnibus (GEO) was used to verify the prognostic value of the identified marker. Results: Among the 1,913 included patients, 420 had tumor pCR. The median follow-up for the pCR patients was 32.6 months (IQR, 16.3-55.5). Overall estimated 5-year risk of tumor recurrence for the pCR patients was 11%. Multivariable analysis showed that a higher pre-NAC clinical T stage and N stage were independent predictors for increased risk of tumor recurrence (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.01-6.51, P=0.047 for clinical T stage and HR 3.48, 95%CI 1.37-8.83, P=0.009 for clinical N stage). NAC regimens, the type of breast and axillary surgery, and adjuvant chemotherapy were not associated with tumor recurrence. Finally, aldehyde dehydrogenase (ALDH) 3A2 was identified by the proteomic study and was verified as a potential predictor for tumor recurrence in the pCR patients (with a median follow up of 3.78 years for dataset GSE32603 and 2.74 years for dataset GSE25066 from GEO, tumor recurrence rate: low versus high expression, 20.7% versus 4.5% [data from GSE32603]; 10.9% versus 0% [data from GSE25066]). Conclusions: Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC.
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The prognostic value of clinicopathological factors was determined using univariable and multivariable Cox regression analyses.
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sections[9] "Statistical Analysis" paragraph 2
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The prognostic value of clinicopathological factors was determined using univariable and multivariable Cox regression analyses.
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The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
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sections[18] "Data Availability Statement" paragraph 2
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The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
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Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC.
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sections[0] "Abstract" paragraph 4
quote
Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC.
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Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC.
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https://doi.org/10.3389/fonc.2022.860475
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10.3389/fonc.2022.860475
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data:geo:GSE25066
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE25066
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The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
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96
taxon
Homo sapiens
title
Genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer
resolution_checked_at
2026-11-01T15:39:54Z
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The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
structure object · 15 fields
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access_statement_verbatim
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
access_statement_kind
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248
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14668
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Homo sapiens
title
Serial gene expression analysis in locally advanced breast cancer patients who failed to respond to neoadjuvant chemotherapy
resolution_checked_at
2026-11-01T17:30:42Z
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data object · 6 fields
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GSE32603
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GSE25066
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[0]
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
basis
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source:pmid:35515127
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[0]
l Hospital who participated in a multicentre phase III trial (NCT03006614), 113 patients from Central Peo
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[1] object · 11 fields
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[0]
here was evidence of protein overexpression (immunohistochemistry staining 3+) or gene amplification (fluoresc
[1]
terone receptor (PR) status, HER2 status and Ki67 expression. Positivity of ER, PR and HER2 we
[2]
number ≥ 6 signals/cell) (13). Low level of Ki67 expression was reported as percentage of cel
[3]
tive nuclei staining < 20% and high level of Ki67 expression as ≥ 20%. pCR was defined as no e
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paper_text_order:3937
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assay:2
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The prognostic value of clinicopathological factors was determined using univariable and multivariable Cox regression analyses.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35515127", "kind": "science-record", "revision": 4, "content_hash": "sha256:1b899a48311cca9ca3bcba0556f9c024115ff49da72118e12974a2692254583e", "created_at": "2026-11-01T18:14:24Z", "updated_at": "2026-11-01T22:06:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Markers Associated With Tumor Recurrence in Patients With Breast Cancer Achieving a Pathologic Complete Response After Neoadjuvant Chemotherapy.", "doi": "10.3389/fonc.2022.860475", "pmid": "35515127", "authors": ["Li-Yun Xie", "Kun Wang", "Hai-Lu Chen", "Yan-Xia Shi", "Yuan-Qi Zhang", "Hao-Yu Lin", "Yuan-Ke Liang", "Ying-Sheng Xiao", "Zhi-Yong Wu", "Zhong-Yu Yuan", "Si-Qi Qiu"], "journal": "Frontiers in oncology", "year": 2022, "abstract": "Background: Patients who achieve a tumor pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better outcomes than patients with residual tumor. However, tumors still recur in the pCR patients. Therefore, we aim to explore factors associated with tumor recurrence in this patient population.\nMethods: A total of 1,913 patients diagnosed with breast cancer between 1995 and 2020 and received NAC were included in this analysis. Clinicopathological data of the patients were retrospectively collected. We used Cox regression analysis to assess the associations of clinicopathological factors with patients' outcome. Proteomic study of tumors was applied to identify differentially expressed proteins (DEPs) between tumors from the pCR patients with tumor recurrence and tumors from those without tumor recurrence. PPI network analysis of the corresponding genes of DEPs was used to identify the hub genes. The prognostic value of the corresponding genes of DEPs was evaluated using two online databases, Kaplan-Meier Plotter and bc-GenExMiner. The genes that were significantly associated with patients' survival in both databases, as well as being identified as hub genes, were considered as potential prognostic markers for pCR patients. Publicly available data from Gene Expression Omnibus (GEO) was used to verify the prognostic value of the identified marker.\nResults: Among the 1,913 included patients, 420 had tumor pCR. The median follow-up for the pCR patients was 32.6 months (IQR, 16.3-55.5). Overall estimated 5-year risk of tumor recurrence for the pCR patients was 11%. Multivariable analysis showed that a higher pre-NAC clinical T stage and N stage were independent predictors for increased risk of tumor recurrence (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.01-6.51, P=0.047 for clinical T stage and HR 3.48, 95%CI 1.37-8.83, P=0.009 for clinical N stage). NAC regimens, the type of breast and axillary surgery, and adjuvant chemotherapy were not associated with tumor recurrence. Finally, aldehyde dehydrogenase (ALDH) 3A2 was identified by the proteomic study and was verified as a potential predictor for tumor recurrence in the pCR patients (with a median follow up of 3.78 years for dataset GSE32603 and 2.74 years for dataset GSE25066 from GEO, tumor recurrence rate: low versus high expression, 20.7% versus 4.5% [data from GSE32603]; 10.9% versus 0% [data from GSE25066]).\nConclusions: Clinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC.", "claims": [{"id": "claim-method", "statement": "The prognostic value of clinicopathological factors was determined using univariable and multivariable Cox regression analyses.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35515127", "locator": "sections[9] \"Statistical Analysis\" paragraph 2", "quote": "The prognostic value of clinicopathological factors was determined using univariable and multivariable Cox regression analyses."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35515127", "locator": "sections[18] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE25066"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE25066"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35515127", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2022.860475", "sha256": "sha256:d24b9eb3b158ebaf75f2cab6c4ec3e0a12ac7c0eb0c058abbd8cfdbec476f9fa", "bytes": 47687, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2022.860475", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9067275", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE25066", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE25066", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE25066", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. 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Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. 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