{"doi":"10.1101/2021.11.02.467008","title":"Wound-like tumor periphery in human breast cancer predicts a convergent drug nonresponse","abstract":"Abstract A significant portion of breast cancer patients are nonresponsive to well-established drugs and destined for a poor outcome regardless of molecular subtype. Although several (multiparameter) molecular markers have predicted their resistance to some of these drugs, profound uniparameter markers predictive of a convergent nonresponse to all these drugs remain elusive. We employ co-registered standard-multiphoton histology to representatively sample a few peripheral niches of the primary tumor, so that hundreds of patients can be stratified with either a wound-like or non-wound tumor periphery. With no fitting variable, this simple uniparameter morphological marker is: (a) highly sensitive and specific to predict a multidrug-nonresponsive phenotype that accounts for the majority of recurrence or death, independent of the molecular subtype or related adjuvant drug selection, clinical endpoint (disease-free versus overall survival), and hosting medical center; (b) robust against intratumor heterogeneity and valid at the earliest clinicopathological stage; and (c) dominant in predicting prognosis in the context of routine clinicopathological markers. Considering the mechanistic link between a wound-like extracellular matrix and a microenvironment supporting migratory or mesenchymal tumor cells, we attribute these unusual capabilities to an epithelial-mesenchymal transition nature of the morphological marker long sought after by pathologists.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221956,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":329647,"name":"Xiaoxia Liao","orcid":"0000-0003-2794-3044","position":1,"is_corresponding":false},{"id":822550,"name":"Fangmeng Fu","orcid":"0000-0002-3065-5708","position":2,"is_corresponding":false},{"id":822551,"name":"Gangqin Xi","orcid":"0000-0002-7888-4569","position":3,"is_corresponding":false},{"id":530162,"name":"Deyong Kang","orcid":"0009-0001-7357-3016","position":4,"is_corresponding":false},{"id":542264,"name":"Jiajia He","orcid":"0000-0003-0073-7689","position":5,"is_corresponding":false},{"id":708604,"name":"Wenhui Guo","orcid":"0000-0002-9177-8568","position":6,"is_corresponding":false},{"id":530991,"name":"Lida Qiu","orcid":null,"position":7,"is_corresponding":false},{"id":822552,"name":"Zhonghua Han","orcid":"0000-0002-2051-7504","position":8,"is_corresponding":false},{"id":822553,"name":"Xingfu Wang","orcid":"0000-0002-0734-4936","position":9,"is_corresponding":false},{"id":822554,"name":"Qingyuan Zhan","orcid":"0000-0003-0021-0270","position":10,"is_corresponding":false},{"id":417933,"name":"Sixian You","orcid":"0000-0002-1243-1815","position":11,"is_corresponding":false},{"id":530163,"name":"Jianxin Chen","orcid":"0000-0001-8519-4462","position":12,"is_corresponding":false},{"id":822555,"name":"Chuan Wang","orcid":"0000-0002-9742-9756","position":13,"is_corresponding":false},{"id":366688,"name":"Stephen A. Boppart","orcid":"0000-0002-9386-5630","position":14,"is_corresponding":false},{"id":417936,"name":"Haohua Tu","orcid":"0000-0003-3116-0149","position":15,"is_corresponding":false},{"id":530158,"name":"Lianhuang Li","orcid":"0000-0002-3531-6668","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:53:59.302331Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}