Association of HLA-G 3′UTR polymorphisms and haplotypes with colorectal cancer susceptibility and prognosis

Dhouioui, Sabrine; Laaribi, Ahmed-Baligh; Boujelbène, Nadia; Jelassi, Refka; Salah, Hamza Ben; Bellali, Hedia; Ouzari, Hadda‐Imene; Mézlini, Amel; Zemni, Inès; Chelbi, Hanène; Zidi, Inès

doi:10.1016/j.humimm.2021.10.003

Cited by 7 publications

(4 citation statements)

References 47 publications

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“…Other works and meta-analysis described an association of HLA-G 3'UTR haplotypes to the development and severity of different malignancies, such as breast and colorectal cancer, were 14bp Del/Del and + 3142 C/C, both forming UTR-1 and UTR6 haplotypes, showed association to risk of developing both cancers (20,21). Moreover, other authors showed an association of HLA-G levels of expression and the 14bp polymorphism in gynecologic cancers (22), and, in the same vein of thinking, loss of miR-152 increases HLA-G expression in vitro (23), mimicking the effect of + 3142 polymorphisms, as miR-152 is not able to bind + 3142 C/C.…”

Section: Discussionmentioning

confidence: 98%

HLA-G High-expressor 3’UTR Markers Are Linked to Gastric Cancer Development and Survival

Vaquero-Yuste,

Juarez,

Molina-Alejandre

et al. 2024

Preprint

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Gastric cancer ranks fifth in both world prevalence and lethality, with a 5-year survival of less than 30%. HLA-G, a non-classical class I HLA gene, has emerged as a potential marker for cancer susceptibility and prognosis due to its immunomodulatory properties. Its level of expression is regulated by polymorphisms in the 3’ untranslated region (3’UTR) polymorphisms, which form various combined haplotypes (UTR-1 to -9). In this study, we examined HLA-G 3’UTR polymorphisms in paired tissue samples from 111 patients with gastric adenocarcinoma and 119 healthy controls. Polymorphism analysis was performed using PCR and Sanger sequencing, followed by statistical analysis using SNPStats software. Survival analysis was conducted using Kaplan-Meier curves and multivariate Cox regression models. High-expressor HLA-G 3’UTR haplotypes (UTR-1 and UTR-6) were significantly associated with gastric cancer susceptibility, indicating a potential role in tumor immune evasion. Additionally, the 14 base pair insertion/deletion polymorphism (14bp I/D) emerged as a prognostic marker, with D/D genotype carriers showing lower survival rates compared to I/D and I/I genotype carriers. Our study highlights the clinical relevance of HLA-G polymorphisms in gastric cancer, suggesting their potential as prognostic markers and therapeutic targets. Further elucidation of HLA-G-related pathways could lead to personalized treatment strategies and improved patient outcomes in gastric cancer.

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Section: Discussionmentioning

confidence: 98%

HLA-G High-expressor 3’UTR Markers Are Linked to Gastric Cancer Development and Survival

Vaquero-Yuste,

Juarez,

Molina-Alejandre

et al. 2024

Preprint

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“…In various cancer types, there is significant aberrant induction of HLA-G expression. This abnormal expression is strongly correlates with tumor metastasis and poor prognosis (112,113). HLA-G functions as both an immune tolerance and tumor-promoting factor (114).…”

Section: Human Leukocyte Antigen G and Ementioning

confidence: 99%

“…Extensive studies have established HLA-G as a distinct immune checkpoint. Its immunotolerance functions include suppressing LT CD8+ and NK cells' cytolytic effects, inhibiting LT CD4+ and dendritic cells' maturation (20), and enhancing Th2 cytokines (113). In CRC, undifferentiated cells release HLA-G at the invasion front.…”

Section: Human Leukocyte Antigen G and Ementioning

confidence: 99%

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

Gan,

Li,

et al. 2024

Front. Immunol.

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Worldwide, gastrointestinal (GI) cancer is recognized as one of the leading malignancies diagnosed in both genders, with mortality largely attributed to metastatic dissemination. It has been identified that in GI cancer, a variety of signaling pathways and key molecules are modified, leading to the emergence of an immunotolerance phenotype. Such modifications are pivotal in the malignancy’s evasion of immune detection. Thus, a thorough analysis of the pathways and molecules contributing to GI cancer’s immunotolerance is vital for advancing our comprehension and propelling the creation of efficacious pharmacological treatments. In response to this necessity, our review illuminates a selection of groundbreaking cellular signaling pathways associated with immunotolerance in GI cancer, including the Phosphoinositide 3-kinases/Akt, Janus kinase/Signal Transducer and Activator of Transcription 3, Nuclear Factor kappa-light-chain-enhancer of activated B cells, Transforming Growth Factor-beta/Smad, Notch, Programmed Death-1/Programmed Death-Ligand 1, and Wingless and INT-1/beta-catenin-Interleukin 10. Additionally, we examine an array of pertinent molecules like Indoleamine-pyrrole 2,3-dioxygenase, Human Leukocyte Antigen G/E, Glycoprotein A Repetitions Predominant, Clever-1, Interferon regulatory factor 8/Osteopontin, T-cell immunoglobulin and mucin-domain containing-3, Carcinoembryonic antigen-related cell adhesion molecule 1, Cell division control protein 42 homolog, and caspases-1 and -12.

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“…Additional 5 articles were omitted due to lack or irrelevant data. Therefore, in total, 9 articles met our inclusion criteria [23,24,25,26,27,28,29,30,31] (Table 1, Figure 1).…”

Section: Studies Included In the Meta-analysismentioning

confidence: 99%

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

Dhouioui

Boujelbène²,

Ouzari³

et al. 2022

Heliyon

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Association of HLA-G 3′UTR polymorphisms and haplotypes with colorectal cancer susceptibility and prognosis

Cited by 7 publications

References 47 publications

HLA-G High-expressor 3’UTR Markers Are Linked to Gastric Cancer Development and Survival

HLA-G High-expressor 3’UTR Markers Are Linked to Gastric Cancer Development and Survival

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

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

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