A Novel Exon 2 Deletion Mutation in the GRXCR1 Gene Associated With Non-Syndromic Hearing Loss: A Case Report and Review of Literatures.

BACKGROUND: About 80% of congenital hearing loss cases have genetic causes, often autosomal recessive and non-syndromic. Autosomal Recessive Non-syndromic hearing loss is characterized by extreme genetic heterogeneity. OBJECTIVES: To report a case of congenital hearing loss with novel homozygous deletion in GRXCR1 gene. METHODS: Case reports and review of literatures. RESULTS: In this study, the proband was a 32-year-old woman seeking pre-marriage genetic counseling with non-syndromic congenital hearing loss. An owing negative test for GJB2 mutations, she underwent exome sequencing, unveiling a novel homozygous exon 2 deletion of the GRXCR1 gene. This mutation was confirmed in her affected mother and sibling by PCR and Quantitative Real-Time PCR. CONCLUSION: We identified a novel GRXCR1 gene mutation related to congenital hearing loss in a family. Our study highlights the efficiency of exome sequencing in discovering gene mutations in cases of diseases with genetic heterogeneity.

Clinicopathological and prognostic value of lncRNA TPT1-AS1 in cancer: A systematic review study and meta-analysis.

INTRODUCTION: Aberrant expression of lncRNAs in cancer cells can impact their key phenotypes. We aimed to summarize available evidence on clinicopathological and prognostic value of lncRNA TPT1-AS1 in cancer. METHODS: A systematic search was performed on Medline and Embase databases using relevant key terms covering lncRNA TPT1-AS1, cancer, and clinical outcomes. The effect size estimates and their 95 % confidence interval (CI) were pooled using random-effects models. Meta- analyses were conducted using STATA 16.0 software. RESULTS: Seventeen articles met our eligibility criteria. Tumor tissue compared to normal tissue showed increased level of lncRNA TPT1-AS1 expression (pooled standardized mean difference (95 % CI): 0.65 (0.52-0.79)). Overexpression of this lncRNA was a significant predictor for poor prognosis (Pooled log-rank test P-value < 0.001); in patients with high-level of lncRNA TPT1-AS1, the risk of death at five years was 1.40 times greater than their counterparts. The pooled Odds ratios for association lncRNA TPT1-AS1 with tumor stage, tumor size, and lymph node metastasis were 1.94 (95 % CI: 0.90-4.19, 8 studies, I2 = 79.6 %), 2.33 (95 % CI: 1.31-4.14, 5 studies, I2 = 40.0 %), and 1.89 (95 % CI: 1.08-3.36, 5 studies, I2 = 61.7 %), respectively. Regarding the identified potential mechanisms, lncRNA TPT1-AS1 plays a role in cancer growth mainly by sponging miRNAs and regulating their downstream targets or controlling the expression of key cell cycle regulators. CONCLUSION: In cancer patients, elevated expression of lncRNA TPT1-AS1 might be associated with a shorter Overall Survival, advanced stages, larger tumor size, and lymph node metastasis.

Psychological problems and reduced health-related quality of life in the COVID-19 survivors.

BACKGROUND: COVID-19 survivors are predicted to experience the long-term consequences, including pulmonary, neurologic, cardiovascular, and mental health sequelae. This systematic review and meta-analysis was performed on studies assessing the health-related quality of life (HRQoL) and psychiatric problems in COVID-19 survivors. METHODS: A systematic search was performed on PubMed, Embase, and Google scholar databases using key terms COVID-19, PTSD, depression, anxiety, HRQoL, survivors. Pooled estimates were calculated using the random-effects models. RESULTS: A total of 21 eligible articles were included. The pooled prevalence of PTSD, depression, and anxiety among COVID-19 survivors were 18% (95% CI: 13 to 23%, I2=88.23%), 12% (8 to 17%, I2=91.84%), and 17% (12 to 22%, I2=97.07%), respectively. COVID-19 survivors compared to pre-COVID-19 time and controls showed reduced HRQoL and a lower score in Social Functioning (SF) and Role Physical (RP), and Role Emotional (RE) health. Females compared to males had a higher risk of experiencing mental health problems. Also, patients with severe disease had a higher prevalence of depression and anxiety, but not PTSD. LIMITATIONS: Regarding HRQoL, we were not able to perform a subgroup analysis due to a lack of data. Also, the included studies mainly used a self-rating scale to detect psychological problems in their study population. CONCLUSION: A significant number of patients who survived from COVID-19 might suffer from PTSD, depression, and anxiety beyond one month. Our systematic review also found evidence of reduced HQOL and limited social role in these survivors.

