Genes and Cancer最新文献

The CEA family comprises 18 genes and 11 pseudogenes located at chromosome 19q13.2 and is divided into two main groups: cell surface anchored CEA-related cell adhesion molecules (CEACAMs) and the secreted pregnancy-specific glycoproteins (PSGs). CEACAMs are highly glycosylated cell surface anchored, intracellular, and intercellular signaling molecules with diverse functions, from cell differentiation and transformation to modulating immune responses associated with infection, inflammation, and cancer. In this review, we explore current knowledge surrounding CEACAM1, CEACAM5, and CEACAM6, highlight their pathological significance in the areas of cancer biology, immunology, and inflammatory disease, and describe the utility of murine models in exploring questions related to these proteins.

The t (8; 21) (q22; q22) with the resulting RUNX1- RUNX1T1 rearrangement is one of the most common cytogenetic abnormalities in acute myeloid leukemia (AML). It is associated with favorable prognosis. The t (5; 17) (q35; q21) is an uncommon translocation, fuses the gene for the nucleophosmin (NPM) to the retinoic acid receptor α(RARA) and was described essentially in acute promyelocytic leukemia (APL) variant. We present the case of a 19-year-old male patient who developed an AML with t (8; 21) (q22; q22) associated to t (5; 17) (q35; 21). Morphology and immunophenotype of the leukemic cells were compatible with AML. The patient received chemotherapy based on cytarabine and anthracycline without all-trans retinoic acid (ATRA) followed by allogenic stem cell transplantation in first remission. To the best of our knowledge, this is the first report of an association between a rare translocation t (5; 17) and t (8; 21) in AML. In this report, we will discuss the prognosis of this association as well as the treatment.

Tumor-associated inflammation and chromosomal aberrations can play crucial roles in cancer development and progression. In neuroblastoma (NB), the enzyme cyclooxygenase-2 (COX-2) is associated with copy number alterations on the long arm of chromosome 11 (Ch 11q), defining an aggressive disease subset. This retrospective study included formalin-fixed paraffin-embedded tumor samples collected from nine patients during diagnosis at the pediatric Pequeno Principe Hospital, Curitiba, PR, Brazil, and post-chemotherapy (CT). COX-2 expression was evaluated using immunohistochemistry and correlated with the genome profile of paired pre- and post-CT samples, determined by array comparative genomic hybridization. A systems biology approach elucidated the PTGS2 network interaction. The results showed positive correlations between pre-CT Ch 7q gain and COX-2 expression (ρ = 0.825; p-value = 0.006) and negative correlations between Ch 7q gain and Ch 11q deletion (ρ = -0.919; p-value = 0.0005). Three samples showed Ch 11q deletion and Ch 7q gain. Network analysis identified a direct connection between CAV-1 (Ch 7q) and COX-2 in NB tumors and highlighted the connection between amplified genes in Ch 7q and deleted ones in 11q. The identification of hub-bottleneck-switch genes provides new biological insights into this connection between NB, tumorigenesis, and inflammation.

Aim: Cervical cancer (CC) is one of the most common cancers in women. Recent advances in screening and vaccination against the papilloma virus (HPV) have increased protection against CC. However, there is no effective diagnostic biomarker and treatment approach during the course of the disease. The current study is thus aimed to evaluate the changes in the expression of lncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA MVIH) and its diagnostic value as a biomarker in CC patients.

Materials and methods: One-hundred and fifteen (n = 115) pairs of CC primary tumor and marginal non-tumor tissue samples were obtained from Tabriz Valiasr International Hospital (Tabriz, Iran). RNA extraction and cDNA synthesis followed by quantitative reverse transcriptase PCR (qRT-PCR) were considered to investigate alterations in the expression levels of MVIH in patients with CC. The associations between MVIH expression changes and clinicopathological features as well as its potential as a diagnostic biomarker were assessed using SPSS and GraphPad prism software and the receiver operating characteristic (ROC).

Results: The expression levels of MVIH were significantly higher in CC tumors as compared to marginal non-tumor samples (p < 0.0001). Overexpression of MVIH was significantly associated with younger age (p = 0.033), lymph node metastasis (p = 0.031), tumor invasion depth (p = 0.035), and squamous cell type of CC (p = 0.019). The ROC analysis for MVIH as a diagnostic biomarker revealed the respective sensitivity and specificity of 67.83 and 80.

