tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2023-13-3s1-25-31tumors-1180Research ArticleСтатьиТранскриптомный RNA-SEQ анализ опухолевого микроокружения: на пути к разработке молекулярной классификации вирус-ассоциированного плоскоклеточного рака шейки маткиТранскриптомный RNA-SEQ анализ опухолевого микроокружения: на пути к разработке молекулярной классификации вирус-ассоциированного плоскоклеточного рака шейки маткиКурмышкинаО. В.КурмышкинаО. В.

Петрозаводск

Петрозаводск

КовчурП. И.КовчурП. И.

Петрозаводск

Петрозаводск

ВолковаТ. О.ВолковаТ. О.

Петрозаводск

Петрозаводск

VolkovaTO@yandex.ruФГБОУ ВО «Петрозаводский государственный университет (ПетрГУ)»РоссияФГБОУ ВО «Петрозаводский государственный университет (ПетрГУ)»Russian Federation202322112023133s12531Copyright © Курмышкина О.В., Ковчур П.И., Волкова Т.О., 20232023Курмышкина О.В., Ковчур П.И., Волкова Т.О.Курмышкина О.В., Ковчур П.И., Волкова Т.О.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/1180

Молекулярно-генетическое и иммунное разнообразие вирус-ассоциированного рака шейки матки представляет сравнительно малоисследованную проблему, в связи с чем вопрос о существовании разных молекулярных типов и возможности разработки молекулярной классификации пока остается открытым. Вклад иммунного и стромального компонентов опухолевого микроокружения в формирование специфического молекулярного фенотипа также не является в достаточной мере охарактеризованным, в особенности для наиболее ранних стадий прогрессии рака шейки матки. Анализ транскриптома как одной из составляющих молекулярного «портрета» опухоли с помощью технологий секвенирования нового поколения (Next Generation Sequencing, NGS) предоставляет основу для идентификации различных молекулярных типов с перспективой разработки классификации. Генетическое и фенотипическое, в том числе иммунологическое, разнообразие рака шейки матки позволит понять причины различий в агрессивности опухоли, прогнозе, эффективности терапии, а также расширить возможности применения иммунотерапии и комбинированных методов лечения. В данной статье приводится обзор международных и собственных исследований, проводимых в направлении обозначенных проблем.

Молекулярно-генетическое и иммунное разнообразие вирус-ассоциированного рака шейки матки представляет сравнительно малоисследованную проблему, в связи с чем вопрос о существовании разных молекулярных типов и возможности разработки молекулярной классификации пока остается открытым. Вклад иммунного и стромального компонентов опухолевого микроокружения в формирование специфического молекулярного фенотипа также не является в достаточной мере охарактеризованным, в особенности для наиболее ранних стадий прогрессии рака шейки матки. Анализ транскриптома как одной из составляющих молекулярного «портрета» опухоли с помощью технологий секвенирования нового поколения (Next Generation Sequencing, NGS) предоставляет основу для идентификации различных молекулярных типов с перспективой разработки классификации. Генетическое и фенотипическое, в том числе иммунологическое, разнообразие рака шейки матки позволит понять причины различий в агрессивности опухоли, прогнозе, эффективности терапии, а также расширить возможности применения иммунотерапии и комбинированных методов лечения. В данной статье приводится обзор международных и собственных исследований, проводимых в направлении обозначенных проблем.

