PTEN Expression Was Significantly Associated with PD-L1 Score but Not with EBV Infection in Gastric Cancer.
PTEN Expression Was Significantly Associated with PD-L1 Score but Not with EBV Infection in Gastric Cancer.
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DOI：
10.2147/ott.s374175
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发表时间：
2022
影响因子：
4
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中科院分区：
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胃癌（Gastric cancer，GC）是一种发病率和死亡率都很高的恶性肿瘤.基于分子特征的胃癌亚型鉴定有助于预后的预测和靶向治疗的选择。PTEN是一种特征性的肿瘤抑制因子，但其与不同GC亚型的关系尚不清楚。该队列包括248例确诊为胃癌并住院接受根治性胃切除术的患者。另外，从TCGA检索STAD的PTEN基因表达矩阵。采用qRT-PCR和免疫组化染色检测PTEN和PD-L1的mRNA和蛋白水平。采用多因素Logistic回归和Kaplan-Meier分析PTEN表达与临床特征的关系。在我们的研究中，PTEN在胃肿瘤中在mRNA和蛋白水平均下调。其失活与胃癌的组织学分级（P = 0.005）、神经浸润（P = 0.012）、浸润深度（P = 0.021）、淋巴结转移（P = 0.026）和TNM分期（P = 0.001）密切相关。PTEN高表达与PD-L1的TPS评分呈正相关（P = 0.010），与MSI和EBV感染无关。此外，TCGA数据验证了PTEN确实与组织学分级和浸润深度相关，并且与PD-L1表达正相关（R = 0.29，校正P < 0.001）。提示PTEN表达可作为胃癌发生、发展及免疫治疗方案选择的参考指标。
Gastric cancer (GC) remains a prevalent aggressive tumor with high morbidity and mortality globally. The identification of GC subtypes based on molecular features improved the prediction of prognosis and the selection of targeted therapies. PTEN is a characteristic tumor suppressor, while its association with different GC subtypes was unknown. The cohort consisted of 248 patients diagnosed with gastric cancer who were hospitalized and received radical gastrectomy. In addition, PTEN gene expression matrix of STAD was retrieved from TCGA. The mRNA and protein levels of PTEN and PD-L1 were detected using qRT-PCR and IHC staining. Multivariate logistic regression and Kaplan–Meier analysis were used to examine the relationship between PTEN expression and clinical characteristics. In our study, PTEN was downregulated in gastric tumors both in mRNA and protein levels. Its inactivation was closely linked to higher histological grade (P = 0.005), neural invasion (P = 0.012), depth of invasion (P = 0.021), lymph metastasis (P = 0.026), and TNM stage (P = 0.001) of GC in the present study. Moreover, according to the molecular subtypes, high PTEN expression was related to high TPS score of PD-L1 positively (P = 0.010) but was not associated with MSI and EBV infection. Further, TCGA data validated that PTEN was indeed correlated with histological grade and invasion depth and positively related to PD-L1 expression (R = 0.29, adjusted P < 0.001). The above results suggested that PTEN expression was a useful marker in gastric carcinogenesis and progression and in the selection of immunotherapy-based treatments for GC patients.