Table 2 Expression and clinical features of HLA-G in different tumors
From: Harnessing the potential of HLA-G in cancer therapy: advances, challenges, and prospects
Tumor | HLA-G expression, Method | Clinical implication | References |
|---|---|---|---|
Breast cancer | 94.1%, IHC | Positively associated with shorter OS and RFS | [244] |
Breast cancer | 70.7%, IHC | Positively associated with advanced disease stage | [107] |
Breast cancer | 66%, IHC | An independent prognosis factor | [51] |
Breast cancer | 62.2%, IHC | Positively associated with shorter survival | [111] |
Breast cancer | 41%, IHC | Positively associated with shorter DFS | [114] |
Breast cancer | 24%, IHC | Not associated with clinical outcome | [245] |
Breast cancer | Not mentioned | 14-bp Ins/Del and + 3142 C/G are associated with breast cancer susceptibility | [85] |
Breast cancer | Not mentioned | HLA-G 14bp Del and the + 3010/ + 3142/ + 3187 variants are more prevalent in breast cancer patients than in controls | [86] |
Breast cancer | Median sHLA-G plasma level 41.3 ng/ml, ELISA | A higher level of sHLA-G before NACT is related to disease progression | [142] |
Triple negative breast cancer (TNBC) | Median sHLA-G plasma level 8.6 ng/ml, ELISA | High post-chemotherapy sHLA-G levels were associated with the development of distant metastases and poorer disease outcomes. The combination of high sHLA-G levels post-chemotherapy and ILT-2 rs10416697C allele carrier status is a better independent indicator for disease outcome in TNBC than the lymph nodal status pre-chemotherapy | [144] |
Cervical cancer | 75.9%, IHC | An early marker for disease progression | [78] |
Cervical cancer | 45%, IHC | Association with the size of the main lesion, parametrial invasion, and lymph node metastasis | [137] |
Cervical cancer | 35.7% in CIN, 62.8% in SCC, IHC | Positively associated with disease progression | [80] |
Cervical cancer | 31.6%, IHC | Low expression of HLA-G5 is detected in all HPV-related cases | [94] |
Cervical cancer | Not mentioned | 14bp In/ + 3142G/ + 3142C allele is associated with susceptibility to HPV and the progression of cervical lesions | [69] |
Cervical cancer | Not mentioned |  + 3142 C/C genotype and C allele are associated with increased risk | [71] |
Cervical cancer | Not mentioned | 14 bp del allele promotes high-risk HPV infection, del/C haplotype is associated with invasive cervical cancer development | [72] |
Cervical cancer | Not mentioned | HLA-G*01:01:02 and HLA-G*01:03 alleles are related to persistent HPV16 infection | [75] |
Cervical cancer | Not mentioned | 14 bp In and + 3142G are increased in the HPV18-infected group compared with the control. HLA-G expression increases from CIN1 to CIN2/3 lesions and is highest in patients with adenocarcinoma | [77] |
Cervical cancer | 12.5% in CIN 1, 35.9% in CIN 2/3, 78% in cervical cancer, IHC | HLA-G expression increases from CIN 1 to CIN 2/3 and is highest in patients with cervical cancer. HLA-G expression is higher in CIN and cancer patients with HPV 16/18 than in CIN patients without HPV | [79] |
Cervical cancer | Median sHLA-G plasma level 115.8 U/ml, ELISA | sHLA-G level could be used as a diagnostic marker | [132] |
Cervical cancer | Median sHLA-G plasma level 50.86 U/ml, ELISA | sHLA-G level could be used as a diagnostic marker and decreases within 30Â days after radical hysterectomy | [145] |
Colorectal cancer | 70.7%, IHC | HLA-G expression above 55% was associated with a worse prognosis | [120] |
Colorectal cancer | 70.6%, IHC | Associated with the OS, an independent factor for OS | [139] |
Colorectal cancer | 64.6%, IHC | Associated with the depth of invasion, histological grade, host immune response, lymph nodal metastasis, and clinical stages of the disease | [124] |
Colorectal cancer | 59.1%, IHC | Associated with tumor node metastasis staging | [105] |
Colorectal cancer | Median sHLA-G plasma level 124.3 U/ml, ELISA | sHLA-G level is higher in colorectal cancer and may be a diagnostic marker | [246] |
Colorectal cancer | 14.9% in EpCAM+ cancer cells, Flow cytometry | Associated with lymph node metastasis and shorter OS | [102] |
Colorectal cancer | Not mentioned | HLA-G DelG haplotype is associated with increased cancer risk, while InsC haplotype is associated with decreased risk. InsC haplotype is independently associated with longer EFS | [84] |
Colorectal cancer | Median sHLA-G plasma level 59.17 U/ml, ELISA | sHLA-G level is correlated with HLA-G 3’UTR polymorphisms/haplotypes. Patients carrying + 3010G and + 3187G alleles have a higher chance of complete response to first-line FOLFIRI treatment | [131] |
Colorectal cancer | Median sHLA-G plasma level 36.8 U/ml, ELISA | sHLA-G above median levels (≥ 36.8 U/ml, sHLA-Ghigh) had a shorter survival time than those with sHLA-Glow (< 36.8 U/ml,), an independent prognostic factor | [108] |
Colorectal cancer | Median sHLA-G salivary level 18.84 U/ml, ELISA | sHLA-G salivary level is associated with advanced stages and sHLA-G serous level | [141] |
Colon cancer | 22.1%, IHC | Positively associated with shorter OS and DFS | [247] |
Esophageal cancer | 90%, IHC | Correlated with histologic grade, depth of invasion, nodal status, host immune response, clinical stage of disease, and worse prognosis, an independent prognostic factor | [248] |