Conclusions: Overexpression of MVIH in CC tumors suggests its oncogenic role during tumorigenesis. Thus, it may serve as a potential diagnostic biomarker.

Hepatocellular carcinoma (HCC) is the primary form of liver cancer and a major cause of cancer death worldwide. Early detection is key to effective treatment. Yet, early diagnosis is challenging, especially in patients with cirrhosis, who are at high risk of developing HCC. Dysfunction or loss of function of the transforming growth factor β (TGF-β) pathway is associated with HCC. Here, using quantitative immunohistochemistry analysis of samples from a multi-institutional repository, we evaluated if differences in TGF-β receptor abundance were present in tissue from patients with only cirrhosis compared with those with HCC in the context of cirrhosis. We determined that TGFBR2, not TGFBR1, was significantly reduced in HCC tissue compared with cirrhotic tissue. We developed an artificial intelligence (AI)-based process that correctly identified cirrhotic and HCC tissue and confirmed the significant reduction in TGFBR2 in HCC tissue compared with cirrhotic tissue. Thus, we propose that a reduction in TGFBR2 abundance represents a useful biomarker for detecting HCC in the context of cirrhosis and that incorporating this biomarker into an AI-based automated imaging pipeline could reduce variability in diagnosing HCC from biopsy tissue.

Background: Chronic infection with Helicobacter pylori is one of the main causes of gastric cancer (GC). Besides, lncRNAs play crucial roles in cancer pathobiology including GC. Here we aimed to investigate the expression of MEG3 and HOTAIR in gastric cancer tissues and evaluate their association with the H. pylori status.

Materials and methods: One hundred samples were obtained. Total RNA was extracted, cDNA was synthesized and expression of MEG3 and HOTAIR was assessed using qRT-PCR. Association of their expression with H. pylori status and other clinicopathological characteristics were investigated. Furthermore, sensitivity and specificity of the MEG3 and HOTAIR expression levels for discrimination of the tumor and non-tumor samples were evaluated by Receiver operating characteristic (ROC) curve analysis.

Results: We observed upregulation of HOTAIR but downregulation of MEG3 in tumor compared to the non-tumor tissues. We also found a significant negative association between their expression levels and H. pylori positive status. However, only the expression level of HOTAIR was significantly associated with the size and stage of the tumor (P < 0.05). The ROC curve analysis revealed that the expression levels of MEG3 and HOTAIR might discriminate GC tumor and non-tumor tissues.

Conclusions: In conclusion, this study revealed a negative association between H. pylori infection and expression of MEG3 and HOTAIR. The results suggested that the expression level of these lncRNAs might be considered as potential biomarkers for GC.

The cell cycle is regulated in part by cyclins and their associated serine/threonine cyclin-dependent kinases, or CDKs. CDK4, in conjunction with the D-type cyclins, mediates progression through the G₁ phase when the cell prepares to initiate DNA synthesis. Although Cdk4-null mutant mice are viable and cell proliferation is not significantly affected in vitro due to compensatory roles played by other CDKs, this gene plays a key role in mammalian development and cancer. This review discusses the role that CDK4 plays in cell cycle control, normal development and tumorigenesis as well as the current status and utility of approved small molecule CDK4/6 inhibitors that are currently being used as cancer therapeutics.

Ewing sarcoma is a cancer of bone and soft tissue in children driven by EWS::ETS fusion, most commonly EWS::FLI1. Because current cytotoxic chemotherapies are not improving the survival of those with metastatic or recurrent Ewing sarcoma cases, there is a need for novel and more effective targeted therapies. While EWS::FLI1 is the major driver of Ewing sarcoma, EWS::FLI1 has been difficult to target. A promising alternative approach is to identify and target the molecular vulnerabilities created by EWS::FLI1. Here we report that EWS::FLI1 induces the expression of Slit2, the ligand of Roundabout (Robo) receptors implicated in axon guidance and multiple other developmental processes. EWS::FLI1 binds to the Slit2 gene promoter and stimulates the expression of Slit2. Slit2 inactivates cdc42 and stabilizes the BAF chromatin remodeling complexes, enhancing EWS::FLI1 transcriptional output. Silencing of Slit2 strongly inhibited anchorage-dependent and anchorage-independent growth of Ewing sarcoma cells. Silencing of Slit2 receptors, Robo1 and Robo2, inhibited Ewing sarcoma growth as well. These results uncover a new role for Slit2 signaling in stimulating Ewing sarcoma growth and suggest that this pathway can be targeted therapeutically.