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The non-invasive diagnosis of colorectal cancer via a SOX9-based gene panel

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Abstract

Colorectal cancer (CRC) threatens human health seriously. Early diagnosis of CRC is critical to improving patient survival. Meanwhile, non-invasive detection through tumor-circulating markers can be an important auxiliary diagnosis. In this study, we performed targeted RNA sequencing in paired tumor and adjacent normal fresh frozen tissues from 68 patients, and we also measured circulating mRNA levels in 4 time-point plasma samples collected before and after operation or chemotherapy. Our results showed that SOX9 (6.73-fold with adjusted p value < 1 × 10–45), MYC (20.59-fold with adjusted p value < 1 × 10–57), and MMP7 (131.94-fold with adjusted p value < 1 × 10–78) highly expressed in tumor compared with adjacent normal tissues. Besides, the circulating mRNA of SOX9 (41.14-fold with adjusted p value < 1 × 10–13) in CRC was significantly higher than in the normal control as well. Moreover, a SOX9-based 9-gene panel (SOX9, GSK3A, FZD4, LEF1, DVL1, FZD7, NFATC1, KRT19, and RUVBL1) showed the non-invasive diagnostic value of CRC (AUC: 0.863 (0.766–0.960), TPR: 0.92, TNR: 0.87). In summary, SOX9 expression consistently increases in tumor and plasma samples from CRC patients, which indicates the important role of SOX9 in CRC progression and its potential in non-invasive diagnosis of CRC.

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Funding

This work was supported by Research Grants Council HK and HK Innovation and Technology Fund University-Industry Collaborative Programme (RGCQ71P and UIM/354), and National Natural Science Foundation of China (82103438).

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Author notes

  1. Vivian Weiwen Xue and Simon Siu Man Ng contributed equally to this work.

Authors and Affiliations

  1. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region, China

    Vivian Weiwen Xue, William Chi Shing Tai & Sze Chuen Cesar Wong

  2. Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, China

    Vivian Weiwen Xue

  3. Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Kowloon, Hong Kong Special Administrative Region, China

    Simon Siu Man Ng, Wing Wa Leung & Yee Ni Wong

  4. Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region, China

    Vivian Weiwen Xue, Hin Fung Tsang & Yin Kwan Evelyn Wong

  5. Department of Pathology, Kiang Wu Hospital, Santo António, Macau Special Administrative Region, China

    Heong Ting Wong

  6. Codex Genetics Limited, Kowloon, Hong Kong Special Administrative Region, China

    Allen Chi Shing Yu & Aldrin Kay Yuen Yim

  7. Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong Special Administrative Region, China

    William Chi Shing Cho

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  1. Vivian Weiwen Xue
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Contributions

SCCW contributed to the study conception and design. Material preparation, data collection, and analysis were performed by VWX and SCCW, and YKEW and HFT processed the patient samples and technical work before sequencing library preparation. SSMN, HTW, WWL, and YNW gave invaluable comments on the subject recruitment and data interpretation. ACSY and AKYY advised bioinformatic analysis. WCSC and WCST gave invaluable comments on data analysis. The first draft of the manuscript was written by VWX and SCCW, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sze Chuen Cesar Wong.

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Conflict of interest

The authors declare no competing interests.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Joint Chinese University of Hong Kong and New Territories Easter Cluster Clinical Research Ethics Committee (CREC Ref. No.: 2014.224).

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Informed consent was obtained from all individual participants included in the study.

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Xue, V.W., Ng, S.S.M., Tsang, H.F. et al. The non-invasive diagnosis of colorectal cancer via a SOX9-based gene panel. Clin Exp Med 23, 2421–2432 (2023). https://doi.org/10.1007/s10238-022-00970-6

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  • DOI: https://doi.org/10.1007/s10238-022-00970-6

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