A Novel Serum-Based Bioassay for Quantification of Cancer-Associated Transformation Activity: A Case–Control and Animal Study

<b>Background/Objectives</b>: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell li...

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Main Authors: Aye Aye Khine, Hsuan-Shun Huang, Pao-Chu Chen, Chun-Shuo Hsu, Ying-Hsi Chen, Sung-Chao Chu, Tang-Yuan Chu
Format: Article
Language:English
Published: MDPI AG 2025-08-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/15/15/1975
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author Aye Aye Khine
Hsuan-Shun Huang
Pao-Chu Chen
Chun-Shuo Hsu
Ying-Hsi Chen
Sung-Chao Chu
Tang-Yuan Chu
author_facet Aye Aye Khine
Hsuan-Shun Huang
Pao-Chu Chen
Chun-Shuo Hsu
Ying-Hsi Chen
Sung-Chao Chu
Tang-Yuan Chu
author_sort Aye Aye Khine
collection DOAJ
description <b>Background/Objectives</b>: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. <b>Methods</b>: Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. <b>Results</b>: TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, <i>p</i> < 0.01) and correlated with serum CA125 levels (<i>r</i> = 0.73, <i>p</i> = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden (<i>r</i> = 0.95, <i>p</i> < 0.01). <b>Conclusions</b>: Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation.
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spelling doaj-art-e74f7a8e256447eaa9046195bb667de72025-08-20T03:36:03ZengMDPI AGDiagnostics2075-44182025-08-011515197510.3390/diagnostics15151975A Novel Serum-Based Bioassay for Quantification of Cancer-Associated Transformation Activity: A Case–Control and Animal StudyAye Aye Khine0Hsuan-Shun Huang1Pao-Chu Chen2Chun-Shuo Hsu3Ying-Hsi Chen4Sung-Chao Chu5Tang-Yuan Chu6Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien Tzu Chi Hospital, Hualien 97004, TaiwanCenter for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien Tzu Chi Hospital, Hualien 97004, TaiwanDepartment of Obstetrics & Gynecology, Hualien Tzu Chi Hospital, Hualien 97004, TaiwanDepartment of Obstetrics & Gynecology, Dalin Tzu Chi Hospital, Dalin 90749, TaiwanDepartment of Obstetrics & Gynecology, Hualien Tzu Chi Hospital, Hualien 97004, TaiwanDepartment of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, TaiwanCenter for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan<b>Background/Objectives</b>: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. <b>Methods</b>: Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. <b>Results</b>: TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, <i>p</i> < 0.01) and correlated with serum CA125 levels (<i>r</i> = 0.73, <i>p</i> = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden (<i>r</i> = 0.95, <i>p</i> < 0.01). <b>Conclusions</b>: Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation.https://www.mdpi.com/2075-4418/15/15/1975cancer diagnosisanchorage-independent growthblood testbiological assayovarian neoplasms
spellingShingle Aye Aye Khine
Hsuan-Shun Huang
Pao-Chu Chen
Chun-Shuo Hsu
Ying-Hsi Chen
Sung-Chao Chu
Tang-Yuan Chu
A Novel Serum-Based Bioassay for Quantification of Cancer-Associated Transformation Activity: A Case–Control and Animal Study
Diagnostics
cancer diagnosis
anchorage-independent growth
blood test
biological assay
ovarian neoplasms
title A Novel Serum-Based Bioassay for Quantification of Cancer-Associated Transformation Activity: A Case–Control and Animal Study
title_full A Novel Serum-Based Bioassay for Quantification of Cancer-Associated Transformation Activity: A Case–Control and Animal Study
title_fullStr A Novel Serum-Based Bioassay for Quantification of Cancer-Associated Transformation Activity: A Case–Control and Animal Study
title_full_unstemmed A Novel Serum-Based Bioassay for Quantification of Cancer-Associated Transformation Activity: A Case–Control and Animal Study
title_short A Novel Serum-Based Bioassay for Quantification of Cancer-Associated Transformation Activity: A Case–Control and Animal Study
title_sort novel serum based bioassay for quantification of cancer associated transformation activity a case control and animal study
topic cancer diagnosis
anchorage-independent growth
blood test
biological assay
ovarian neoplasms
url https://www.mdpi.com/2075-4418/15/15/1975
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