Interferon-induced transmembrane protein 3 in hepatocellular carcinoma patients.

OBJECTIVE: The study aimed to investigate the over expression of IFITM3 in hepatocellular carcinoma Egyptian patients. BACKGROUND: Hepatocellular carcinoma (HCC) continues to be a serious disease burden. Interferon Induced Transmembrane protein 3 (IFITM3) is a protein that encoded in humans by the IFITM3 gene. It plays a critical role in the immune system's defense, responsible for a large portion of the antiviral activity. In this study, we showed that IFITM3 rs 12252-CC was over expressed in HCC patients compared to control group with HCV infection. METHOD: DNA sequencing was applied for detection of IFITM3 rs 12252-CC and IFITM3 protein level was measured by ELISA to 50 patients with HCC with cirrhosis and 50 with Hepatitis C virus infection. RESULTS: The obtained results of this study indicated that IFITM3 rs 12252-CC was significantly elevated in HCC group, the codominant model of CC genotype of IFITM3 gene had high association with risk of hepatocellular carcinoma with odd ratio (OR) = 2.70, p = 0.041. CONCLUSION: IFITM3 play an important role in progression of hepatocellular carcinoma. Results revealed that IFITM3 rs 12252-CC among Hepatocellular carcinoma patients would allow diagnosis and starting intervention.

Breast cancer risk is associated with the HULC rs7763881, MTMR3 rs12537 polymorphisms, and serum levels of HULC and MTMR3 in Egyptian patients.

BACKGROUND: Highly upregulated in liver cancer (HULC) is one of the LncRNAs that was documented to enhance cancer progression, and its downregulation is associated with cell cycle arrest and apoptosis. Myotubularin-related protein 3 (MTMR3) is required for autophagy, and many studies consider MTMR3 to be a negative regulator of autophagy processes. However, nothing is understood about how they regulate breast cancer. MATERIAL AND METHODS: This case-control study included 245 patients (Group A: 85 early BC Group B: 40 metastatic BC cases, Group C: 40 fibroadenoma cases; and Group D: 80 age matched healthy control subjects. TaqMan Real-time PCR was used to analyse rs7158663 and rs12537. MTMR3 and HULC gene expression levels were measured using RT-PCR. RESULT: Breast cancer patients exhibited elevated serum MTMR3 and HULC compared to fibroadenomas and control cases. The MTMR3 rs12537 "T/T" genotype was highly expressed in cases of breast cancer (early and metastatic) compared to controls (risk genotype). On the other hand, the HULC rs7158663 genotypes were not statistically associated with breast cancer. However, when compared to the control, the C/C genotype of the HULC gene is higher in the case.MTMR3 gene expression was higher in the T/T genotype compared to both the C/C and C/T genotypes, while HULC gene expression was lower in the A/C genotype compared to both the A/A and C/C genotypes. Positive correlation between MTMR3 and HULC. MTMR3 and ALT, as well as HULC and alkaline phosphatase, both showed a statistically significant positive correlation. CONCLUSION: Our findings reveal that MTMR3 and HULC serum expression and their SNPs (HULC rs7763881, MTMR3 rs12537) are associated with a higher risk for the development of breast cancer in the Egyptian population.

PDL-1 expression in lung carcinoma and its correlation with clinicopathological and prognostic characteristics.

Lung cancers have high incidence and high mortality rates. The immune checkpoints as programmed death ligand 1 (PDL-1) can suppress the tumor immune reaction. So, their blocking seems to be a way to treat tumors. This study assesses PDL-1 immunohistochemical expression in lung cancer, and its correlation with prognosis. It included 62 specimens of lung cancer in Hospitals of Mansoura Faculty of Medicine, Egypt. Seventy-one percent of cases showed positive PDL-1 and about 59.1% of them showed high expression. PDL-1 expression in NSCLC was significantly higher than in SCLC (P = 0.019). There were no significant associations between PDL-1 expression and other clinicopathological parameters. A significant mild positive correlation between PDL-1 and EGFR marker was found (P = 0.006). The mean overall survival in cases with positive PDL-1 was lower than negative cases (P = 0.37). Also, progression-free survival was lower among PDL-1 positive cases compared to negative cases (P = 0.5). This study reports that immune checkpoint, PDL-1 is overexpressed in lung cancer especially NSCLC. It is correlated with EGFR overexpression. PDL-1 could have potential to be an effective immune target for lung cancer immunotherapy. But the presence of PD-L1-negative tumors highlights the importance of searching for alternative or combination treatment strategies.Abbreviations: AC: Adenocarcinoma; COPD: Chronic Obstructive Pulmonary Diseases; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; EGFR: Epidermal Growth Factor Receptor; IHC: Immunohistochemical; NSCLC: Non-Small Cell Lung Cancer; OS: Overall Survival; PD1: Programmed Death 1; PDL-1: Programmed Death ligand 1; PFS: Progression Free Survival; SCC: Squamous cell carcinoma; SCLC: Small Cell Lung Cancer; SD: Standard Deviation; TCR: T-cell receptor; TPS: Tumor Proportion Score.