C-X-C Chemokine Receptor Type 7 (CXCR-7) Expression in Invasive Ductal Carcinoma of Breast in Association with Clinicopathological Features.

C-X-C chemokine receptor type 7 (CXCR-7) is an atypical receptor for chemokines whose role in different stages of carcinogenesis has been evaluated in breast cancer cell lines and animal models. Moreover, it has been demonstrated to be a target of regulation by the tumor suppressor microRNA (miR)-100. In the present study, we assessed CXCR-7 expression in 60 breast cancer patients in association with clinicopathological and demographic data of patients. We also extracted the results of our previous work on miR-100 expression in the same cohort of patients to assess the correlation between miR-100 and CXCR-7 expression levels. Transcript levels of CXCR-7 were significantly higher in tumoral tissues compared with adjacent non-cancerous tissues (ANCTs) (Tumoral vs. ANCTs: 3.64 ± 1.8 vs. 0.73 ± 1.3, P = 0.000). A significant negative correlation was detected between CXCR-7 protein and miR-100 transcript levels (r = -0.526, P < 0.05). High CXCR-7 mRNA levels were significantly associated with tumor size (P = 0.01). Besides, high protein levels were more prevalent in higher TNM stages (P = 0.000). Moreover, high CXCR-7 protein levels were significantly associated with ER (P = 0.005) and PR (P = 0.02) status. The present work provides further evidence for the role of CXCR-7 in breast cancer and proposes the elimination of inhibitory effects of miR-100 on CXCR-7 expression as a mechanism for its up-regulation in breast cancer tissues.

Expression analysis of selected miR-206 targets from the transforming growth factor-ß signaling pathway in breast cancer.

Breast cancer as a molecularly heterogeneous malignancy is associated with dysregulation of several signaling pathways, including transforming growth factor-ß (TGF-ß) signaling. On the other hand, several recent studies have demonstrated the role of microRNAs (miRNAs) in breast cancer pathogenesis. In the current study, we performed a computerized search to find miR-206 target genes that are functionally linked to the TGF-ß signaling pathway. We selected LEF1, Smad2, and Snail2 genes to assess their expression in 65 breast cancer samples and their adjacent noncancerous tissues (ANCTs) in correlation with expression levels of miR-206 as well as clinicopathological characteristics of patients. miR-206 was significantly downregulated in (Estrogen receptor) ER-positive breast cancer samples compared with their corresponding ANCTs. Association analysis between expression levels of genes and demographic features of patients showed significant association between expressions of SMAD2 and LEF1 genes and body mass index ( P values of 0.03 and 0.02, respectively). miR-206 low-expression levels were associated with TNM stage, mitotic rate, and lymph node involvement ( P values of 0.02, 0.01, and 0.01 respectively). In addition, SMAD2 high-expression levels were associated with HER2 status ( P = 0.02). Consequently, our data highlight the role of TGF-ß signaling dysregulation in the pathogenesis of breast cancer and warrant further evaluation of miRNAs and messenger RNA coding genes in this pathway to facilitate detection of cancer biomarkers and therapeutic targets.

Neuropilin-1 expression is associated with lymph node metastasis in breast cancer tissues.

PURPOSE: Neuropilin-1 (NRP1) as an isoform-specific receptor for vascular endothelial growth factor and placenta growth factor in endothelial cells has been demonstrated to be expressed in breast cancer cells where it plays functional roles in cell survival, invasion, and migration. We hypothesized that an expression of NRP1 in breast cancer tissues is associated with clinicopathological data of patients and expression of the tumor suppressor miR-206. PATIENTS AND METHODS: We evaluated the expression of NRP1 in 48 invasive ductal carcinomas of the breast and their corresponding adjacent noncancerous tissues (ANCTs) by means of real-time polymerase chain reaction. We also extracted data on miR-206 gene expression from the same cohort of patients to evaluate the correlation between expression levels of miR-206 and NRP1. In addition, we quantified NRP1 protein levels using the enzyme-linked immunosorbent assay technique. RESULTS: No significant difference was found in NRP1 expression between tumoral tissues and ANCTs. We also assessed the associations between expression levels of NRP1 and clinicopathological data of patients and found no significant associations between NRP1 transcript levels and any characteristic. However, NRP1 protein concentrations were significantly higher in patients with lymph node involvement compared with those without lymph node involvement. No correlation was found between NRP1 and miR-206 expression levels. CONCLUSION: NRP1 protein levels might be an indicator of metastasis potential in breast cancer. Future studies are needed to confirm these results in larger cohorts of patients.

