Genomic characterization of peritoneal lavage cytology-positive gastric cancer.

IF 7 2区 医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2024-02-29 DOI:10.21147/j.issn.1000-9604.2024.01.07
Zhouqiao Wu, Tingfei Gu, Changxian Xiong, Jinyao Shi, Jingpu Wang, Ting Guo, Xiaofang Xing, Fei Pang, Ning He, Rulin Miao, Fei Shan, Yuan Zhou, Ziyu Li, Jiafu Ji
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Abstract

Objective: Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.

Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.

Results: Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0).

Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

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腹腔灌洗细胞学阳性胃癌的基因组特征。
目的腹腔淋巴结细胞学(CY1)阳性胃癌预后不良,腹膜转移风险高。然而,关于 CY1 的致病机制和特征尚缺乏证据,关于 CY1 的治疗也一直存在争议。因此,探索CY1的发病机制对于CY1胃癌的治疗策略和靶点至关重要:为了找出 CY1 胃癌的特异性驱动基因和标记基因,并最终为 CY1 的潜在标记和风险评估提供线索,本研究招募了 17 例细胞学阳性胃癌患者和 31 例匹配的细胞学阴性胃癌患者。入组标准基于腹腔镜诊断分期和脱落细胞的细胞学检查结果。然后对肿瘤样本进行全外显子组测序,以评估细胞学阳性胃癌的基因组特征:结果:最小绝对收缩和选择算子(LASSO)算法确定了43个细胞学阳性标记基因,而MutSigCV确定了42个细胞学阳性特异性驱动基因。CD3G和CDKL2既是CY1的驱动基因,也是标记基因。在突变特征、驱动基因突变和肿瘤亚克隆结构方面,CY1与腹腔淋巴结细胞学阴性(CY0)之间未发现明显差异:结论:CY1和CY0之间可能没有明显差异,CY1可能代表CY0胃癌的进展,而不是构成一个独立的亚型。因此,该基因组分析将提供有关 CY1 的关键分子信息,这可能会直接影响对 CY1 和 CY0 患者的治疗建议,并为基因组指导的临床试验和药物开发提供机会。
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来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
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