High FOXA1 immunohistochemical expression level associates with mucinous histology, favorable clinico-pathological prognostic parameters and survival advantage in epithelial ovarian cancer.

BACKGROUND: Forkhead box (FOX) A1 is a potential therapeutic biomarker that has been investigated in various human cancers. Limited data exist about FOXA1 biologic role in epithelial ovarian cancer (EOC). AIM: This study assessed FOXA1 immunohistochemical (IHC) expression and evaluated its association with clinico-pathological parameters in EOC including overall and disease-free survivals (OS, DFS) and patient's outcome. METHODS: Patient's socio-epidemiologic, clinical, radiological, laboratory, surgical, and follow-up data were collected. After histopathologic typing, grading and staging, FOXA1 IHC expression was scored in 98 EOC specimens. Clinico-pathological associations were investigated in high-and low-FOXA1 expression groups using appropriate statistical methods. Kaplan-Meier method was used for survival analysis. RESULTS: FOXA1 tumor cell nuclear staining was detected in 63.3% of EOC with weak, moderate and strong scores (28.6%, 12.2% and 22.5% respectively). Comparing high- and low-expression groups (34.7% and 65.3% respectively), high FOXA1 was associated with larger tumors, low mean serum CA-125, tumor histopathology (mucinous and low-grade serous), type I EOC, limited tumor's anatomical extent, absence of nodal or distant metastases and omental nodules, earlier FIGO stages, non-recurrent tumors and survival advantage with longer and OS and DFS (all p ≤ 0.05). Independent predictors of high FOXA1 expression included: omental nodules, tumor's anatomical extent and tumor's size (p ≤ 0.001, = 0.046 and = 0.023 respectively). CONCLUSION: FOXA1 is frequently expressed in EOC notably mucinous and low-grade serous carcinomas in association with favorable prognostic clinico-pathological parameters and longer OS and DFS. It likely has a suppressor function in EOC and could be recommended as a prognostic and therapeutic biomarker.

Association of lncRNA MEG3 Rs7158663 Polymorphism and Serum Expression with Colorectal Cancer in Egyptian Patients.

Background: Colorectal cancer (CRC) is considered the third most common cancer around the world and second in terms of mortality. A significant aspect in its development is genetics. The risk of CRC and other clinicopathologic characteristics were investigated in this work in relation to the long non-coding RNA (lncRNA) MEG3 rs7158663 polymorphism, MEG3 expression, in an Egyptian population. Methods: 160 CRC patients and 160 healthy controls were enrolled in this case-control study. The lncRNA MEG3 rs7158663 was examined using TaqMan Real-time PCR. RT-PCR was used to assess the levels of serum MEG3 expression. Results: A significant higher expression of 'A' allele (risk allele) and A/A genotype in CRC cases vs. control subjects (P <0.001) Participants with A/A genotype had 4.8 times higher odds to exhibit CRC. Serum MEG3 gene expression was generally low in CRC patients, and it was considerably lower in those with the rs7158663 AA genotype than those with the GG genotype (P <0.001). It was found that CRC patients with the rs7158663 GA genotype had lower serum MEG3 expression levels than those with the GG genotype (P <0.001). Conclusions: MEG3 low expression and MEG3 rs7158663 (AA) were associated with CRC risk in Egyptian patients and may serve as a diagnostic and prognostic marker for CRC patients.