транскриптомРНК-секвенированиерак шейки маткииммунное микроокружениеиммуносупрессияинтраэпителиальные неоплазиимолекулярный фенотиптранскриптомРНК-секвенированиерак шейки маткииммунное микроокружениеиммуносупрессияинтраэпителиальные неоплазиимолекулярный фенотипРабота выполнена при поддержке гранта РНФ № 21-15-00208Работа выполнена при поддержке гранта РНФ № 21-15-00208ReferencesArbyn M, Weiderpass E, Bruni L, de SanjoséS, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018 : a worldwide analysis. Lancet Glob Health (2020) 8 (2) : e191–203. doi: 10.1016/S2214-109X(19)30482-6.Arbyn M, Weiderpass E, Bruni L, de SanjoséS, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018 : a worldwide analysis. Lancet Glob Health (2020) 8 (2) : e191–203. doi: 10.1016/S2214-109X(19)30482-6.Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, et al. ; Cancer Genome Atlas Research Network ; et al. The Immune Landscape of Cancer. Immunity (2018) 48 (4) : 812–830. e14. doi: 10.1016/j.immuni.2018.03.023.Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, et al. ; Cancer Genome Atlas Research Network ; et al. The Immune Landscape of Cancer. Immunity (2018) 48 (4) : 812–830. e14. doi: 10.1016/j.immuni.2018.03.023.Bedognetti D, Cesano A, Marincola FM, Wang E. The Biology of Immune-Active Cancers and Their Regulatory Mechanisms. Cancer Treat Res (2020) 180 : 149–172. doi: 10.1007/978-3-030-38862-1_5.Bedognetti D, Cesano A, Marincola FM, Wang E. The Biology of Immune-Active Cancers and Their Regulatory Mechanisms. Cancer Treat Res (2020) 180 : 149–172. doi: 10.1007/978-3-030-38862-1_5.Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov (2019) 18 (3) : 197–218. doi: 10.1038/s41573-018-0007-y.Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov (2019) 18 (3) : 197–218. doi: 10.1038/s41573-018-0007-y.Zhao Z, Li J, Li H, Yuan Wu NY, Ou-Yang P, Liu S, et al. Integrative Bioinformatics Approaches to Screen Potential Prognostic Immune-Related Genes and Drugs in the Cervical Cancer Microenvironment. Front Genet (2020) 11 : 727. doi: 10.3389/fgene.2020.00727.Zhao Z, Li J, Li H, Yuan Wu NY, Ou-Yang P, Liu S, et al. Integrative Bioinformatics Approaches to Screen Potential Prognostic Immune-Related Genes and Drugs in the Cervical Cancer Microenvironment. Front Genet (2020) 11 : 727. doi: 10.3389/fgene.2020.00727.Xu F, Shen J, Xu S. Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment. Front Genet (2021) 12 : 663617. doi: 10.3389/fgene.2021.663617.Xu F, Shen J, Xu S. Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment. Front Genet (2021) 12 : 663617. doi: 10.3389/fgene.2021.663617.Jou J, Kato S, Miyashita H, Thangathurai K, Pabla S, DePietro P, et al. Cancer immunity marker RNA expression levels across gynecologic cancers : Implications for immunotherapy. Mol Cancer Ther (2023) Aug 25 : MCT-23–0270. doi: 10.1158/1535-7163.MCT-23-0270.Jou J, Kato S, Miyashita H, Thangathurai K, Pabla S, DePietro P, et al. Cancer immunity marker RNA expression levels across gynecologic cancers : Implications for immunotherapy. Mol Cancer Ther (2023) Aug 25 : MCT-23–0270. doi: 10.1158/1535-7163.MCT-23-0270.Zhou C, Tuong ZK, Frazer IH. Papillomavirus Immune Evasion Strategies Target the Infected Cell and the Local Immune System. Front Oncol (2019)9:682. doi: 10.3389/fonc.2019.00682.Zhou