Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women
Background: Since human papillomavirus (HPV) DNA testing has been promoted as primary screening strategy, the triage method has also evolved from morphological testing to a molecular biomarker detection to improve screening efficiency. In this study, we investigated the performance of three HPV inte...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-07-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523319300373 |
| _version_ | 1818296861295902720 |
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| author | Yunhui Jiang Chengyi Zhu Dan He Qinglei Gao Xun Tian Xin Ma Jun Wu Bhudev C. Das Konstantin Severinov Inga Isabel Hitzeroth Priya Ranjan Debata Rong Liu Liang Zou Long Shi Hua Xu Kaixiu Wang Yuxian Bao Leung Ross Ka-Kit Zeshan You Zifeng Cui Zheng Hu |
| author_facet | Yunhui Jiang Chengyi Zhu Dan He Qinglei Gao Xun Tian Xin Ma Jun Wu Bhudev C. Das Konstantin Severinov Inga Isabel Hitzeroth Priya Ranjan Debata Rong Liu Liang Zou Long Shi Hua Xu Kaixiu Wang Yuxian Bao Leung Ross Ka-Kit Zeshan You Zifeng Cui Zheng Hu |
| author_sort | Yunhui Jiang |
| collection | DOAJ |
| description | Background: Since human papillomavirus (HPV) DNA testing has been promoted as primary screening strategy, the triage method has also evolved from morphological testing to a molecular biomarker detection to improve screening efficiency. In this study, we investigated the performance of three HPV integration hot-spots, HMGA2, LRP1B, and TP63, as potential triage markers in HPV screening tests. Materials and Methods: This cross-sectional study was conducted from November 2016 to December 2017 in the First Affiliated Hospital of Sun Yat-sen University. Immunocytochemistry was carried out using residual cervical cell samples from 121 HPV-positive cases (23 normal, 24 cervical intraepithelial neoplasia (CIN) 1, and 74 CIN2+). Results: Of the 121 cases, 77 showed completely paired for the three biomarkers. In these 77 cases, receiver operating characteristic (ROC) analysis of HMGA2 showed the best potential for detecting CIN2+ among HPV+ cases (sensitivity 70%; specificity 91.89%; AUC 0.839). TP63 was second most effective biomarker (AUC 0.838; sensitivity 80%; specificity 81.08%). In contrast, LRP1B had the smallest AUC (0.801) among the three biomarkers but had the highest sensitivity (90%) and specificity (56.76%). To test the triage value of combining the three biomarkers, logistic regression was conducted followed by ROC comparison analysis. Promisingly, the combination of the three biomarkers gave the largest AUC of 0.951 with 92.5% sensitivity and 89.1% specificity (P < .0001 compared to liquid-based cytology test by Z-test). Conclusions: A combination of HMGA2, LRP1B, and TP63 as potential biomarkers may be useful for screening during triage of HPV-positive patients, particularly for detecting CIN2 + . |
| first_indexed | 2024-12-13T04:10:16Z |
| format | Article |
| id | doaj.art-02484634340e4a3aac4947981dab6463 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-13T04:10:16Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-02484634340e4a3aac4947981dab64632022-12-22T00:00:05ZengElsevierTranslational Oncology1936-52332019-07-01127959967Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive WomenYunhui Jiang0Chengyi Zhu1Dan He2Qinglei Gao3Xun Tian4Xin Ma5Jun Wu6Bhudev C. Das7Konstantin Severinov8Inga Isabel Hitzeroth9Priya Ranjan Debata10Rong Liu11Liang Zou12Long Shi13Hua Xu14Kaixiu Wang15Yuxian Bao16Leung Ross Ka-Kit17Zeshan You18Zifeng Cui19Zheng Hu20Department of Pathology, Jingmen No.2 People's Hospital/Institute for Cancer Prevention and Treatment，Jingchu University of Technology, Jingmen, Hubei Province, 448000, ChinaDepartment of Obstetrics & Gynecology, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442008, ChinaDepartment of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, ChinaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, ChinaCentral Hospital of Wuhan City, Huazhong University of Science and Technology, PR ChinaDepartment of Urology, The General Hospital of the People's Liberation Army, Beijing, ChinaSchool of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong Province, ChinaAmity