Synthetic Biology Journal

   

Single-cell transcriptome combined with biosensing: a new framework for development of molecular diagnostic methods for cervical cancer

Yan ZHEN1,2, ZHAO Chao3, AN Jiahui1,2, XIE Wenjing1,2, PENG Hanyong1,2, ZHANG Xiaobo4, LI Mingzhu3, CHEN Xin1,2, XU Li1,2, XIE Qunhui1,2, WEI Lihui3   

  1. 1.State Key Laboratory of Environmental Chemistry and Toxicology，Research Center for Eco-Environmental Sciences，Chinese Academy of Sciences，Beijing，100085，China
    2.University of Chinese Academy of Sciences，College of Resources and Environment，Beijing，100049，China
    3.Department of Obstetrics and Gynecology，Peking University People’s Hospital，Beijing，100044，China
    4.Department of Pathology，Peking University People’s Hospital，Beijing，100044，China
  • Received:2025-08-04 Revised:2025-10-11 Published:2025-10-14
  • Contact: XIE Qunhui, WEI Lihui

单细胞转录组联合生物传感——宫颈癌分子诊断方法研发新框架

鄢震1,2, 赵超3, 安佳慧1,2, 谢文菁1,2, 彭汉勇1,2, 张晓波4, 李明珠3, 陈新1,2, 徐丽1,2, 谢群慧1,2, 魏丽惠3   

  1. 1.中国科学院生态环境研究中心，环境化学与环境毒理全国重点实验室，北京 100085
    2.中国科学院大学资源与环境学院，北京 100044
    3.北京大学人民医院妇产科，北京 100049
    4.北京大学人民医院病理科，北京 100049
  • 通讯作者: 谢群慧,魏丽惠
  • 作者简介:鄢震（1998—），男，硕士研究生。研究方向环境分子毒理学，网络毒理学。 E-mail：zhenyan_st@rcees.ac.cn
    赵超（1976—），女，北京大学人民医院妇科主任医师，研究方向为子宫颈癌前病变的筛查及诊断治疗，尤其是阴道镜检查、宫颈锥切手术治疗及妇科腹腔镜、宫腔镜手术治疗等。 E-mail：zhaochaocjr@163.com
    谢群慧（1976—），女，副研究员，硕士生导师，研究方向为持久性有机污染物的神经毒理机制、环境健康问题相关的生物标志物、基于分子毒理机制的毒性评估方法与技术等。 E-mail：qhxie@rcees.ac.cn
    魏丽惠（1944—），女，北京大学人民医院妇科主任医师，教授、博士生导师。研究方向为妇科疾病诊治及恶性肿瘤研究，擅长宫颈癌、子宫内膜癌、卵巢癌诊疗。 E-mail：weilhpku@163.com
  • 基金资助:
    科技部重点研发项目课题(E5L3030403);北京市通州区科学技术委员会项目(KJ2024CX060);中国科学院B 类先导专项项目(XDB0750300)

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Abstract:

Cervical cancer remains a significant global threat to women's health, responsible for approximately 600,000 new cases and 310,000 deaths worldwide in 2020. This highlights the urgent clinical need for more precise diagnosis and treatment. The current "three-step" screening strategy incorporates testing for high-risk human papillomavirus (HPV), one of the primary causative agents. However, this approach is hampered by a high false-positive rate, as HPV infection is not sufficient and necessary condition for the onset and progression of the cervical cancer; only a small proportion of infected women develop cervical intraepithelial neoplasia (CIN) or cancer. This often leads to overdiagnosis and overtreatment. Consequently, there is a pressing need, emphasized by recent WHO guidelines, to develop effective and functionally well-defined molecular biomarkers to improve the precision of clinical triage and diagnosis. This review addresses two critical bottlenecks impeding the discovery and translation of such biomarkers. The first is the insufficient resolution of existing technologies to overcome the challenge of tumor heterogeneity, where the molecular signals of critical malignant cell subpopulations are often obscured in bulk tissue analyses. The second bottleneck is the limitation of current detection methods used for validation, which often lack the sensitivity, quantitative reliability, and throughput required for robust clinical verification. To overcome these obstacles, we propose a research framework that integrates single-cell omics with advanced biosensing technologies. This framework first leverages single-cell transcriptomics to deconstruct tumor heterogeneity at an unparalleled resolution, enabling the discovery of higher-quality biomarker candidates by identifying gene expression signatures unique to the specific subgroup of cells driving malignant progression. Subsequently, these candidates are validated using biosensing systems engineered with synthetic biology principles, such as high-sensitivity in situ hybridization for quantitative tissue analysis and novel CRISPR-Cas-mediated nucleic acid detection technologies. These advanced platforms may offer programmable, ultra-sensitive, and highly specific detection of biomarkers in clinical samples. By synergizing high-resolution discovery with high-fidelity validation, this framework may not only facilitate a more complete characterization of novel biomarkers but also provide a direct pathway for translating these biosensing platforms into scalable clinical diagnostic kits. These technologies may serve as key drivers to enhance the early detection and precise management of cervical cancer.

Key words: cervical cancer, cancer molecular markers, biosensing, single-cell transcriptome

摘要：

宫颈癌（cervical cancer）作为全球性女性健康威胁之一，其精准诊疗是临床的迫切需求。现行的“三阶梯”宫颈癌筛查策略虽然已将宫颈癌的主要致病因素之一，高危型人乳头瘤病毒（human papillomavirus， HPV）感染，纳入其中，但因HPV感染并非宫颈癌患病的充分必要条件，筛查的假阳性率较高，容易导致过度诊疗，急需发展有效且功能明确的宫颈癌分子标志物（molecular markers），辅助临床诊疗，提高诊断的精准度。目前宫颈癌分子标志物的发现与转化过程中存在两个瓶颈问题，一是现有分子标志物研发技术手段对其功能解析的分辨率不足，难以克服肿瘤异质性的干扰。二是现有分子标志物检测方法在灵敏度和定量可靠性等方面的不足，导致了对其临床功能的验证和临床转化的限制。本文提出了一种联合单细胞转录组（single cell RNA sequencing， scRNA-seq）与生物传感（biosensing）技术的研究框架，以推动更高功能分辨率的宫颈癌分子标志物的发现，和面向临床应用的分子诊断方法的技术转化。该框架引入了目前先进单细胞转录组以及基于合成生物学原理设计的生物传感系统，如面向分子标志物的定量和组织分布研究的高灵敏的原位杂交技术和CRISPR-Cas介导的核酸检测新技术，这些技术作为关键的“转化引擎”，可为宫颈癌的早期发现和精准诊疗赋能。

关键词: 宫颈癌, 癌症分子标志物, 生物传感, 单细胞转录组

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