C, Tuong ZK, Frazer IH. Papillomavirus Immune Evasion Strategies Target the Infected Cell and the Local Immune System. Front Oncol (2019)9:682. doi: 10.3389/fonc.2019.00682.Jayshree RS. The Immune Microenvironment in Human Papilloma Virus-Induced Cervical Lesions-Evidence for Estrogen as an Immunomodulator. Front Cell Infect Microbiol (2021) 11 : 649815. doi: 10.3389/fcimb.2021.649815.Jayshree RS. The Immune Microenvironment in Human Papilloma Virus-Induced Cervical Lesions-Evidence for Estrogen as an Immunomodulator. Front Cell Infect Microbiol (2021) 11 : 649815. doi: 10.3389/fcimb.2021.649815.Budhwani M, Turrell G, Yu M, Frazer IH, Mehdi AM, Chandra J. Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients. Front Mol Biosci (2021) 8 : 622643. doi: 10.3389/fmolb.2021.622643.Budhwani M, Turrell G, Yu M, Frazer IH, Mehdi AM, Chandra J. Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients. Front Mol Biosci (2021) 8 : 622643. doi: 10.3389/fmolb.2021.622643.Frenel JS, Le Tourneau C, O’Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C, et al. Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer : Results From the Phase Ib KEYNOTE-028 Trial. J Clin Oncol (2017) 35 (36) : 4035–4041. doi: 10.1200/JCO.2017.74.5471.Frenel JS, Le Tourneau C, O’Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C, et al. Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer : Results From the Phase Ib KEYNOTE-028 Trial. J Clin Oncol (2017) 35 (36) : 4035–4041. doi: 10.1200/JCO.2017.74.5471.Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer : Results From the Phase II KEYNOTE-158 Study. J Clin Oncol (2019) 37 (17) : 1470–1478. doi: 10.1200/JCO.18.01265.Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer : Results From the Phase II KEYNOTE-158 Study. J Clin Oncol (2019) 37 (17) : 1470–1478. doi: 10.1200/JCO.18.01265.Hou J, Karin M, Sun B. Targeting cancer-promoting inflammation - have anti-inflammatory therapies come of age? Nat Rev Clin Oncol (2021) 18 (5) : 261–279. doi: 10.1038/s41571-020-00459-9.Hou J, Karin M, Sun B. Targeting cancer-promoting inflammation - have anti-inflammatory therapies come of age? Nat Rev Clin Oncol (2021) 18 (5) : 261–279. doi: 10.1038/s41571-020-00459-9.Fang L, Liu K, Liu C, Wang X, Ma W, Xu W, et al. Tumor accomplice : T cell exhaustion induced by chronic inflammation. Front Immunol (2022)13:979116. doi: 10.3389/fimmu.2022.979116.Fang L, Liu K, Liu C, Wang X, Ma W, Xu W, et al. Tumor accomplice : T cell exhaustion induced by chronic inflammation. Front Immunol (2022)13:979116. doi: 10.3389/fimmu.2022.979116.Bacolod MD, Barany F, Pilones K, Fisher PB, de Castro RJ. Pathways- and epigenetic-based assessment of relative immune infiltration in various types of solid tumors. Adv Cancer Re. (2019) 142 : 107–143. doi: 10.1016/bs.acr.2019.01.003.Bacolod MD, Barany F, Pilones K, Fisher PB, de Castro RJ. Pathways- and epigenetic-based assessment of relative immune infiltration in various types of solid tumors. Adv Cancer Re. (2019) 142 : 107–143. doi: 10.1016/bs.acr.2019.01.003.Rafael TS, Rotman J, Brouwer OR, van der Poel HG, Mom CH, Kenter GG, et al. Immunotherapeutic Approaches for the Treatment of HPV-Associated (Pre-) Cancer of the Cervix, Vulva and Penis. J Clin Med (2022) 11 (4) : 1101. doi: 10.3390/jcm11041101.Rafael