Liya Zhang1, Yi Jiang2, Xiaofan Lu1, Huiling Zhao1, Chen Chen1, Yaoyan Wang1, Wenjun Hu1, Yue Zhu1, Hangyu Yan1, Fangrong Yan3. 1. Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, PR China. 2. Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. 3. Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, PR China. Electronic address: f.r.yan@163.com.
Abstract
OBJECTIVE: It is uncommon for cervical cancer patients to be diagnosed without a human papillomavirus (HPV) infection. As prophylactic vaccines against high-risk HPV types are an ineffective preventive measure for these patients it is essential to identify differential biomarkers that may be associated with detection, prognosis and novel targeted therapies. The objective of this study was to compare the two entities, HPV+ and HPV- cervical cancers, based on TCGA public data. METHODS: We collected and analyzed clinical information of 299 cervical cancer patients as the first step, then identified differential expressed genes and conducted downstream analyses to characterize this tumor based on HPV status, including functional annotation, pathway mapping, survival analysis and comparative somatic mutation landscapes. We further inferred the likelihood of responding to traditional treatment including radiotherapy and chemotherapy. RESULTS: It was found that HPV- tumors were likely to occur at an older age and were often adenocarcinomas or adenosquamous carcinomas, and there was no significant overall survival difference between HPV+ vs. HPV- tumors. Gene expression profiles of HPV+ and HPV- tumors differed especially in ANKRD7, SERPINB3, EMX2, MEI1, RNF212, RP11-13 K12.5, RP11-325F22.2 and ZFR2 which were significantly relevant to cervical cancer prognosis. TP53, ARID5B, ARID1A, CTNNB1 and PTEN were significantly differentially mutated between HPV+ and HPV- tumors. Results of radiotherapy analyses demonstrated that CDO1, PCDHB2 and MYOD1 were different between the two subsets. In addition, RP11-299 L17.3, SLC14A2, FGF18 and OASL represented different drug-sensitivity to cisplatin between both. CONCLUSIONS: These potential biomarkers may offer insights to further personalize therapeutic decision-making to improve survival in HPV- cervical cancer patients.
OBJECTIVE: It is uncommon for cervical cancerpatients to be diagnosed without a human papillomavirus (HPV) infection. As prophylactic vaccines against high-risk HPV types are an ineffective preventive measure for these patients it is essential to identify differential biomarkers that may be associated with detection, prognosis and novel targeted therapies. The objective of this study was to compare the two entities, HPV+ and HPV- cervical cancers, based on TCGA public data. METHODS: We collected and analyzed clinical information of 299 cervical cancerpatients as the first step, then identified differential expressed genes and conducted downstream analyses to characterize this tumor based on HPV status, including functional annotation, pathway mapping, survival analysis and comparative somatic mutation landscapes. We further inferred the likelihood of responding to traditional treatment including radiotherapy and chemotherapy. RESULTS: It was found that HPV- tumors were likely to occur at an older age and were often adenocarcinomas or adenosquamous carcinomas, and there was no significant overall survival difference between HPV+ vs. HPV- tumors. Gene expression profiles of HPV+ and HPV- tumors differed especially in ANKRD7, SERPINB3, EMX2, MEI1, RNF212, RP11-13 K12.5, RP11-325F22.2 and ZFR2 which were significantly relevant to cervical cancer prognosis. TP53, ARID5B, ARID1A, CTNNB1 and PTEN were significantly differentially mutated between HPV+ and HPV- tumors. Results of radiotherapy analyses demonstrated that CDO1, PCDHB2 and MYOD1 were different between the two subsets. In addition, RP11-299 L17.3, SLC14A2, FGF18 and OASL represented different drug-sensitivity to cisplatin between both. CONCLUSIONS: These potential biomarkers may offer insights to further personalize therapeutic decision-making to improve survival in HPV- cervical cancerpatients.
Authors: Alexandra McMellen; Elizabeth R Woodruff; Bradley R Corr; Benjamin G Bitler; Marisa R Moroney Journal: Int J Mol Sci Date: 2020-06-16 Impact factor: 5.923
Authors: Xinyi Liu; Ping Liu; Rebecca D Chernock; Krystle A Lang Kuhs; James S Lewis; Jingqin Luo; Hiram A Gay; Wade L Thorstad; Xiaowei Wang Journal: EBioMedicine Date: 2020-10-07 Impact factor: 8.143