Investigation of the IL7Rα Gene Polymorphism rs6897932 and the Expression Levels of the CDH1, TTPAL, and FHIT Genes in Patients with Breast Cancer.

OBJECTIVE: The aim of this study was to determine the expression levels of CDH1, FHIT, and TTPAL genes and to determine the genotype and allele frequencies of the IL7Rα gene polymorphism rs6897932 in patients with breast cancer. METHODS: The expression levels of genes and the distribution of the IL7Rα gene polymorphism rs6897932 were analyzed by real-time polymerase chain reaction. RESULTS: No differences in genotype ratios or allele frequencies were observed between the 2 groups for the IL7Rα gene polymorphism rs6897932. The frequency of the IL7Rα rs6897932 T risk allele was found to be similar between breast cancer patients and controls. CDH1 messenger RNA (mRNA) levels decreased (0.714-fold and 0.834-fold, respectively), and TTPAL mRNA levels increased (2.675-fold [P < .05] and 1.169-fold, respectively) in tumor tissues and peripheral blood samples. FHIT mRNA levels decreased (0.559-fold) in tumor tissue samples and increased (2.21-fold) in peripheral blood samples. CONCLUSION: Our results are compatible with those reported in the literature. It can be suggested that the upregulation observed in the TTPAL gene might be a marker for breast cancer. The downregulation of CDH1 and FHIT gene expression has been validated in our study. An increase in the copy numbers of FHIT mRNA in blood samples and a decrease in the tumor samples can also be considered an abnormal condition.

IL-7/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): a cross-sectional study.

Community-acquired pneumonia (CAP) is a worldwide leading cause of death. Recognized risk factors in some severe cases have not been identified. Lymphocytopenia has been frequently described in CAP. Since IL-7, membrane-bound receptor (IL7Rα;CD127) and soluble IL7Rα (sIL7R) are critical in lymphocytes homeostasis, in this work we aimed to evaluate the involvement of the IL-7/IL7Rα axis in the severity of adult CAP, since it has not been explored. The IL7Rα SNPs rs6897932, rs987106, and rs3194051 SNPs in IL7α were genotyped, the systemic expression of the IL7R gene, sIL7R, IL-7, and levels of peripheral IL7Rα+ T lymphocytes were quantified in 202 hospitalized CAP cases. rs3194051GG was more frequent in non-survivors than in survivors; rs987106TT was more frequent and rs3194051AA less frequent in patients at intensive care unit (ICU) than in those not admitted to ICU. IL7Rα gene expression was lower in non-survivors than in survivors, and in severe than in mild cases. CD3+CD127+ lymphocytes were lower in severe than in mild cases; in non-survivors than in survivors and in ICU than in non- ICU admitted cases. sIL7Rα plasmatic levels were higher in non-survivors than in survivors, and in severe than in mild cases. rs6897932CC, rs987106AA and rs3194051GG carriers showed the highest while rs6897932TT showed the lowest sIL7Rα levels. The AUC of sIL7Rα levels predicting 30-day mortality was 0.71. Plasma IL-7 levels were lower in ICU-admitted than in not ICU-admitted and in non-survivors than in survivors. No additional association was detected. In conclusion, rs3194051GG and rs987106TT IL7R genotypes were associated with a poorer prognosis. A significant association between sIL7R levels and SNPs of the IL7R gene is described for the first time in adult CAP. Increased plasmatic sIL7R could contribute to identifying adult CAP cases at risk of death.

Interleukin 7 receptor alpha Thr244Ile genetic polymorphism is associated with susceptibility and prognostic markers in breast cancer subgroups.

Interleukin-7 (IL-7) exerts crucial functions on lymphoid cells' development and maintenance. In breast cancer (BC), IL-7 promotes growth of tumor cells in culture through the activation of JAK1/3-STAT5 and PI3K/AKT pathways, and expression of IL-7 signaling components was associated with worst prognosis. AC>T polymorphism (rs6897932; Thr244Ile) at exon 6 of IL-7 receptor alpha (IL-7Rα) gene (IL7RA) shifts the balance between the membrane-bound and soluble IL-7Rα splicing variants and was previously associated with autoimmune diseases, but has not been studied in cancer, including BC, so far. Therefore, the present study aimed to investigate the possible association of this polymorphism with the susceptibility and clinicopathological parameters of BC subgroups. IL7RA Thr244Ile was genotyped through PCR-RFLP in 403 women without neoplasia, no personal history of malignancy or family history of BC and in 338 BC patients with clinicopathological data available. BC patients were stratified according to their positivity for estrogen (ER) and/or progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Age-adjusted logistic regression was performed for case-control analyses, and correlations with clinicopathological parameters were assessed through Kendall's Tau-b coefficient. All analyses were two-tailed and had 95% confidence interval. In ER-PR-HER2- BCs, TT genotype was associated with increased susceptibility both in genotypic (TT vs. CC: OR=3.07; CI=1.01-9.38; p=0.05) and recessive (TT vs. CC+CT: OR=3.59; CI=1.19-10.85; p=0.02) models and negatively correlated with disease stage (Tau-b=-0.27; p=0.05). Whereas T allele was positively correlated with histopathological grade (Tau-b=0.29; p=0.03) and lymph node metastasis (Tau-b=0.35; p=0.02) in ER/PR+HER2+BCs and with Ki67 (Tau-b=0.51; p=0.008) in ER-PR-HER2+ subgroup. These data indicate that IL-7Rα is involved in BC, and that IL7RA polymorphism may play distinct roles in breast carcinogenesis according to BC subtype, pointing this genetic variant as an interesting marker for breast carcinogenesis to be validated by further mechanistic and prospective studies with larger samples.

[Altered expression of survival (CD127) and death (Fas) receptors in total, naïve and memory CD8 T lymphocytes from human immunodeficiency virus infected patients: possible implications for progression of infection]. / Expresión alterada de receptores de supervivencia (CD127) y de muerte (Fas) en linfocitos T CD8 totales, virgenes y de memoria de pacientes infectados por el Virus de Inmunodeficiencia Humana: posibles implicaciones para la progresión de la infección.

We studied the ex vivo and in vitro expression of CD95/Fas and CD127 receptors in total, naive and memory CD8+ T cells from HIV infected patients with different blood counts of CD4+ T cells. In addition, spontaneous and induced apoptosis were determined in vitro using a viral antigen (Env), along with an evaluation of their specific proliferative capacity. The obtained results demonstrated that patients with low counts of CD4+ T cells (CD4 < 250/microL), showed ex vivo, a high expression of CD95/Fas and a low expression of CD127 in all CD8+ T cell subgroups, as compared with patients with bigger counts of CD4+ T cells in blood (CD4> 250/microL). In vitro analyses using Env antigen showed that CD8+ T cells displayed a similar expression of both receptors, with a higher incidence of spontaneous and induced apoptosis and a diminished proliferative capacity as compared with controls. Results indicate how the progression of VIH infection in non-treated patients is related to a decrease of CD8+ T cells in blood, characterized by failures in their proliferative capacity and apoptosis frequency, which is demonstrated by the altered expression of CD127 and CD95/Fas expression.