TS, Rotman J, Brouwer OR, van der Poel HG, Mom CH, Kenter GG, et al. Immunotherapeutic Approaches for the Treatment of HPV-Associated (Pre-) Cancer of the Cervix, Vulva and Penis. J Clin Med (2022) 11 (4) : 1101. doi: 10.3390/jcm11041101.Livesey M, Rossouw SC, Blignaut R, Christoffels A, Bendou H. Transforming RNA-Seq gene expression to track cancer progression in the multi-stage early to advanced-stage cancer development. PLoS One (2023) 18 (4) : e0284458. doi: 10.1371/journal.pone.0284458.Livesey M, Rossouw SC, Blignaut R, Christoffels A, Bendou H. Transforming RNA-Seq gene expression to track cancer progression in the multi-stage early to advanced-stage cancer development. PLoS One (2023) 18 (4) : e0284458. doi: 10.1371/journal.pone.0284458.Gavish A, Tyler M, Greenwald AC, Hoefflin R, Simkin D, Tschernichovsky R, et al. Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours. Nature (2023) 618 (7965) : 598–606. doi: 10.1038/s41586-023-06130-4.Gavish A, Tyler M, Greenwald AC, Hoefflin R, Simkin D, Tschernichovsky R, et al. Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours. Nature (2023) 618 (7965) : 598–606. doi: 10.1038/s41586-023-06130-4.Zhang T, Zhuang L, Muaibati M, Wang D, Abasi A, Tong Q, et al. Identification of cervical cancer stem cells using single-cell transcriptomes of normal cervix, cervical premalignant lesions, and cervical cancer. EBioMedicine (2023) 92 : 104612. doi: 10.1016/j.ebiom.2023.104612.Zhang T, Zhuang L, Muaibati M, Wang D, Abasi A, Tong Q, et al. Identification of cervical cancer stem cells using single-cell transcriptomes of normal cervix, cervical premalignant lesions, and cervical cancer. EBioMedicine (2023) 92 : 104612. doi: 10.1016/j.ebiom.2023.104612.Li C, Hua K. Single-cell transcriptomics provides insights into the origin and immune microenvironment of cervical precancerous lesions. Cancer Commun (Lond) (2023) 43 (9) : 1055–1058. doi: 10.1002/cac2.12451.Li C, Hua K. Single-cell transcriptomics provides insights into the origin and immune microenvironment of cervical precancerous lesions. Cancer Commun (Lond) (2023) 43 (9) : 1055–1058. doi: 10.1002/cac2.12451.Kang J, Xiang X, Chen X, Jiang J, Zhang Y, Li L, Tang J. Angiogenesis-related gene signatures reveal the prognosis of cervical cancer based on single cell sequencing and co-expression network analysis. Front Cell Dev Biol (2023) 10 : 1086835. doi: 10.3389/fcell.2022.1086835.Kang J, Xiang X, Chen X, Jiang J, Zhang Y, Li L, Tang J. Angiogenesis-related gene signatures reveal the prognosis of cervical cancer based on single cell sequencing and co-expression network analysis. Front Cell Dev Biol (2023) 10 : 1086835. doi: 10.3389/fcell.2022.1086835.Ojesina AI, Lichtenstein L, Freeman SS, Pedamallu CS, Imaz-Rosshandler I, Pugh TJ, et al. Landscape of genomic alterations in cervical carcinomas. Nature (2014) 506 (7488) : 371–5. doi: 10.1038/nature12881.Ojesina AI, Lichtenstein L, Freeman SS, Pedamallu CS, Imaz-Rosshandler I, Pugh TJ, et al. Landscape of genomic alterations in cervical carcinomas. Nature (2014) 506 (7488) : 371–5. doi: 10.1038/nature12881.Cancer Genome Atlas Research Network ; Albert Einstein College of Medicine ; Analytical Biological Services ; Barretos Cancer Hospital ; Baylor College of Medicine ; Beckman Research Institute of