Associations of HLA-G 3’UTR polymorphisms and increased HLA-G expression with gastric cancer susceptibility and prognosis
Background: Gastric cancer (GC) remains a serious health concern and is characterized by a multifactorial etiology involving both genetic and epigenetic factors. The aim of the current study was to examine the relationship between Human leukocyte antigen (HLA)-G 3’UTR polymorphisms and the expressio...
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Elsevier
2025-01-01
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| Series: | Immunobiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171298524000822 |
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| author | Ines Zemni Daria Bortolotti Sabrine Dhouioui Sana Baroudi Malek Ferjani Inès Nasri Yosr Zenzri Md Ataur Rahman Abdel Halim Harrath Roberta Rizzo Nadia Boujelbene Inès Zidi |
| author_facet | Ines Zemni Daria Bortolotti Sabrine Dhouioui Sana Baroudi Malek Ferjani Inès Nasri Yosr Zenzri Md Ataur Rahman Abdel Halim Harrath Roberta Rizzo Nadia Boujelbene Inès Zidi |
| author_sort | Ines Zemni |
| collection | DOAJ |
| description | Background: Gastric cancer (GC) remains a serious health concern and is characterized by a multifactorial etiology involving both genetic and epigenetic factors. The aim of the current study was to examine the relationship between Human leukocyte antigen (HLA)-G 3’UTR polymorphisms and the expression of HLA-G in both tumor tissues and plasma samples from patients with GC in the Tunisian population. Methods: HLA-G 3’UTR polymorphisms (14pb Insertion/deletion and + 3142C/G) were identified by polymerase chain reaction (PCR) or Sanger sequencing. Plasma levels of sHLA-G (total sHLA-G, shed HLA-G1 and HLA-G5) were determined. Immunohistochemistry was used to evaluate the expression of HLA-G in tumor tissues. Results: The Del/Del genotype and Del allele frequencies were different between GC patients and healthy donors (HD) (OR [95 % CI] = 2.483 [1.070–5.410], p = 0.025 vs. OR [95 % CI] = 1.537 [0.924–2.584], p = 0.099; respectively). The C/C genotype and C allele frequencies were significantly greater in GC patients than in HD (OR [95 % CI] = 2.269[0.1.070–4.904], p = 0.033 vs. OR [95 % CI] = 1.746[1.045–2.878], p = 0.034; respectively). Interestingly, the Del/Del genotype and Del allele were significantly associated with an increased risk of GC in patients aged ≥55 years at diagnosis. HLA-G was highly expressed in GC tissues, particularly in tissues with advanced tumor invasion (T3 + T4). Compared with HD, GC patients had higher soluble HLA-G, shed HLA-G1 and HLA-G5 levels (Mann-Whitney: p = 0.001, p = 0.001 and p = 0.643, respectively). Assessment of patients' survival by Kaplan-Meier analysis indicated that the Del allele was significantly associated with reduced overall survival (OS) in GC patients at advanced stages III + IV (p = 0.043). Conclusions: These results suggest that HLA-G 3’UTR polymorphisms are associated with GC susceptibility in Tunisian population. The expression of HLA-G in both the tissue and plasma may play an important role in the development and progression of GC. Therefore, the current study supported the recommendation of investigating HLA-G 3’UTR polymorphisms in GC and indicated that HLA-G molecules could serve as promising therapeutic targets in GC. |
| format | Article |
| id | doaj-art-84e523e6aa904f78b77835c2852f42a4 |
| institution | Kabale University |
| issn | 0171-2985 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Immunobiology |
| spelling | doaj-art-84e523e6aa904f78b77835c2852f42a42025-01-27T04:21:42ZengElsevierImmunobiology0171-29852025-01-012301152864Associations of HLA-G 3’UTR polymorphisms and increased HLA-G expression with gastric cancer susceptibility and prognosisInes Zemni0Daria Bortolotti1Sabrine Dhouioui2Sana Baroudi3Malek Ferjani4Inès Nasri5Yosr Zenzri6Md Ataur Rahman7Abdel Halim Harrath8Roberta Rizzo9Nadia Boujelbene10Inès Zidi11Laboratory of Microorganisms and Active Biomolecules (LR03ES03), Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia; Department of Surgical Oncology, Salah Azaiez Institute, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, TunisiaDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, Ferrara, ItalyLaboratory of Microorganisms and Active Biomolecules (LR03ES03), Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Microorganisms and Active Biomolecules (LR03ES03), Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Microorganisms and Active Biomolecules (LR03ES03), Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, TunisiaDepartment of Pathology, Salah Azaiez