Comparative genomics reveals the acquisition of mobile genetic elements by the plant growth-promoting Pantoea eucrina OB49 in polluted environments.

Heavy metal-tolerant plant growth-promoting bacteria (PGPB) have gained popularity in bioremediation in recent years. A genome-assisted study of a heavy metal-tolerant PGPB Pantoea eucrina OB49 isolated from the rhizosphere of wheat grown on a heavy metal-contaminated site is presented. Comparative pan-genome analysis indicated that OB49 acquired heavy metal resistance genes through horizontal gene transfer. On contigs S10 and S12, OB49 has two arsRBCH operons that give arsenic resistance. On the S12 contig, an arsRBCH operon was discovered in conjunction with the merRTPCADE operon, which provides mercury resistance. P. eucrina OB49 may be involved in an ecological alternative for heavy metal remediation and growth promotion of wheat grown in metal-polluted soils. Our results suggested the detection of mobile genetic elements that harbour the ars operon and the fluoride resistance genes adjacent to the mer operon.

Prognostic significance of high circulating sHLA-G in ovarian carcinoma.

HLA-G is a non-classical major histocompatibility complex class Ib molecule. Its expression has been described in various cancer types, including ovarian cancer. HLA-G molecule has been implicated in immune escape and in progression of ovarian tumor cells. Our goal was to assess if total soluble (s)HLA-G molecules or HLA-G5 and sHLA-G1 isoforms could be considered as circulating ovarian tumor biomarkers, we measured the concentration of these molecules in ovarian carcinoma patients stratified according with their clinicopathological parameters. sHLA-G, sHLA-G1 and HLA-G5 concentrations were dosed in plasma samples by sandwich-ELISA. The sHLA-G dimerization was analyzed after immunoprecipitation and SDS-PAGE migration. Total sHLA-G and sHLA-G1 levels were significantly represented in plasma of ovarian carcinoma patients compared to healthy controls. sHLA-G1 isoform concentration was highly represented in ovarian carcinoma compared to HLA-G5 isoforms. Additionally, high sHLA-G molecules have been found in aged patients, as well as in patients with advanced stages, and those with metastatic lymph nodes and those with distant metastasis. Elsewhere, sHLA-G monomers were highly represented in ovarian carcinoma patients compared to controls. sHLA-G plasmatic protein was highly represented in ovarian carcinoma. In effect, HLA-G might be considered as a new checkpoint molecule that could be used to assess progression and recurrence of the disease, thus placing it as a potential biomarker for advanced and complicated ovarian carcinoma.

Expression analysis of immune-regulatory molecules HLA-G, HLA-E and IDO in endometrial cancer.

HLA-G has been widely implicated in advanced cancers through different pathways of immunosuppression allowing tumor escape. Contrarily, HLA-E has a controversial role in the tumor escape from the immune system. IDO catabolic enzyme is known to be up-regulated in many tumors types allowing their immune escape. Based on these considerations, we investigated the expression of HLA-G, HLA-E and IDO molecules in endometrial cancer (EC) and their association with prognostic clinicopathologic parameters. Their expression were checked in tumoral and adjacent endometrial tissues. Both HLA-G and IDO immunostaining were significantly increased in EC tissues compared to normal residual endometrial glands (Mann Whitney U-test, p = 0.0001 and p = 0,020 respectively). However, HLA-E was highly expressed in tumoral tissues as well as in normal residual endometrial glands (respectively, 100% and 81.8%). Increased HLA-G expression levels were observed in high histological grade (grade 3), and in the non-endometrioid type 2 EC. Unexpectedly, patients with IDO Low expression had significantly impaired overall survival compared to patients with IDO High (log-rank p = 0.021). Conversely, HLA-E low expression was associated to an improved overall survival EC (log-rank p = 0.004). We concluded that, HLA-G and IDO are highly expressed in EC compared to adjacent normal endometrial tissues, that might be interesting for the EC outcome.

HLA-G, HLA-E, and IDO overexpression predicts a worse survival of Tunisian patients with vulvar squamous cell carcinoma.

Little is known about non-classical HLA molecules in vulvar squamous cell carcinoma (VSCC). Because of the indoleamine-2,3-dioxygenase (IDO) immune tolerant role in association with HLA-G, we evaluated the clinical and prognostic value of HLA-G, HLA-E, and IDO in VSCC. HLA-G, HLA-E, and IDO expression was determined by immunohistochemistry in VSCC and associated with clinicopathological parameters and disease outcome. These three molecules were highly represented in tumoral tissues vs healthy matched vulvar tissues (P = 0.0001). Significant differences in HLA-G expression in stages, tumor size, tumor invasion depth, and resection margins subgroups were reported (P < 0.05). At 5 years, the cumulative survival rates was of 79.8% in patients with HLA-Glow expression vs 12.5% in those with HLA-Ghigh expression (P < 3 × 10-5 ). Similarly, patients with IDOhigh expression were at a significantly reduced overall survival (OS) and disease-free survival (DFS) rates (P = 0.011 and 0.045, respectively). The overexpression of the three molecules together worsen survival rates of VSCC patients (OS: P = 0.000038, DFS: P = 0.000085). Altogether, our results showed that HLA-G, HLA-E, and IDO may represent novel candidate markers for patients' prognosis and potential targets for VSCC therapy.

