Li Shanshan, Liu Tingzhi, Liu Hailing, Zhai Xiaohui, Cao Taiyuan, Yu Hongen, Hong Wanjia, Lin Xiaoru, Li Ming, Huang Yan, Xiao Jian
Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Oncol. 2022 Aug 18;12:976762. doi: 10.3389/fonc.2022.976762. eCollection 2022.
One of the most common nasal external sites in extranodal Natural Killer/T-cell lymphoma (NKTCL) is in the gastrointestinal (GI) system. Despite this, reports on gastrointestinal-Natural Killer/T-cell lymphoma (GI-NKTCL) are very few. To obtain a better understanding of this manifestation of NKTCL, we conducted a retrospective study on GI-NKTCL to analyze its clinical features, genomic changes and immune infiltration.
We retrospectively collected patients diagnosed with GI-NKTCL in the Sixth Affiliated Hospital of Sun Yat-sen University from 2010 to 2020. From this cohort we obtained mutation data whole exome sequencing.
Genomic analysis from 15 patients with GI-NKTCL showed that the most common driving mutations were ARID1B(14%, 2/15), ERBB3(14%, 2/15), POT1(14%, 2/15), and TP53(14%, 2/15). In addition, we found the most common gene mutation in patients with GI-NKTCL to be RETSAT(29%, 4/15) and SNRNP70(21%, 3/15), and the most common hallmark pathway mutations to be G2M checkpoint pathway (10/15, 66.7%), E2F targets (8/15, 53.3%), estrogen response late (7/15, 46.7%), estrogen response early (7/15, 46.7%), apoptosis (7/15, 46.7%) and TNFA signaling NFKB (7/15, 46.7%). In the ICIs-Miao cohort, SNRNP7-wild-type (WT) melanoma patients had significantly prolonged overall survival (OS) time compared with SNRNP7 mutant type (MT) melanoma patients. In the TCGA-UCEC cohort, the patients with RETSAT-MT or SNRNP7-MT had significantly increased expression of immune checkpoint molecules and upregulation of inflammatory immune cells.
In this study, we explored GI-NKTCL by means of genomic analysis, and identified the most common mutant genes (RETSAT and SNRNP70), pathway mutations (G2M checkpoint and E2F targets) in GI-NKTCL patients. Also, we explored the association between the common mutant genes and immune infiltration. Our aim is that our exploration of these genomic changes will aid in the discovery of new biomarkers and therapeutic targets for those with GI-NKTCL, and finally provide a theoretical basis for improving the treatment and prognosis of patients with GI-NKTCL.
结外自然杀伤/ T细胞淋巴瘤（NKTCL）最常见的鼻外部位之一是胃肠道（GI）系统。尽管如此，关于胃肠道自然杀伤/ T细胞淋巴瘤（GI-NKTCL）的报道却非常少。为了更好地了解NKTCL的这种表现形式，我们对GI-NKTCL进行了一项回顾性研究，以分析其临床特征、基因组变化和免疫浸润情况。
我们回顾性收集了2010年至2020年在中山大学附属第六医院被诊断为GI-NKTCL的患者。从该队列中，我们通过全外显子测序获得了突变数据。
对15例GI-NKTCL患者的基因组分析表明，最常见的驱动突变是ARID1B（14%，2/15）、ERBB3（14%，2/15）、POT1（14%，2/15）和TP53（14%，2/15）。此外，我们发现GI-NKTCL患者中最常见的基因突变是RETSAT（29%，4/15）和SNRNP70（21%，3/15），最常见的标志性通路突变是G2M检查点通路（10/15，66.7%）、E2F靶点（8/15，53.3%）、雌激素反应晚期（7/15，46.7%）、雌激素反应早期（7/15，46.7%）、凋亡（7/15，46.7%）和TNFA信号-NFKB（7/15，46.7%）。在ICIs-Miao队列中，SNRNP7野生型（WT）黑色素瘤患者的总生存期（OS）明显长于SNRNP7突变型（MT）黑色素瘤患者。在TCGA-UCEC队列中，RETSAT-MT或SNRNP7-MT的患者免疫检查点分子表达明显增加，炎症免疫细胞上调。
在本研究中，我们通过基因组分析探索了GI-NKTCL，并确定了GI-NKTCL患者中最常见的突变基因（RETSAT和SNRNP70）、通路突变（G2M检查点和E2F靶点）。此外，我们还探索了常见突变基因与免疫浸润之间的关联。我们的目的是，对这些基因组变化的探索将有助于发现GI-NKTCL患者的新生物标志物和治疗靶点，并最终为改善GI-NKTCL患者的治疗和预后提供理论依据。
