背景:小肠癌(SBC)是一种非常罕见的实体恶性肿瘤。因此,与其他胃肠道恶性肿瘤相比,我们关于SBC的知识,特别是它的分子属性,仍然有限。在这里,我们旨在概述中国SBC患者的基因特征,我们特别关注阐明区分SBC患者的遗传复杂性,这些患者的原发性肿瘤起源于小肠内不同的解剖区域。
方法:在2018年2月至2022年12月期间,从诊断为小肠癌的中国患者中连续收集了298例肿瘤样本。.进行下一代测序(NGS)以检测基因突变,评估微卫星不稳定性(MSI),并评估肿瘤突变负荷(TMB)。此外,,使用IHC来分析样品内的PD-L1表达水平。
结果:下一代测序(NGS)的结果揭示了在中国小肠癌(SBC)患者中观察到的主要基因突变。鉴定的前十大基因突变如下:TP53(53%),KRAS(51%),APC(31%),SMAD4(19%),VEGFA(15%),CDKN2A(15%),RAC1(15%),LRP1B(14%),管理(14%,CD74(13%)。随后的分析显示,本研究队列与纪念斯隆·凯特琳癌症中心(MSKCC)之间的基因景观存在差异,值得注意的是,在几个基因中鉴定出可区分的突变频率,包括ERBB2、FBXW7、PIK3CA、等。在该队列和MSKCC队列中均表现出对比。.此外,我们注意到SBC患者的基因突变频率存在差异,这取决于肿瘤起源于小肠的特定解剖部位.此外,具有高微卫星不稳定性(MSI-H)和肿瘤突变负荷(TMB)水平的患者的分布在起源于十二指肠的SBC患者中有所不同,空肠,和回肠.
结论:与其他人群相比,中国小肠癌患者表现出独特的遗传特征,突出独特的遗传景观。此外,在遗传景观中,观察到位于十二指肠的癌症患者与影响小肠其他区域的癌症患者之间存在明显差异,这表明这些患者应该接受不同的治疗。
Small bowel cancer (SBC) is a very rare solid malignancy. Consequently, compared with other malignant gastrointestinal tumors, our knowledge regarding SBC, specifically its molecular attributes, remains limited. Herein, we aim to provide an overview of the gene characteristics of Chinese patients with SBC, We particularly focus on elucidating the genetic intricacies that differentiate SBC patients whose primary tumors originate in distinct anatomical regions within the small bowel.
During the period ranging from February 2018 to December 2022, a total of 298 tumor samples were consecutively collected from Chinese patients diagnosed with small bowel cancer.. Next-generation sequencing (NGS) was performed to detect gene mutation, assess microsatellite instability (MSI), and evaluate tumor mutational burden (TMB). Additionally,, IHC was used to analyze the level of PD-L1 expression within the samples.
The outcomes of the next-generation sequencing (NGS) unveiled the predominant gene mutations observed in Chinese patients with small bowel cancer (SBC). The top ten gene mutations identified were as follows: TP53 (53%), KRAS (51%), APC (31%), SMAD4 (19%), VEGFA (15%), CDKN2A (15%), RAC1 (15%), LRP1B (14%), MGMT (14%, CD74 (13%). Subsequent analysis revealed disparities in the gene landscape between the cohort in this study and that of the Memorial Sloan Kettering Cancer Center (MSKCC), Notably, distinguishable mutational frequencies were identified in several genes, including ERBB2, FBXW7, PIK3CA, etc. which exhibited contrasting presence in both this cohort and the MSKCC cohort.. Furthermore, we noticed variations in the frequency of gene mutations among SBC patients depending on the specific anatomical site where the tumors originated within the small bowel. In addition, the distribution of patients with high microsatellite instability (MSI-H) and tumor mutational burden (TMB) levels varied among SBC patients with tumors originating from the duodenum, jejunum, and ileum.
Chinese patients with small bowel cancer exhibited a distinct genetic profile in comparison to other populations, highlighting a unique genetic landscape. Furthermore, noticeable disparities in the genetic landscape were observed between patients with cancer situated in the duodenum and those with cancer affecting other regions of the small bowel, this suggests that these patients should be treated differently.