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北京大学学报（医学版） ›› 2023, Vol. 55 ›› Issue (4): 697-701. doi: 10.19723/j.issn.1671-167X.2023.04.021

• 论著 • 上一篇    下一篇

全外显子测序及相关指标在口腔鳞状细胞癌精准治疗中的应用价值

谢尚,蔡志刚,单小峰*()   

  1. 北京大学口腔医学院·口腔医院口腔颌面外科，国家口腔医学中心，国家口腔疾病临床医学研究中心，口腔生物材料和数字诊疗装备国家工程研究中心，北京 100081
  • 收稿日期:2022-10-10 出版日期:2023-08-18 发布日期:2023-08-03
  • 通讯作者: 单小峰 E-mail:kqsxf@263.net
  • 基金资助:
    国家重点研发计划(2022YFC2504200);国家自然科学基金(82002878);北京大学口腔医院临床新技术新疗法项目(PKUSSNCT-22A14)

Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma

Shang XIE,Zhi-gang CAI,Xiao-feng SHAN*()   

  1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
  • Received:2022-10-10 Online:2023-08-18 Published:2023-08-03
  • Contact: Xiao-feng SHAN E-mail:kqsxf@263.net
  • Supported by:
    the National Key Research and Development Program of China(2022YFC2504200);the National Natural Science Foundation of China(82002878);the Program for New Clinical Techniques and Therapies of Peking University Hospital of Stomatology(PKUSSNCT-22A14)

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摘要：

目的: 探索全外显子测序及相关指标在口腔鳞状细胞癌(oral squamous cell carcinoma，OSCC)个性化精准治疗中的意义和推广应用的可行性。方法: 选取2021年1月至2022年6月在北京大学口腔医院行OSCC根治手术并接受基因检测和免疫相关指标检测的患者，结合其临床病理特点，筛选潜在的靶向药物和免疫药物，以评估基因检测使患者受益的可能性。主要评估指标包括基因突变数量、联合阳性分数(combined positive score，CPS)、肿瘤突变负荷(tumor mutation burden，TMB)、微卫星序列状态和人类白细胞抗原B位点(human leukocyte antigen B，HLA-B)等。采用Excel进行统计学分析。结果: 共10例患者，排除1例腺样囊性癌，9例OSCC患者纳入本研究，其中男性6例，女性3例，平均年龄(55.44±9.59)岁。肿瘤位置：颊部5例，舌部3例，牙龈1例。基因检测结果发现，3例(33.3%)患者肿瘤组织内未发现基因突变，5例(55.6%)存在唯一的TP53基因突变，1例(11.1%)存在TP53和CHEK1突变，但暂无上市药物可用于这些突变基因的靶向治疗。遗传性肿瘤基因检测结果发现，所有患者中均未发现遗传肿瘤基因存在，提示OSCC为遗传性肿瘤的可能性较低。在免疫疗效相关标志物检测方面，CPS检测结果发现8例患者CPS≥1；TMB检测结果发现，TMB中位数为0.72 mutations/Mb(0~4.32 mutations/Mb)，均较低；微卫星序列状态检测结果发现阴性及阳性对照结果均正确，提示所检测肿瘤组织均为微卫星稳定性；HLA-B检测结果发现仅有1例患者存在B62基因突变，提示OSCC组织标本中HLA-B的B44和B62相关基因型非常低。结论: 现有结果不支持基因检测和免疫相关指标检测在OSCC治疗中的广泛应用及推广。

关键词: 癌，鳞状细胞, 口腔肿瘤, 全外显子组测序, 基因检测, 精准医学

Abstract:

Objective: To explore the significance and feasibility of whole exon sequencing and immune related indexes in personalized precision treatment of oral squamous cell carcinoma (OSCC). Methods: We retrospectively screened the patients who underwent surgery for oral cancer in Peking University Hospital of Stomatology and underwent genetic and immune biomarkers tests between January 2021 and June 2022. Combined with the clinicopathological characteristics of patients, potential targeted drugs and immunotherapy drugs were screened to evaluate the possibility of gene testing benefiting OSCC. The main evaluation indicators included the number of gene mutations, combined positive score (CPS), tumor mutation burden (TMB), microsatellite sequence status and human leukocyte antigen B (HLA-B) locus. Excel was used for statistical analysis. Results: A total of 10 patients were enrolled and 9 were included in this study, including 6 males and 3 females, with an average age of (55.44±9.59) years. The tumor location was buccal (5 cases), tongue (3 cases) and gingival (1 case). The results of genetic testing showed that 3 (33.3%) patients had no gene mutations in the tumor tissue, 5 (55.6%) patients had unique TP53 gene mutations, and 1 (11.1%) patient had TP53 and CHEK1 mutations. However, no drugs were available for targeted therapy of the mutated genes. The genetic tumor gene testing results showed that no genetic tumor gene was found in all the patients, suggesting that OSCC had a low possibi-lity of hereditary tumor. In terms of immune efficacy related markers, CPS test results showed that 8 patients had CPS≥1. TMB detection results showed that the median value of TMB value was 0.72 mutations/Mb, and the range was 0 to 4.32 mutations/Mb. The negative and positive control results of microsatellite sequence status were consistent, indicating that all the tumor tissues detected were microsatellite stability. The results of HLA-B detection showed that only one patient had B62 gene mutation, suggesting that the B44 and B62 related genotypes of HLA-B in OSCC tissue samples were low. Conclusion: The present results do not support the wide application and promotion of genetic testing and immune related indexes in OSCC.

Key words: Carcinoma, squamous cell, Mouth neoplasms, Whole exome sequencing, Genetic testing, Precision medicine

中图分类号: 

  • R739.8

表1

纳入研究的9例患者的临床病理特点"

PatientAge/yearsGenderTumor subsitesT stageN stageM stageDepth of invasion/cmPrecancerous lesions
143MaleTongueT2100.7Oral lichen planus
253FemaleBuccalT2001.0No
361FemaleBuccalT3203.0No
449MaleTongueT2000.2No
573FemaleBuccalT2000.8No
659MaleGingivalT3002.0No
743MaleTongueT1000.3No
858MaleBuccalT3102.0No
960MaleBuccalT3202.0No

表2

免疫抑制剂相关指标检测结果"

PatientCPSTMB/(mutations/Mb)Microsatellite sequence statusDetection HLA-B mutation site (B44 or B62 related genotypes)
141.44MSSNone
2800.72MSSNone
3421.44MSSNone
4903.6MSSNone
5300.69MSSNone
610.49MSSNone
7< 10MSSNone
8354.32MSSNone
9600MSSB62-related genotypes
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ISSN 1671-167X
CN 11-4691/R
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