Increased plasmatic soluble HLA-G levels in endometrial cancer.

Human Leukocyte Antigen-G (HLA-G) is known as an immune suppressive molecule; it interacts with several immune cells and inhibits their functions. HLA-G molecule is highly represented in pathological conditions including malignant transformation. To the best of our knowledge this is the first study that focuses on the expression of soluble HLA-G (sHLA-G) in endometrial cancer (EC). We aimed at exploring sHLA-G plasma levels and its prognostic value in EC. We examined total sHLA-G expression as well as the sHLA-G1 and HLA-G5 isoforms expression in plasma samples from 40 patients with EC and 45 healthy controls by a specific sandwich ELISA. Immunoprecipitation and Coomassie blue staining were performed to explore the presence of plasmatic sHLA-G monomers and dimers. sHLA-G plasma level was significantly enhanced in patients with EC compared to healthy controls (p = 0.028). Additionally, HLA-G5 molecules were highly represented than sHLA-G1 molecules in EC, at the borderline of significance (p = 0.061). Interestingly, sHLA-G has been shown to be increased in early stages (Stages I and II) as well as in high grade EC (Grade 3) that is associated with rapid spread of the disease (p = 0.057). sHLA-G positive EC plasma were majorly in monomeric form (75%). Clinically, all the HLA-G dimers were detected in early stages and in high grade of EC. Our data strengthen the implication of HLA-G molecules in EC etiology and especially in progression.

Clinicopathologic significance of HLA-G and HLA-E molecules in Tunisian patients with ovarian carcinoma.

BACKGROUND: The human leukocyte antigen (HLA)-G and HLA-E, non classical HLA class I molecules, have been highly implicated in immune tolerance. HLA-G and HLA-E molecules were proposed as putative markers of several advanced cancers. As a step towards a better understanding of ovarian carcinoma, we evaluated the expression of both HLA-G and HLA-E molecules and explored their prognostic implication. METHODS: HLA-G and HLA-E expression were studied by immunohistochemistry on ovarian carcinoma tissues. This expression was semi-quantitatively scored into four expression groups and correlated to clinicopathological parameters and patients' survival. RESULTS: HLA-G and HLA-E have been found to be highly expressed in ovarian carcinoma tissues (Respectively, 72.4% and 96.8%). They are frequently co-expressed. Univariate and multivariate analysis revealed that a positive HLA-G expression status in tumor tissue is a promising candidate parameter to predict disease recurrence in addition to the disease status in Tunisian patients with ovarian carcinoma. Moreover, the elevated HLA-E expression was associated with serous ovarian carcinoma subtype as well as with advanced stages of ovarian carcinoma. CONCLUSION: HLA-G and HLA-E are highly represented in ovarian carcinoma suggesting a potential association with progressive disease mechanism. HLA-G and HLA-E molecules might be new candidates' markers for ovarian carcinoma progression.

Human leukocyte antigen (HLA-F) polymorphism is associated with chronic HBV infection.

Human leukocyte antigen (HLA)-F has been involved in immune regulation of infectious diseases. However, the role of HLA-F polymorphisms in hepatitis B infection outcomes remains unclear. Here, we aimed to determine HLA-F polymorphism implication in chronic HBV. Genotype analysis was performed for three single nucleotide polymorphisms (SNPs) of HLA-F and one SNP of HLA-E using PCR-SSP, in 252 Tunisian patients with chronic HBV infection stratified according to their HBV DNA levels (140 patients with low HBV DNA levels < 2000 IU/mL and 112 patients with high HBV DNA levels ≥ 2000 IU/mL) and 240 healthy controls (CTRL). The three HLA-F SNPs (HLA-F*01:02, -F*01:03 and -F*01:04) have the same allelic and genotypic frequencies in patients and in CTRL. We reported a low HLA-F*01:02 and F*01:04 allelic frequencies in the Tunisian population; however, high HLA-F*01:03 allele frequencies were observed (17%). A significant association was found between the HLA-F*01:03 allele and decreased level of HBV DNA (P = 0.02 OR 0.56, 95% CI 0.35-0.92). No significant differences were observed in haplotype distribution between patients and CTRL. A significant association of HLA-F*01:03 with the level of HBV DNA suggests an important role of HLA-F in HBV replication control.