Application of cancer-testis antigens in immunotherapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a worldwide common malignancy with poor prognosis. Several studies have aimed at identification of appropriate biomarkers for early detection of this cancer. Cancer-testis antigens (CTAs) as a novel group of tumor-associated antigens have been demonstrated to be expressed in HCC samples as well as peripheral blood samples from these patients but not in the corresponding adjacent noncancerous samples. Such pattern of expression has provided them an opportunity to be used as immunotherapeutic targets. The detection of spontaneous immune responses against CTAs in HCC patients has prompted design of CTA-based immunotherapeutic protocols in these patients. The results of some clinical trials have been promising in a subset of patients.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: report of three cases from Iran.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also named as autoimmune polyglandular syndrome (APS) type 1, is a rare autosomal recessive disorder caused by mutations in autoimmune regulator (AIRE) gene. It is distinguished by an immune-mediated damage of endocrine tissues, chronic candidiasis, and ectodermal disorder. APECED has been shown to be frequent in some populations including Iranian Jews. Here we report three cases of APECED from two independent Iranian Muslim families. Addison's disease, hypoparathyroidismand mucocutaneous candidiasis were shared clinical manifestations in all patients. Mutational analyses have demonstrated a novel homozygous splice site mutation (c.1095+2T>A) in intron 9 and a previously identified homozygous nonsense mutation (c.415C>T) in exon 3 of patients respectively. Future studies are needed to evaluate the frequency of these variants in Iranian APECED patients which would facilitate genetic counseling as well as prenatal diagnosis.

Immunotherapy in Multiple Myeloma Using Cancer-Testis Antigens.

CONTEXT: Multiple myeloma (MM) is a B-cell malignancy characterized by monoclonal expansion of abnormal plasma cells in the bone marrow. It accounts for 10% of hematological malignancies. Although patients respond to a wide range of anticancer modalities, relapse occurs in a significant number of the cases. Immunotherapeutic approaches have been evolved to tackle this problem. Cancer-testis antigens CTAs as a group of tumor-associated antigens are appropriate targets for cancer immunotherapy as they have restricted expression pattern in normal tissues except for testis which is an immune-privileged site. Expression of these antigens has been assessed in different malignancies including MM. EVIDENCE ACQUISITION: We performed a computerized search of the MEDLINE/PubMed databases with key words: multiple myeloma, cancer-testis antigen, and cancer stem cell and immunotherapy. RESULTS: Several CTAs including NY-ESO-1, MAGE and GAGE family have been shown to be expressed in MM patients. Cellular and humoral immune responses against these antigens have been detected in MM patients. CONCLUSIONS: The frequent and high expression level of CTAs in MM patients shows that these antigens can be applied as cancer biomarkers as well as targets for immunotherapy in these patients.

Cancer-testis genes as candidates for immunotherapy in breast cancer.

Cancer-testis (CT) antigens are tumor-associated antigens attracting immunologists for their possible application in the immunotherapy of cancer. Several clinical trials have assessed their therapeutic potentials in cancer patients. Breast cancers, especially triple-negative cancers are among those with significant expression of CT genes. Identification of CT genes with high expression in cancer patients is the prerequisite for any immunotherapeutic approach. CT genes have gained attention not only for immunotherapy of cancer patients, but also for immunoprevention in high-risk individuals. Many CT genes have proved to be immunogenic in breast cancer patients suggesting the basis for the development of polyvalent vaccines.

Expression analysis of two cancer-testis genes, FBXO39 and TDRD4, in breast cancer tissues and cell lines.

Breast cancer accounts for one third of new cancer cases among women. The need for biomarkers for early detection is the stimulus to researchers to evaluate altered expression of genes in tumours. Cancer-testis (CT) genes are a group with limited expression in normal tissues except testis but up-regulation in a wide variety of cancers. We here evaluated expression of two CT genes named FBXO39 and TDRD4 in 32 invasive ductal carcinoma samples, 10 fibroadenomas and 6 normal breast tissue samples, in addition to two breast cancer cell lines, MCF-7 and MDA-MB-231, by the means of quantitative real time RT-PCR. FBXO39 showed significant up-regulation in invasive ductal carcinoma samples in comparison with normal samples. It also was expressed in both cell lines and after RHOXF1 gene knock down it was down-regulated in MCF-7 but up-regulated in the MDA-MB-231 cell line. TDRD4 was not expressed in the MCF-7 cell line and any of the tissue samples except testis. However, it was expressed in MDA-MB-231 and was up-regulated after RHOXF1 gene knock down. Our results show that FBXO39 but not TDRD4 can be used for cancer detection and if proved to be immunogenic, might be a putative candidate for breast cancer immunotherapy.