City of Hope ; et al. Integrated genomic and molecular characterization of cervical cancer. Nature (2017) 543 (7645) : 378–384. doi: 10.1038/nature21386.Cancer Genome Atlas Research Network ; Albert Einstein College of Medicine ; Analytical Biological Services ; Barretos Cancer Hospital ; Baylor College of Medicine ; Beckman Research Institute of City of Hope ; et al. Integrated genomic and molecular characterization of cervical cancer. Nature (2017) 543 (7645) : 378–384. doi: 10.1038/nature21386.Chakravarthy A, Reddin I, Henderson S, Dong C, Kirkwood N, Jeyakumar M, et al. Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance. Nat Commun (2022) 13 (1) : 5818. doi: 10.1038/s41467-022-33544-x.Chakravarthy A, Reddin I, Henderson S, Dong C, Kirkwood N, Jeyakumar M, et al. Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance. Nat Commun (2022) 13 (1) : 5818. doi: 10.1038/s41467-022-33544-x.Litwin TR, Irvin SR, Chornock RL, Sahasrabuddhe VV, Stanley M, Wentzensen N. Infiltrating T-cell markers in cervical carcinogenesis : a systematic review and meta-analysis. Br J Cancer (2021) 124 (4) : 831–841. doi: 10.1038/s41416-020-01184-x.Litwin TR, Irvin SR, Chornock RL, Sahasrabuddhe VV, Stanley M, Wentzensen N. Infiltrating T-cell markers in cervical carcinogenesis : a systematic review and meta-analysis. Br J Cancer (2021) 124 (4) : 831–841. doi: 10.1038/s41416-020-01184-x.Lyu X, Li G, Qiao Q. Identification of an immune classification for cervical cancer and integrative analysis of multiomics data. J Transl Med (2021) 19 (1) : 200. doi: 10.1186/s12967-021-02845-y.Lyu X, Li G, Qiao Q. Identification of an immune classification for cervical cancer and integrative analysis of multiomics data. J Transl Med (2021) 19 (1) : 200. doi: 10.1186/s12967-021-02845-y.He C, Ren L, Yuan M, Liu M, Liu K, Qian X, Lu J. Identification of cervical squamous cell carcinoma feature genes and construction of a prognostic model based on immune-related features. BMC Women’s Health (2022) 22 (1) : 365. doi: 10.1186/s12905-022-01942-4.He C, Ren L, Yuan M, Liu M, Liu K, Qian X, Lu J. Identification of cervical squamous cell carcinoma feature genes and construction of a prognostic model based on immune-related features. BMC Women’s Health (2022) 22 (1) : 365. doi: 10.1186/s12905-022-01942-4.Li C, Wu H, Guo L, Liu D, Yang S, Li S, Hua K. Single-cell transcriptomics reveals cellular heterogeneity and molecular stratification of cervical cancer. Commun Biol (2022) 5 (1) : 1208. doi: 10.1038/s42003-022-04142-w.Li C, Wu H, Guo L, Liu D, Yang S, Li S, Hua K. Single-cell transcriptomics reveals cellular heterogeneity and molecular stratification of cervical cancer. Commun Biol (2022) 5 (1) : 1208. doi: 10.1038/s42003-022-04142-w.Lu X, Jiang L, Zhang L, Zhu Y, Hu W, Wang J, et al. Immune Signature-Based Subtypes of Cervical Squamous Cell Carcinoma Tightly Associated with Human Papillomavirus Type 16 Expression, Molecular Features, and Clinical Outcome. Neoplasia (2019) 21 (6) : 591–601. doi: 10.1016/j.neo.2019.04.003.Lu X, Jiang L, Zhang L, Zhu Y, Hu W, Wang J, et al. Immune Signature-Based Subtypes of Cervical Squamous Cell Carcinoma Tightly Associated with Human Papillomavirus Type 16 Expression, Molecular Features, and Clinical Outcome. Neoplasia (2019) 21 (6) : 591–601. doi: 