Esophageal cancer | 70%, IHC; median sHLA-G plasma level 15.04 U/ml, ELISA | Associated with cancer cell differentiation, lymph node metastasis, and poor prognosis | [109] |
Esophageal cancer | 65.8%, IHC; median sHLA-G plasma level 152.4 U/ml, ELISA | Associated with advanced disease stage and poor survival, an independent prognostic factor | [126] |
Gastric cancer | 71%, IHC | Associated with the tumor location, histological grade, depth of invasion, lymph nodal metastasis, clinical stages of the disease, host immune response, and shorter OS, an independent prognostic factor | [249] |
Gastric cancer | 49.7%, IHC | Associated with the number of tumor-infiltrating Tregs, tumor invasion depth, invaded adjacent organs, clinical stages, and poorer prognosis (OS, DFS, and cancer-specific survival), an independent prognostic factor | [250] |
Gastric cancer | 30.8%, IHC | Positively associated with the number of tumor-infiltrating Tregs and negatively associated with the number of CD8 + T lymphocytes, an independent prognostic factor | [251] |
Gastric cancer | 25.5%, IHC | Positively associated with shorter OS | [117] |
Gastric cancer | Not mentioned | HLA-G 14bp Del allele and the 14bp Del/ + 3142 C variants are increased in patients with gastric cancer. The survival rate in patients bearing the 14bp DelL/Del genotype is lower than in patients with either Ins/Del or Ins/Ins genotypes | [87] |
Glioma | 60.2%, IHC | The absence of HLA-G expression is associated with a better long-term survival rate | [21] |
Liver cancer | 43% low expression, 57% high expression, IHC | Positively associated with Tregs/CD8 + ratio and shorter OS | [101] |
Liver cancer | 50.2%, IHC; median sHLA-G plasma level 92.49 U/ml, ELISA | Associated with advanced disease stage | [104] |
Liver cancer | median sHLA-G plasma level 178.8 U/ml, ELISA | Serum sHLA-G levels could be used as a diagnostic marker | [252] |
Liver cancer | Not mentioned | HLA-G 14bp I/D polymorphism is significantly correlated with tumor development in HBV/HCV( +) cases rather than in the HBV/HCV(-) subset | [82] |
Lung cancer | 75%, IHC | Associated with lymph nodal metastasis, clinical stages of the disease, host immune response, and shorter OS, an independent prognostic factor | [123] |
Lung cancer | 41.6%, IHC; median sHLA-G plasma level 34 U/ml, ELISA | HLA-G expression and plasma sHLA-G level are associated with disease stages and shorter survival | [99] |
Lung cancer | 34%, IHC; median sHLA-G plasma level 23.6 U/ml, ELISA | sHLA-G expression is higher in adenocarcinoma lesions than in squamous cell carcinoma and adenosquamous carcinoma lesions | [253] |
Lung cancer | 51.85%, IHC | Co-expression of ILT4/HLA-G is associated with regional lymph node involvement, advanced stages, and shorter OS | [121] |
Lung cancer | Median sHLA-G plasma level 53.3 U/ml, ELISA | Patients with the sHLA-G above median level (≥ 50 U/ml) have a significantly shorter survival time | [254] |
Oral squamous cell carcinoma | 50%, IHC | Positively associated with shorter OS | [255] |
Oral squamous cell carcinoma | 18.2% low expression, 81.8% high expression, IHC | Associated with clinical tumor stage and shorter OS | [118] |
Ovarian cancer | 72.4%, IHC | Associated with disease recurrence | [90] |
Ovarian cancer | 61%, IHC | sHLA-G level is higher in malignant as compared with benign ascites and could be used as a diagnostic marker | [91] |
Ovarian cancer | 79.7%, IHC | HLA-G5/-G6 expression was detected in 75.7% ovarian serous cancer, 63.6% mucinous cystadenocarcinoma and 100% endometrioid adenocarcinoma, 85.7% clear cell carcinoma, 100% sex cord-stromal tumor and 77.8% germ cell tumors | [92] |
Ovarian cancer | 35%, IHC | Associated with high-grade histology | [98] |
Ovarian cancer | 55% low expression, 20% median expression, 25% high expression | Associated with CA125 elevation and shorter OS | [113] |
Pancreatic cancer | 36.1% low expression, 63.9% high expression, IHC; median sHLA-G plasma levels 70.56 U/ml, ELISA | Associated with advanced stage, extra-pancreatic infiltration, lymph node involvement, and poor differentiation, an independent predictor for OS | [115] |
Pancreatic cancer | 39.2%, IHC | Positively associated with T stage and shorter OS | [256] |
Pancreatic cancer | 66%, IHC | Associated with advanced stages and grades | [106] |
Pancreatic cancer | 36.7%, IHC | Positively associated with shorter OS and DFS | [64] |
Thyroid cancer | 3% low expression, 17% median expression, 80% high expression in papillary thyroid carcinoma | In papillary thyroid carcinoma, the percentage of tumor cells exhibiting strong HLA-G staining is higher in patients with tumor size > 1.0 cm when compared to lesions < 1 cm | [103] |
Thyroid cancer | Median sHLA-G plasma level 24.84 ng/mL, ELISA | sHLA-G level is associated with tumor size, differentiation degree, capsule invasion, lymph node metastasis | [138] |
Papillary thyroid carcinoma | 44.3%, IHC | Associated with lymph node metastasis and capsular invasion | [257] |
Papillary thyroid carcinoma | Median sHLA-G plasma level 42.9 ng/mL, ELISA | sHLA-G level was higher in papillary thyroid carcinoma than that in healthy controls | [258] |