Prognostic and Clinicopathological Value of Human Leukocyte Antigen G in Gastrointestinal Cancers: A Meta-Analysis

Abstract

BackgroundThe prognostic value of human leukocyte antigen G (HLA-G) expression in gastrointestinal (GI) cancers remains controversial. Thus, this meta-analysis aimed to summarize available evidence from case-control or cohort studies that evaluated this association.MethodsThe PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched to identify relevant studies written in English published up to April 1, 2021, and with no initial date. Furthermore, the Google Scholar and Google databases were also searched manually for gray literature. The protocol for this meta-analysis was registered at PROSPERO (CRD42020213411). Pooled hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for end points using fixed- and random-effects statistical models to account for heterogeneity. Publication bias was evaluated using a funnel plot, Begg’s and Egger’s tests, and the “trim and fill” method.ResultsA total of 30 eligible articles with 5737 unique patients, including 12 studies on colorectal cancer (CRC), 6 on gastric cancer (GC), 5 on esophageal cancer (ESCC), 5 on hepatocellular carcinoma (HCC), and 2 on pancreatic adenocarcinoma (PC), were retrieved. Both univariate (HR = 2.01, 95% CI: 1.48 ~ 2.72) and multivariate (HR = 2.69, 95% CI: 2.03 ~ 3.55) analyses revealed that HLA-G expression was significantly correlated with poor overall survival (OS), regardless of the cancer type or antibody used. Subgroup analysis stratified by antibody showed that the 4H84 (I2 = 45.8%, P = 0.101) antibodies could be trustworthy and reliable for detecting HLA-G expression in GI cancers. In addition, HLA-G expression was found to be correlated with adverse clinicopathological parameters such as clinical stage, nodal status, metastasis, and histological grade but not tumor status.ConclusionElevated HLA-G expression indicates a poor prognosis for GI cancer patients, and screening for this marker could allow for the early diagnosis and treatment of GI cancers to improve survival rates.

Prognostic value of expression levels of miR‑148a, miR‑152 and HLA‑G in colon cancer

“…Numerous studies have demonstrated that high HLA-G expression was associated with poor prognosis in gastrointestinal cancer patients ( 28 – 32 ). However, there are few studies showing that there is no significant relationship between HLA-G expression and the prognosis of gastrointestinal cancers ( 33 – 35 ).…”

Meta-analysis of HLA-G 14bp insertion/deletion polymorphism and soluble HLA-G revealed an association with digestive cancers initiation and prognosis

“…These findings support the conclusion drawn from previous studies that tumour HLA-G expression is closely related to tumour progression and poor clinical outcomes in patients with cancer. A recent meta-analysis by Peng et al, performed on immunohistochemical and ELISA dosage [50], showed significant association of HLA-G with poor prognosis in gastric cancer. In addition, this meta-analysis showed that there was a significant correlation between HLA-G expression and TNM stage, lymph node status, and histological grade [50].…”

Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions

“…The non-classical MHC class I molecule HLA-G is under non-malignant conditions mainly expressed on extravillious trophoblasts [327,328], which invade maternal tissues during pregnancy, and promotes immune tolerance at the fetal-maternal interface [329][330][331]. Interestingly, many tumors, including colorectal, renal, breast, and lung tumors, have been shown to express HLA-G, which has often been associated with a worse outcome [201,[332][333][334][335][336]. In cancer, HLA-G expression can be involved in the evasion from anti-tumor immunity [337].…”