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胃肝样腺癌的独特分子表型及免疫预后指数和肿瘤浸润淋巴细胞的潜在预后价值

Distinct molecular phenotype and the potential prognostic value of immune prognostic index and tumor infiltrating lymphocytes in hepatoid adenocarcinoma of stomach.

作者信息

Kang Muxing, Ma Xiaojing, Shi Jifei, Chen Guofeng, Jin Xiaoli, Wang Jun, Lin Lele, Wu Zhiwei, Chen Kaibo, Xu Jinghong, Huang Pintong, Chen Jian

机构信息

Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.

Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.

出版信息

Transl Oncol. 2022 May;19:101380. doi: 10.1016/j.tranon.2022.101380. Epub 2022 Mar 8.

Abstract

Hepatoid adenocarcinoma of the stomach (HAS) is a particular subtype of Gastric cancer (GC) with distinct pathological characteristics and genetic profile, but most HAS patients were received identical regimens as common GC. To date, only a few studies has been conducted to investigate the molecular characteristics of HAS, which may prevent the rational application of new anticancer strategies. To further obtain the genetic features and potential predictive and prognostic biomarkers of HAS, our current study evaluated the clinical implications of spectrum molecular markers in 36 surgical resection specimens. None Epstein-Barr virus (EBV) positive and/or micro-satellite instable high (MSI-h) tumors occurred in our study implies that the molecular classification of HAS should be mainly categorized into genomic stable (GS) and chromosomal instability (CIN) phenotypes, and wild type P53 status predicts better prognosis. More importantly, although the prognosis and clinical characteristics were independent of programmed cell death-ligand 1 (PD-L1), the presence of tumor infiltrating lymphocytes (TILs) still suggested that a portion of the enrolled HAS patients are potentially appropriate candidates for immune checkpoint blockade therapy. Additionally, the immune prognostic index (IPI) and derived neutrophil to lymphocyte ratio (dNLR) demonstrated their potential as reliable and economic indicators for predicting prognosis of HAS. We hope this first systematic evaluation will help in deciphering the molecular characterization and potential individualized regimens for this particular subtype of GC.

摘要

胃肝样腺癌(HAS)是胃癌(GC)的一种特殊亚型,具有独特的病理特征和基因谱,但大多数HAS患者接受的治疗方案与普通GC相同。迄今为止,仅开展了少数研究来调查HAS的分子特征,这可能会阻碍新型抗癌策略的合理应用。为了进一步获得HAS的基因特征以及潜在的预测和预后生物标志物,我们当前的研究评估了36例手术切除标本中谱分子标志物的临床意义。我们的研究中未出现爱泼斯坦-巴尔病毒(EBV)阳性和/或微卫星高度不稳定(MSI-h)肿瘤,这意味着HAS的分子分类应主要分为基因组稳定(GS)和染色体不稳定(CIN)表型,野生型P53状态预示着更好的预后。更重要的是,尽管预后和临床特征与程序性细胞死亡配体1(PD-L1)无关,但肿瘤浸润淋巴细胞(TILs)的存在仍表明,部分入组的HAS患者可能是免疫检查点阻断治疗的合适候选者。此外,免疫预后指数(IPI)和衍生的中性粒细胞与淋巴细胞比率(dNLR)显示出它们作为预测HAS预后的可靠且经济指标的潜力。我们希望这首次系统评估将有助于解读这种特殊亚型GC的分子特征和潜在的个体化治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c996/8908271/defd47a9703a/gr1.jpg

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