Institute, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, TunisiaDepartment of Oncology, Salah Azaiez Institute, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, TunisiaDepartment of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of KoreaKing Saud University, College of Science, Department of Zoology, 11451 Riyadh, Saudi ArabiaDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, Ferrara, ItalyDepartment of Pathology, Salah Azaiez Institute, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, TunisiaLaboratory of Microorganisms and Active Biomolecules (LR03ES03), Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia; Corresponding author at: Université de Tunis El Manar, Faculté des Science de Tunis, LR03ES03 Laboratoire des Microorganismes et Biomolécules Actives, 2092 Tunis, Tunisia.Background: Gastric cancer (GC) remains a serious health concern and is characterized by a multifactorial etiology involving both genetic and epigenetic factors. The aim of the current study was to examine the relationship between Human leukocyte antigen (HLA)-G 3’UTR polymorphisms and the expression of HLA-G in both tumor tissues and plasma samples from patients with GC in the Tunisian population. Methods: HLA-G 3’UTR polymorphisms (14pb Insertion/deletion and + 3142C/G) were identified by polymerase chain reaction (PCR) or Sanger sequencing. Plasma levels of sHLA-G (total sHLA-G, shed HLA-G1 and HLA-G5) were determined. Immunohistochemistry was used to evaluate the expression of HLA-G in tumor tissues. Results: The Del/Del genotype and Del allele frequencies were different between GC patients and healthy donors (HD) (OR [95 % CI] = 2.483 [1.070–5.410], p = 0.025 vs. OR [95 % CI] = 1.537 [0.924–2.584], p = 0.099; respectively). The C/C genotype and C allele frequencies were significantly greater in GC patients than in HD (OR [95 % CI] = 2.269[0.1.070–4.904], p = 0.033 vs. OR [95 % CI] = 1.746[1.045–2.878], p = 0.034; respectively). Interestingly, the Del/Del genotype and Del allele were significantly associated with an increased risk of GC in patients aged ≥55 years at diagnosis. HLA-G was highly expressed in GC tissues, particularly in tissues with advanced tumor invasion (T3 + T4). Compared with HD, GC patients had higher soluble HLA-G, shed HLA-G1 and HLA-G5 levels (Mann-Whitney: p = 0.001, p = 0.001 and p = 0.643, respectively). Assessment of patients' survival by Kaplan-Meier analysis indicated that the Del allele was significantly associated with reduced overall survival (OS) in GC patients at advanced stages III + IV (p = 0.043). Conclusions: These results suggest that HLA-G 3’UTR polymorphisms are associated with GC susceptibility in Tunisian population. The expression of HLA-G in both the tissue and plasma may play an important role in the development and progression of GC. Therefore, the current study supported the recommendation of investigating HLA-G 3’UTR polymorphisms in GC and indicated that HLA-G molecules could serve as promising therapeutic targets in GC.http://www.sciencedirect.com/science/article/pii/S0171298524000822HLA-GsHLA-GGastric cancerGene polymorphismHLA-G 14pb Ins/DelHLA-G + 3142C/G |
| spellingShingle | Ines Zemni Daria Bortolotti Sabrine Dhouioui Sana Baroudi Malek Ferjani Inès Nasri Yosr Zenzri Md Ataur Rahman Abdel Halim Harrath Roberta Rizzo Nadia Boujelbene Inès Zidi Associations of HLA-G 3’UTR polymorphisms and increased HLA-G expression with gastric cancer susceptibility and prognosis Immunobiology HLA-G sHLA-G Gastric cancer Gene polymorphism HLA-G 14pb Ins/Del HLA-G + 3142C/G |
| title | Associations of HLA-G 3’UTR polymorphisms and increased HLA-G expression with gastric cancer susceptibility and prognosis |
| title_full | Associations of HLA-G 3’UTR polymorphisms and increased HLA-G expression with gastric cancer susceptibility and prognosis |
| title_fullStr | Associations of HLA-G 3’UTR polymorphisms and increased HLA-G expression with gastric cancer susceptibility and prognosis |
| title_full_unstemmed | Associations of HLA-G 3’UTR polymorphisms and increased HLA-G expression with gastric cancer susceptibility and prognosis |
| title_short | Associations of HLA-G 3’UTR polymorphisms and increased HLA-G expression with gastric cancer susceptibility and prognosis |
| title_sort | associations of hla g 3 utr polymorphisms and increased hla g expression with gastric cancer susceptibility and prognosis |
| topic | HLA-G sHLA-G Gastric cancer Gene polymorphism HLA-G 14pb Ins/Del HLA-G + 3142C/G |
| url | http://www.sciencedirect.com/science/article/pii/S0171298524000822 |
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