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Main Authors: Fan, Wenqi, Zhang, Dengwei, Li, Yuqing, Wang, Haiyan, Li, Yong-Xin, Li, Bin, Zou, Shien, Feng, Chenchen, Guo, Ting
Format: Artículo científico
Language:en
Published: FEMS microbiology letters 2025
Subjects:
Online Access:https://pubmed.ncbi.nlm.nih.gov/41032321/
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author Fan, Wenqi
Zhang, Dengwei
Li, Yuqing
Wang, Haiyan
Li, Yong-Xin
Li, Bin
Zou, Shien
Feng, Chenchen
Guo, Ting
author_facet Fan, Wenqi
Zhang, Dengwei
Li, Yuqing
Wang, Haiyan
Li, Yong-Xin
Li, Bin
Zou, Shien
Feng, Chenchen
Guo, Ting
Fan, Wenqi
Zhang, Dengwei
Li, Yuqing
Wang, Haiyan
Li, Yong-Xin
Li, Bin
Zou, Shien
Feng, Chenchen
Guo, Ting
collection PubMed - marine biology
contents Intratumoral fungus Neurospora crassa is associated with worsened prognosis in ovarian cancer via modulation of extracellular matrix. Fan, Wenqi Zhang, Dengwei Li, Yuqing Wang, Haiyan Li, Yong-Xin Li, Bin Zou, Shien Feng, Chenchen Guo, Ting Neurospora crassa Mycoses Prognosis Ovarian Neoplasms Humans Female Animals Mice Cell Line, Tumor Extracellular Matrix Eosinophils Landmark studies on intratumoral fungi (ITF) have raised concerns due to irreproducible results and data-analysis errors. We aimed to determine whether ITF exist in ovarian cancer (OvCa) and, if so, whether they play a role in disease biology. Formalin-fixed, paraffin-embedded OvCa samples and multiple controls underwent operational decontamination, qPCR, internal transcribed spacer sequencing, and post-hoc data decontamination. We also leveraged updated fungal reads from The Cancer Genome Atlas generated by the TCMbio group, which addressed human-read contamination and artificial inflation, to validate findings and assess prognostic associations. A murine syngeneic model established using mouse ovarian cancer cell line (OVHM) with intratumoral Neurospora crassa injection was established. Transcriptomic and metabolomic analyses were performed to explore mechanisms. Tumor-containing blocks harbored significantly higher fungal loads than environmental controls but had loads comparable to paraffin controls. Applying a two-pass decontamination filter reduced raw sequence features from 9289 amplicon sequence variants (ASVs) to 659 ASVs. We focused on high-abundance features present in human tissues but absent from xenografts and paraffin controls and identified one candidate, N. crassa, associated with unfavorable prognosis in OvCa. Integrating human and murine data, we found Neurospora correlated with eosinophils, whereas N. crassa itself was not immune-related. Neurospora crassa promoted OvCa progression with downregulation of integrin-linked kinase and decreased extracellular matrix-receptor interaction. Most ITF signals are likely contaminants. We identified N. crassa as associated with unfavorable prognosis in OvCa, potentially via modulation of the extracellular matrix.
format Artículo científico
id pubmed_41032321
institution PubMed
language en
publishDate 2025
publisher FEMS microbiology letters
record_format pubmed
spellingShingle Intratumoral fungus Neurospora crassa is associated with worsened prognosis in ovarian cancer via modulation of extracellular matrix.
Fan, Wenqi
Zhang, Dengwei
Li, Yuqing
Wang, Haiyan
Li, Yong-Xin
Li, Bin
Zou, Shien
Feng, Chenchen
Guo, Ting
Neurospora crassa
Mycoses
Prognosis
Ovarian Neoplasms
Humans
Female
Animals
Mice
Cell Line, Tumor
Extracellular Matrix
Eosinophils
Intratumoral fungus Neurospora crassa is associated with worsened prognosis in ovarian cancer via modulation of extracellular matrix. Fan, Wenqi Zhang, Dengwei Li, Yuqing Wang, Haiyan Li, Yong-Xin Li, Bin Zou, Shien Feng, Chenchen Guo, Ting Neurospora crassa Mycoses Prognosis Ovarian Neoplasms Humans Female Animals Mice Cell Line, Tumor Extracellular Matrix Eosinophils Landmark studies on intratumoral fungi (ITF) have raised concerns due to irreproducible results and data-analysis errors. We aimed to determine whether ITF exist in ovarian cancer (OvCa) and, if so, whether they play a role in disease biology. Formalin-fixed, paraffin-embedded OvCa samples and multiple controls underwent operational decontamination, qPCR, internal transcribed spacer sequencing, and post-hoc data decontamination. We also leveraged updated fungal reads from The Cancer Genome Atlas generated by the TCMbio group, which addressed human-read contamination and artificial inflation, to validate findings and assess prognostic associations. A murine syngeneic model established using mouse ovarian cancer cell line (OVHM) with intratumoral Neurospora crassa injection was established. Transcriptomic and metabolomic analyses were performed to explore mechanisms. Tumor-containing blocks harbored significantly higher fungal loads than environmental controls but had loads comparable to paraffin controls. Applying a two-pass decontamination filter reduced raw sequence features from 9289 amplicon sequence variants (ASVs) to 659 ASVs. We focused on high-abundance features present in human tissues but absent from xenografts and paraffin controls and identified one candidate, N. crassa, associated with unfavorable prognosis in OvCa. Integrating human and murine data, we found Neurospora correlated with eosinophils, whereas N. crassa itself was not immune-related. Neurospora crassa promoted OvCa progression with downregulation of integrin-linked kinase and decreased extracellular matrix-receptor interaction. Most ITF signals are likely contaminants. We identified N. crassa as associated with unfavorable prognosis in OvCa, potentially via modulation of the extracellular matrix.
title Intratumoral fungus Neurospora crassa is associated with worsened prognosis in ovarian cancer via modulation of extracellular matrix.
topic Neurospora crassa
Mycoses
Prognosis
Ovarian Neoplasms
Humans
Female
Animals
Mice
Cell Line, Tumor
Extracellular Matrix
Eosinophils
url https://pubmed.ncbi.nlm.nih.gov/41032321/