Relationship between interferon-induced transmembrane protein 3 and matrix metalloproteinase-9 gene polymorphisms in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma originates from hepatocytes as a result of the effects of numerous genetic variations. Interferon-Induced Transmembrane protein 3 (IFITM3) is involved in the processes of cellular differentiation, apoptosis, cell adhesion, and immune cell regulation. Matrix Metalloproteinase-9 (MMP-9) are zinc dependent endopeptidases that cleave extracellular matrix contents and play an important role in the progression of cancer. OBJECTIVE: The study aimed to outline the key molecular biology progression in hepatocellular carcinoma and the relationship between hepatocellular cancer and genetic polymorphisms of IFITM3 and MMP-9. METHODS: In total 200 patients with hepatocellular carcinoma patients (n=100) and a control group with Hepatitis C virus (n=100) which collected randomly from the EL-Mansoura oncology center during the interval between June 2020 and October 2021. The expression of MMP-9 and the IFITM3 SNP was investigated. MMP-9 gene polymorphisms were estimated by using PCR-RFLP and IFITM3 gene was detected using DNA sequencing, ELISA was used to measure protein levels of MMP-9 and IFITM3. RESULTS: The T allele of MMP-9 was more frequent among patients (n=121) than control subjects (n=71). The C allele of IFITM3 was more frequent among patients (n=112) than control subjects (n=83), polymorphisms of the genes linked to a high risk of disease development, patients of MMP-9 (TT genotype), odd ratio (OR) = 2.63, IFITM3 (CC genotype), OR= 2.43. CONCLUSIONS: We found that the genetic polymorphisms of MMP-9 and IFITM3 are related to the occurrence and development of hepatocellular carcinoma. This study might be utilized in clinical diagnosis and therapy and to provide a baseline for prevention.

Emerging role of exosomes and exosomal microRNA in cancer: pathophysiology and clinical potential.

BACKGROUND: Exosomes are extracellular nanometric vesicles used by cells to communicate with each other. They are responsible for many pathological conditions, including tumors by transferring regulatory biomolecules that impact target cell activity. Because of their high concentration in exosomes compared with parental cells and the rest of exosomal content, specificity to the cell of origin, and their well-organized sorting mechanism, microRNAs (miRNAs) are thought to be the most potent exosomes cargo and used by scientists to track exosomes and to detect cell activity changes and prognosis in cancer early. PURPOSE: In this review, the results of studies examining the role of exosomes in cancer pathophysiology and their clinical potential are discussed in detail. Tumor-derived exosomes (TDEs) mediate the dynamic changes of cancer growth and invasion, including local microenvironment remodeling, distance metastasis, angiogenesis, and tumor-associated immunosuppression. They also contribute to hypoxia-induced tumor progression and cancer cell drug resistance. As a result of exosomes being present in all body fluids, it is possible to have early accessible and less-invasive diagnostic and prognostic measures by forming a table for each cancer type and its matched specific miRNAs. Under testing, available therapeutic uses of exosomes include interference of exosomes biogenesis, secretion, or uptake, and recruitment of exosomes as target-specific drug delivery vehicles, and immunostimulatory agents for both cancer patients and healthy population to avoid cancer development from the start. CONCLUSION: These data suggest that exosomes and exosomal microRNA are directly related to cancer progression mechanisms, and could be used in cancer early diagnosis, prognosis, and therapy.

Human Endogenous Retrovirus-H Long Terminal Repeat- Associating Protein 2 (HHLA2) is a Novel Immune Checkpoint Protein in Lung Cancer which Predicts Survival.

ackground: Lung cancer is one of the most frequently diagnosed malignancies. Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a recently discovered ligand of the B7 family. Blocking this immune checkpoint has become an important treatment option for lung cancer. METHODS: The study includes 62 biopsy specimens either bronchoscopic or CT-guided biopsies diagnosed as lung cancer in Hospitals of Faculty of Medicine, Mansoura University, Egypt during the period from 2016 to 2020. Immunohistochemical Staining for HHLA2 and EGFR was performed. HHLA2 expression was assessed in different pathological types of lung Cancer, and it was correlated with other clinicopathologic parameters and patient prognosis. RESULTS: We found a significant association between HHLA2 expression and metastasis. About 83% of patients presented with metastasis showed positive expression of HHLA2 compared to 44.4% in patients with no metastasis (p=0.02). Also, results show significant mild positive correlation between expression of HHLA2 and EGFR markers (p=0.045). The mean OS time in cases with positive HHLA2 expression was nearly half that of patients with negative expression of the markers. However, this difference was not statistically significant. But, PFS of patients was significantly lower among the group with positive expression of HHLA2 compared to the group with negative expression of HHLA2 (p= 0.01). CONCLUSIONS: This study reports that recently discovered, HHLA2 is over expressed in lung cancer associating with higher stage. It is also correlated with EGFR overexpression. HHLA2 could serve as a predictor of progression and distant metastasis. Also, it has potential to be effective immune target in lung cancer immunotherapy such as checkpoint blockade and antibody-drug conjugate treatment.
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