10.1016/j.neo.2019.04.003.Li Y, Lu S, Wang S, Peng X, Lang J. Identification of immune subtypes of cervical squamous cell carcinoma predicting prognosis and immunotherapy responses. J Transl Med (2021) 19 (1) : 222. doi: 10.1186/s12967-021-02894-3.Li Y, Lu S, Wang S, Peng X, Lang J. Identification of immune subtypes of cervical squamous cell carcinoma predicting prognosis and immunotherapy responses. J Transl Med (2021) 19 (1) : 222. doi: 10.1186/s12967-021-02894-3.Lai W, Liao J, Li X, Liang P, He L, Huang K, Liang X, Wang Y. Characterization of the microenvironment in different immune-metabolism subtypes of cervical cancer with prognostic significance. Front Genet (2023) 14 : 1067666. doi: 10.3389/fgene.2023.1067666.Lai W, Liao J, Li X, Liang P, He L, Huang K, Liang X, Wang Y. Characterization of the microenvironment in different immune-metabolism subtypes of cervical cancer with prognostic significance. Front Genet (2023) 14 : 1067666. doi: 10.3389/fgene.2023.1067666.Øvestad IT, Engesæter B, Halle MK, Akbari S, Bicskei B, Lapin M, et al. High-Grade Cervical Intraepithelial Neoplasia (CIN) Associates with Increased Proliferation and Attenuated Immune Signaling. Int J Mol Sci (2021) 23 (1) : 373. doi: 10.3390/ijms23010373.Øvestad IT, Engesæter B, Halle MK, Akbari S, Bicskei B, Lapin M, et al. High-Grade Cervical Intraepithelial Neoplasia (CIN) Associates with Increased Proliferation and Attenuated Immune Signaling. Int J Mol Sci (2021) 23 (1) : 373. doi: 10.3390/ijms23010373.Halle MK, Munk AC, Engesæter B, Akbari S, Frafjord A, Hoivik EA, et al. A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival. Cancers (Basel) (2021) 13 (22) : 5737. doi: 10.3390/cancers13225737.Halle MK, Munk AC, Engesæter B, Akbari S, Frafjord A, Hoivik EA, et al. A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival. Cancers (Basel) (2021) 13 (22) : 5737. doi: 10.3390/cancers13225737.Jeon M, Xie Z, Evangelista JE, Wojciechowicz ML, Clarke DJB, Ma’ayan A. Transforming L1000 profiles to RNA-seq-like profiles with deep learning. BMC Bioinformatics (2022) 23 (1) : 374. doi: 10.1186/s12859-022-04895-5.Jeon M, Xie Z, Evangelista JE, Wojciechowicz ML, Clarke DJB, Ma’ayan A. Transforming L1000 profiles to RNA-seq-like profiles with deep learning. BMC Bioinformatics (2022) 23 (1) : 374. doi: 10.1186/s12859-022-04895-5.Wang Y, He M, Zhang G, Cao K, Yang M, Zhang H, Liu H. The immune landscape during the tumorigenesis of cervical cancer. Cancer Med (2021) 10 (7) : 2380–2395. doi: 10.1002/cam4.3833.Wang Y, He M, Zhang G, Cao K, Yang M, Zhang H, Liu H. The immune landscape during the tumorigenesis of cervical cancer. Cancer Med (2021) 10 (7) : 2380–2395. doi: 10.1002/cam4.3833.Li C, Hua K. Dissecting the Single-Cell Transcriptome Network of Immune Environment Underlying Cervical Premalignant Lesion, Cervical Cancer and Metastatic Lymph Nodes. Front Immunol (2022) 13 : 897366. doi: 10.3389/fimmu.2022.897366.Li C, Hua K. Dissecting the Single-Cell Transcriptome Network of Immune Environment Underlying Cervical Premalignant Lesion, Cervical Cancer and Metastatic Lymph Nodes. Front Immunol (2022) 13 : 897366. doi: 10.3389/fimmu.2022.897366.Kurmyshkina OV, Dobrynin PV, Kovchur PI, Volkova TO. Sequencing-based transcriptome analysis reveals diversification of immune response- and