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Genetics and Genomics

The clinical implication and translational research of OSCC differentiation

British Journal of Cancer volume 130, pages 660–670 (2024)Cite this article

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Abstract

Background

The clinical value and molecular characteristics of tumor differentiation in oral squamous cell carcinoma (OSCC) remain unclear. There is a lack of a related molecular classification prediction system based on pathological images for precision medicine.

Methods

Integration of epidemiology, genomics, experiments, and deep learning to clarify the clinical value and molecular characteristics, and develop a novel OSCC molecular classification prediction system.

Results

Large-scale epidemiology data (n = 118,817) demonstrated OSCC differentiation was a significant prognosis indicator (p < 0.001), and well-differentiated OSCC was more chemo-resistant than poorly differentiated OSCC. These results were confirmed in the TCGA database and in vitro. Furthermore, we found chemo-resistant related pathways and cell cycle-related pathways were up-regulated in well- and poorly differentiated OSCC, respectively. Based on the characteristics of OSCC differentiation, a molecular grade of OSCC was obtained and combined with pathological images to establish a novel prediction system through deep learning, named ShuffleNetV2-based Molecular Grade of OSCC (SMGO). Importantly, our independent multi-center cohort of OSCC (n = 340) confirmed the high accuracy of SMGO.

Conclusions

OSCC differentiation was a significant indicator of prognosis and chemotherapy selection. Importantly, SMGO could be an indispensable reference for OSCC differentiation and assist the decision-making of chemotherapy.

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Fig. 1: Clinical characteristics of OSCC with different tumor differentiation in the SEER database.
Fig. 2: Molecular characteristics of OSCC with different tumor differentiation based on the TCGA database.
Fig. 3: The molecular characteristics and cytotoxicity study of OSCC with different differentiation in vitro.
Fig. 4: Molecular characteristics and clinical characteristics of the novel molecular classification (Molecular Grade, MG).
Fig. 5: The novel MG prediction system was established via deep learning and its external application in our independent multi-center (IMC) cohort.

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Data availability

The large-scale epidemiological information is available from the SEER database (https://seer.cancer.gov/) from 1975 to 2016 using SEER*Stat 8.3.6. The clinical information, somatic mutation profiles, RNA-seq profiles, and pathological images of the TCGA database were downloaded from https://portal.gdc.cancer.gov/. CNV profiles in the TCGA database were obtained from UCSC Xena (https://xenabrowser.net/). The RNA-seq profiles of OSCC cell lines were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/; GEO accession numbers: GSE98942 and GSE146483). The clinical information and pathological images of the IMC cohort are available within the article, its supplementary information, or from the corresponding first author upon reasonable request. Source data are provided in this study.

Code availability

The codes of this study are provided on GitHub (https://github.com/chxhstatis/SMGO).

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Acknowledgements

The authors thank all patients for their participation and donation of samples. Thanks for the support of the West China Hospital of Stomatology, Guangdong Provincial Stomatological Hospital, and the General Hospital of the People’s Liberation Army.

Funding

This work was supported by grants from: National Natural Science Foundation of China grant 82001059 (to HX). National Natural Science Foundation of China grant 82273165 (to XX). Sichuan Science and Technology Program grant 2022NSFSC1495 (to XX).

Author information

Authors and Affiliations

  1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, PR China

    Qianhui Shang, Yuchen Jiang, Jiakuan Peng, Ziang Xu, Weiqi Li, Dan Yang, Hang Zhao, Xiaoping Xu, Yu Zhou, Xin Zeng, Qianming Chen & Hao Xu

  2. Department of Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China

    Zixin Wan

  3. Key Laboratory of Oral Biomedical Research of Zhejiang Province, Affiliated Stomatology Hospital, Zhejiang University School of Stomatology, Hangzhou, Zhejiang, 310006, PR China

    Qianming Chen

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  1. Qianhui Shang
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Contributions

QS: contributed to acquisition, analysis, interpretation, drafted manuscript, and critically revised the manuscript. YJ: contributed to experiments, interpretation, and critically revised the manuscript. ZW: contributed to experiments and interpretation. JP: contributed to data acquisition, analysis and drafted the part of the manuscript. ZX: contributed to analysis and drafted the part of the manuscript. WL: contributed to interpretation. DY: contributed to acquisition. HZ: contributed to interpretation and critically revised the manuscript. XX: contributed to interpretation and critically revised the manuscript. YZ: contributed to interpretation and critically revised the manuscript. XZ: contributed to interpretation and critically revised the manuscript. QC: contributed to conception, design, acquisition, and critically revised the manuscript. HX: contributed to conception, design, acquisition, interpretation, and critically revised the manuscript. All authors gave final approval and agreed to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Qianming Chen or Hao Xu.

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The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the ethics committees of the West China Hospital of Stomatology, Guangdong Provincial Stomatological Hospital, and the General Hospital of the People’s Liberation Army [WCHSIRB-D-2014-004]. This study was conducted following the Declaration of Helsinki. All participants eligible for this study had completed a written informed consent form.

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Shang, Q., Jiang, Y., Wan, Z. et al. The clinical implication and translational research of OSCC differentiation. Br J Cancer 130, 660–670 (2024). https://doi.org/10.1038/s41416-023-02566-7

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