Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Cancer Res Ther. 2020 Dec;16(Supplement):S165-S171. doi: 10.4103/jcrt.JCRT_429_18.
In the present study, we evaluated the clinical prognostic value of human leukocyte antigen (HLA (Class I tumor cell expression in a series of colorectal cancer (CRC) patients and also explored the association of this expression profile with molecular features such as mutation status of KRAS and BRAF, microsatellite stability status, and clinicopathological characteristics of the patients.
Formalin-fixed paraffin-embedded tumor tissue of 258 CRC patient's sections were immunohistochemically stained and subsequently quantified for HLA Class I expression by the tumor cells. Determination of microsatellite instability (MSI) tumor status was ascertained using mononucleotide repeat microsatellite targets. KRAS and BRAF mutations were screened by polymerase chain reaction (PCR)-sequencing and cast-PCR, respectively.
HLA Class I expression was normal in 91 cases (35.3%), downregulated in 119 (46.1%), and loss of expression in 48 (18.6%) cases. Forty (15.5%) tumors were MSI-H (MSH), 49 were MSI-L (19%), and 169 were microsatellite stable (MSS) (65.5%). Thirty-six (14%) and 15 (5.8%) of the patients exhibited mutation in the KRAS and BRAF, respectively. It was found that patients with downregulated expression of HLA Class I were associated with Stage II tumors (P < 0.001) and a MSS tumor status (P < 0.001), while patients with loss of expression were associated with MSH status (P < 0.001). Univariate and multivariate analyses revealed that HLA Class I downregulated expression was an independent prognostic parameter for shorter overall patient survival time (hazard ratio: 1.8, P = 0.003).
HLA Class I expression is an independent and sensitive clinical prognostic marker that might be used in CRC patients.
本研究评估了人类白细胞抗原（HLA）（I 类肿瘤细胞表达在一系列结直肠癌（CRC）患者中的临床预后价值，并探讨了这种表达谱与分子特征（如 KRAS 和 BRAF 突变状态、微卫星不稳定性状态和患者的临床病理特征）的关联。
免疫组织化学染色 258 例 CRC 患者组织的福尔马林固定石蜡包埋肿瘤组织，并用肿瘤细胞对 HLA 类 I 表达进行定量。通过单核苷酸重复微卫星靶标确定微卫星不稳定性（MSI）肿瘤状态。使用聚合酶链反应（PCR）-测序和 CAST-PCR 分别筛选 KRAS 和 BRAF 突变。
HLA 类 I 表达正常 91 例（35.3%），下调 119 例（46.1%），失表达 48 例（18.6%）。40 例（15.5%）肿瘤为 MSI-H（MSH），49 例为 MSI-L（19%），169 例为微卫星稳定（MSS）（65.5%）。36 例（14%）和 15 例（5.8%）患者的 KRAS 和 BRAF 发生突变。发现 HLA 类 I 下调表达的患者与 II 期肿瘤（P < 0.001）和 MSS 肿瘤状态（P < 0.001）相关，而失表达的患者与 MSH 状态相关（P < 0.001）。单因素和多因素分析表明，HLA 类 I 下调表达是总患者生存时间较短的独立预后参数（风险比：1.8，P = 0.003）。
HLA 类 I 表达是独立和敏感的临床预后标志物，可用于 CRC 患者。