Association of HLA-G +3142 C>G polymorphism and breast cancer in Tunisian population.

HLA-G is highly expressed in cancer. Also, it is associated to its progression. Here, we explored the relationship between two HLA-G polymorphisms with breast cancer (BC) and tried to make a correlation with sHLA-G levels. We genotyped 104 patients with BC and 83 controls (CTRL) for HLA-G 14-bp insertion/deletion (Ins/Del) and HLA-G +3142 C>G polymorphisms. The mutations were identified with PCR and PCR-RFLP. The sHLA-G dosage was performed on plasma samples by a specific ELISA. A significant association with BC was found concerning the G allele in the +3142 C>G polymorphism (p = 0.0004). The G/G genotype is the protective genotype (1 % in BC patients vs. 13.1 % in CTRL, OR 0.065, 95 % CI 0.008-0.523). No statistically significant differences were observed for the 14-bp Ins/Del polymorphism between BC patients and controls frequencies. The protection by G/G genotype of +3142 C>G polymorphism is maintained in young patients (<50 years, p = 0.0006) and in early-diagnosed BC patients (<50 years, p = 0.0033). In addition, an association was found between the haplotypes inferred by both HLA-G polymorphisms and BC susceptibility. Indeed, the (DelG) haplotype is found as the protective haplotype against BC (OR 0.269, 95 % CI 0.081-0.895, p = 0.023). The ELISA dosage of sHLA-G revealed increased levels in BC compared to CTRL (p < 0.0001). We demonstrated also that sHLA-G is closely associated with advanced stages of BC without significance. sHLA-G is increased in TNM IV and SBR III subgroups. It is also enhanced in patients with a tumor size over 20 mm and in triple-negative patients. Taken together, our findings demonstrate, for the first time, the association of HLA-G +3142 C>G polymorphism with BC susceptibility in Tunisian population. Our results revealed also a potential implication of sHLA-G in advanced stages of BC.

Pregnancy and breastfeeding: a new theory for sHLA-G in breast cancer patients?

It is now widely recognized that HLA-G molecule is implicated in immune tolerance and particularly in immune subversion of tumor cells. In this study, we explored levels of soluble HLA-G (sHLA-G) in plasma samples obtained from women with breast cancer (BC). Additionally, we correlated sHLA-G concentration with pregnancy and breastfeeding history. We reported in this preliminary work significant differences in sHLA-G levels between BC patients with/without breastfeeding experience (p = 0.04). Interestingly, among women with BC, only those without previous pregnancy experience present significant increase in sHLA-G (p = 0.02). Of relevance, we demonstrated that patients without both pregnancy and breastfeeding history have advanced SBR III grade, associated with significant enhancement in tumor size compared with patients who had both experiences (p = 0.028). Taken together, our results indicate the potential implication of previous pregnancy and breastfeeding experience in sHLA-G expression during BC. We theorized that having pregnancy and breastfeeding history may protect against advanced BC stages.

Association between sHLA-G and HLA-G 14-bp deletion/insertion polymorphism in Crohn's disease.

The aim of this study was to evaluate the association between the HLA-G 14-bp deletion/insertion (Del/Ins) polymorphism and soluble (s) HLA-G production in patients with Crohn's disease (CD). We analyzed also the sHLA-G molecules by ELISA and western blot in plasma samples. Among unselected patients, the 14-bp Del/Ins polymorphism was not significantly associated with increased CD risk neither for alleles (P = 0.371) nor for genotypes (P = 0.625). However, a significant association was reported between the 14-bp Del/Ins polymorphism and CD, in particular in young-onset CD patients for alleles [P = 0.020, odds ratio (OR) = 2.438, 95% confidence interval (CI): 1.13-5.25] but not with adult-onset CD patients. A significant association was reported concerning the genotype Ins/Ins for young-onset CD patients (P = 0.029, OR = 3.257, 95% CI: 1.08-9.77). We observed also a significant increase in sHLA-G measured by ELISA in CD patients compared to controls (P = 0.002). The 14-bp Del/Del and 14-bp Del/Ins genotypes are the high HLA-G producers. Among sHLA-G(positive) patients, 43% of subjects present dimers of HLA-G. The presence of dimers seems to be related to the advanced stages of the disease. The 14-bp Del/Ins polymorphism is associated with an increased risk of CD particularly in young-onset CD patients and controls sHLA-G plasma levels. Dimers of sHLA-G are frequent in advanced disease stages. The above findings indicate that the genetic 14-bp Del/Ins polymorphism in exon 8 of the HLA-G gene is associated with the risk of CD and suggest a role for sHLA-G as a prognostic marker for progressive disease.