Institute of Molecular Medicine & Stem Cell Research, Amity University Uttar Pradesh, Sector-125, Noida, IndiaSkolkovo Institute of Science and Technology, 100 Novaya str., Skolkovo, Moscow Region, RussiaE. Rybicki's Biopharming Research Unit. 11 Clifford Avenue, Vredehoek, 8001, Cape Town, South AfricaDepartment of Zoology, North Orissa University, Baripada, IndiaDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, ChinaJingmen No.2 People’s Hospital, Jingmen, Hubei Province, China.Jingmen No.2 People’s Hospital, Jingmen, Hubei Province, China.Jingmen No.2 People’s Hospital, Jingmen, Hubei Province, China.Jingmen No.2 People’s Hospital, Jingmen, Hubei Province, China.GeneRulor Company, Guangzhou, ChinaSchool of Public Health, The University of Hong Kong, Hong Kong, SAR, Dongguan Maternal and Child HospitalDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, ChinaDepartment of Obstetrics and Gynecology, Precision Medicine Institute, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, China; Address all correspondence to: Zheng Hu, or Zifeng Cui, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, China.Department of Obstetrics and Gynecology, Precision Medicine Institute, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, China; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, China; Address all correspondence to: Zheng Hu, or Zifeng Cui, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, China.Background: Since human papillomavirus (HPV) DNA testing has been promoted as primary screening strategy, the triage method has also evolved from morphological testing to a molecular biomarker detection to improve screening efficiency. In this study, we investigated the performance of three HPV integration hot-spots, HMGA2, LRP1B, and TP63, as potential triage markers in HPV screening tests. Materials and Methods: This cross-sectional study was conducted from November 2016 to December 2017 in the First Affiliated Hospital of Sun Yat-sen University. Immunocytochemistry was carried out using residual cervical cell samples from 121 HPV-positive cases (23 normal, 24 cervical intraepithelial neoplasia (CIN) 1, and 74 CIN2+). Results: Of the 121 cases, 77 showed completely paired for the three biomarkers. In these 77 cases, receiver operating characteristic (ROC) analysis of HMGA2 showed the best potential for detecting CIN2+ among HPV+ cases (sensitivity 70%; specificity 91.89%; AUC 0.839). TP63 was second most effective biomarker (AUC 0.838; sensitivity 80%; specificity 81.08%). In contrast, LRP1B had the smallest AUC (0.801) among the three biomarkers but had the highest sensitivity (90%) and specificity (56.76%). To test the triage value of combining the three biomarkers, logistic regression was conducted followed by ROC comparison analysis. Promisingly, the combination of the three biomarkers gave the largest AUC of 0.951 with 92.5% sensitivity and 89.1% specificity (P < .0001 compared to liquid-based cytology test by Z-test). Conclusions: A combination of HMGA2, LRP1B, and TP63 as potential biomarkers may be useful for screening during triage of HPV-positive patients, particularly for detecting CIN2 + .http://www.sciencedirect.com/science/article/pii/S1936523319300373 |
| spellingShingle | Yunhui Jiang Chengyi Zhu Dan He Qinglei Gao Xun Tian Xin Ma Jun Wu Bhudev C. Das Konstantin Severinov Inga Isabel Hitzeroth Priya Ranjan Debata Rong Liu Liang Zou Long Shi Hua Xu Kaixiu Wang Yuxian Bao Leung Ross Ka-Kit Zeshan You Zifeng Cui Zheng Hu Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women Translational Oncology |
| title | Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women |
| title_full | Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women |
| title_fullStr | Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women |
| title_full_unstemmed | Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women |
| title_short | Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women |
| title_sort | cytological immunostaining of hmga2 lrp1b and tp63 as potential biomarkers for triaging human papillomavirus positive women |
| url | http://www.sciencedirect.com/science/article/pii/S1936523319300373 |
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