angiogenesis-related expression patterns of early-stage cervical carcinoma as compared with high-grade CIN. Front Immunol (2023) 14 : 1215607. doi: 10.3389/fimmu.2023.1215607.Kurmyshkina OV, Dobrynin PV, Kovchur PI, Volkova TO. Sequencing-based transcriptome analysis reveals diversification of immune response- and angiogenesis-related expression patterns of early-stage cervical carcinoma as compared with high-grade CIN. Front Immunol (2023) 14 : 1215607. doi: 10.3389/fimmu.2023.1215607.Wang X, Xu C, Sun H. DNA Damage Repair-Related Genes Signature for Immune Infiltration and Outcome in Cervical Cancer. Front Genet (2022) 13 : 733164. doi: 10.3389/fgene.2022.733164.Wang X, Xu C, Sun H. DNA Damage Repair-Related Genes Signature for Immune Infiltration and Outcome in Cervical Cancer. Front Genet (2022) 13 : 733164. doi: 10.3389/fgene.2022.733164.Wen H, Guo QH, Zhou XL, Wu XH, Li J. Genomic Profiling of Chinese Cervical Cancer Patients Reveals Prevalence of DNA Damage Repair Gene Alterations and Related Hypoxia Feature. Front Oncol (2022) 11 : 792003. doi: 10.3389/fonc.2021.792003.Wen H, Guo QH, Zhou XL, Wu XH, Li J. Genomic Profiling of Chinese Cervical Cancer Patients Reveals Prevalence of DNA Damage Repair Gene Alterations and Related Hypoxia Feature. Front Oncol (2022) 11 : 792003. doi: 10.3389/fonc.2021.792003.Liu C, Zhang M, Yan X, Ni Y, Gong Y, Wang C, et al. Single-cell dissection of cellular and molecular features underlying human cervical squamous cell carcinoma initiation and progression. Sci Adv (2023) 9 (4) : eadd8977. doi: 10.1126/sciadv.add8977.Liu C, Zhang M, Yan X, Ni Y, Gong Y, Wang C, et al. Single-cell dissection of cellular and molecular features underlying human cervical squamous cell carcinoma initiation and progression. Sci Adv (2023) 9 (4) : eadd8977. doi: 10.1126/sciadv.add8977.Zhou L, Qiu Q, Zhou Q, Li J, Yu M, Li K, et al. Long-read sequencing unveils high-resolution HPV integration and its oncogenic progression in cervical cancer. Nat Commun (2022) 13 (1) : 2563. doi: 10.1038/s41467-022-30190-1.Zhou L, Qiu Q, Zhou Q, Li J, Yu M, Li K, et al. Long-read sequencing unveils high-resolution HPV integration and its oncogenic progression in cervical cancer. Nat Commun (2022) 13 (1) : 2563. doi: 10.1038/s41467-022-30190-1.De Nola R, Loizzi V, Cicinelli E, Cormio G. Dynamic crosstalk within the tumor microenvironment of uterine cervical carcinoma : baseline network, iatrogenic alterations, and translational implications. Crit Rev Oncol Hematol (2021) 162 : 103343. doi: 10.1016/j.critrevonc.2021.103343.De Nola R, Loizzi V, Cicinelli E, Cormio G. Dynamic crosstalk within the tumor microenvironment of uterine cervical carcinoma : baseline network, iatrogenic alterations, and translational implications. Crit Rev Oncol Hematol (2021) 162 : 103343. doi: 10.1016/j.critrevonc.2021.103343.Kori M, Arga KY, Mardinoglu A, Turanli B. Repositioning of Anti-Inflammatory Drugs for the Treatment of Cervical Cancer Sub-Types. Front Pharmacol (2022) 13 : 884548. doi: 10.3389/fphar.2022.884548.Kori M, Arga KY, Mardinoglu A, Turanli B. Repositioning of Anti-Inflammatory Drugs for the Treatment of Cervical Cancer Sub-Types. Front Pharmacol (2022) 13 : 884548. doi: 10.3389/fphar.2022.884548.

The authors declare that there are no conflicts of interest present.