Clinical Performance of Friend Leukemia Virus Integration 1 Methylation as a Biomarker for Colorectal Carcinoma

Objectives Accumulating evidence supports the reliability of molecular biomarkers and cancer, the current situation is lacking. This present study was aimed to investigate clinical performance of friend leukemia virus integration 1 (FLI1) methylation as a biomarker for colorectal cancer (CRC). Methods The datasets of UALCAN, GEPIA, cBioPortal, STRING, TIMER2.0, GEO, and KOBAS were utilized in this present study. In order to testify the methylation function of FLI1 in CRC, we studied 6 CRC cell lines and 20 pairs of tumor tissues. The transcriptional levels of FLI1 were tested by reverse transcription PCR quantitatively and western blot. Cell viability, transwell assays and plate clone assay were utilized to assess the cell function. Results FLI1 was up-regulated in the GBM, KIRC, LAML, etc. Meanwhile, it was down-regulated in BLCA, BRCA, CESC, etc (p<0.05). The CPTAC dataset showed higher total protein in the primary tissues of KIRC, lower protein in the BRCA, OV, LUAD, UCEC than normal tissues(p<0.05). Highly expressed FLI1 was linked to poor prognosis of overall survival (OS) in LGG, UVM (p<0.05). Low expression of FLI1 was associated with short OS in KIRC, LUAD, SKCM (p<0.05). Compared with normal tissues, the methylation level of FLI1 was increased in BRCA, CESC, CHOL, COAD, etc (p<0.05). In the contrary, it was decreased in KIRP, PCPG obviously (p<0.05). Moreover, it showed a reduced phosphorylation for selected probes (BRCA: NP_002008.2:S39, NP_002008.2:S3241; OV: NP_002008.2:S39; LUAD: NP_002008.2:S79, NP_002008.2:S3241; all p<0.05). Meanwhile, it showed an enhanced phosphorylation level of FLI1 in KIRC for selected probes (NP_002008.2:S241, p<0.05). Besides, a statistical negative correlation was found between FLI1 and Treg cells, neutrophils, monocytes, macrophages, NK cells, cancer-associated fibroblasts, and common immune checkpoint gene levels (p<0.05). Besides, in vivo experience showed that 5-Aza-2’-deoxycytidine diminished FLI1 methylation level and restored transcriptional levels (p>0.05) in CRC. In vitro experiments demonstrated that the proliferation, colony formation, invasion and migration of CRC cells were inhibited by FLI1 overexpression through FMNL1 (p<0.05). Conclusions This present study offers a comprehensive understanding of FLI1 in carcinomas with oncogenesis and immunotherapeutic implications. Moreover, FLI1 reduced the proliferation, colony formation, invasion and migration of CRC by FMNL1.

Clinicopathological significance and underlying molecular mechanism of downregulation of basonuclin 1 expression in ovarian carcinoma

In this study, we aim to identify the clinical significance of basonuclin 1 ( BNC1) expression in ovarian carcinoma (OV) and to explore its latent mechanisms. Via integrating in-house tissue microarrays, gene chips, and RNA-sequencing data, we explored the expression and clinical value of BNC1 in OV. Immunohistochemical staining was utilized to confirm the protein expression status of BNC1. A combined SMD of –2.339 (95% CI: –3.649 to –1.028, P < 0.001) identified that BNC1 was downregulated based on 1346 samples, and the sROC (AUC = 0.93) showed a favorable discriminatory ability of BNC1 in OV patients. We used univariate and multivariate Cox regulation to evaluate the prognostic role of BNC1 for OV patients, and a combined hazard ratio of 0.717 (95% CI: 0.445–0.989, P < 0.001) revealed that BNC1 was a protective factor for OV. Furthermore, the fraction of infiltrating naive B cells, memory B cells, and other immune cells showed statistical differences between the high- and low- BNC1 expression groups through cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Enrichment analysis showed that BNC1 may have a relationship with immune-related items in OV. By predicting the potential regulatory transcription factors (TFs) of BNC1, friend leukemia virus integration 1 ( FLI1) may be a potential upstream TF of BNC1. Corporately, a decreasing trend of BNC1 may serve as a tumor suppressor and prognostic biomarker in OV patients. Moreover, BNC1 may take part in immune-related pathways and influence the fraction of tumor-infiltrating immune cells.

Retiform hemangioendothelioma: a rare lesion of the vulva

Retiform hemangioendothelioma (RH) is a rare borderline-malignant vascular tumor with specific histological characteristics, usually occurring in the limbs and trunk. We report the case of a 63-year-old woman who presented with a painless, oval nodule that had been growing slowly on her left vulva for 3 years. Magnetic resonance imaging of the pelvic cavity revealed a 4.4- × 2.7- × 1.8-cm cystic lesion in the subcutaneous fat of the left vulva. Resection beyond the macroscopic border was performed. Pathology revealed vascular structures with elongated and narrow arborizing vascular channels that were arranged in a retiform pattern resembling rete testis tissue. Immunohistochemical endothelial staining was positive for CD31, CD34, and Friend leukemia integration-1 (FLI-1). The above features confirmed a diagnosis of RH. There was no local recurrence or metastasis during the 26-month follow-up. RH of the vulva is rare, and its diagnosis is supported by specific histological characteristics and immunohistochemical staining for CD31, CD34, and FLI-1. Wide surgical resection with tumor-free margins is important for a favorable prognosis.

Successful Radical Pneumonectomy for a Primitive Neuroendodermal Tumor in the Lung: A Case Report and Review of the Literature

Peripheral primitive neuroendodermal tumors (PNETs) and Ewing's sarcoma belong to the Ewing family of tumors and are small round-cell malignancies originating from spinal cord cells. These tumors account for 5% of all small round-cell malignant neoplasms. PNETs that arise from the lung parenchyma without pleural or chest wall involvement are very rare. We report a case of an adult female with a large pulmonary PNET who had given birth just 1 month prior to the diagnosis. She had cough and expectoration for 6 months, and the preoperative examination showed no metastases. Thus, we performed radical pneumonectomy and lymph node dissection. The patient recovered well without surgical complications and was discharged 7 days after the surgery. Postoperative pathology confirmed that the tumor was a small round-cell malignancy, and the tumor cells were positive for CD99, Friend leukemia virus integration 1 (FLI-1), and neuron-specific enolase (NSE), which was consistent with the diagnosis of a PNET. For primary large pulmonary PNETs, radical pneumonectomy may be a safe surgical method, worthy of further application in clinical practice.

Postnatal Growth Restriction in Mice Alters Cardiac Protein Composition and Leads to Functional Impairment in Adulthood

Postnatal growth restriction (PGR) increases the risk for cardiovascular disease (CVD) in adulthood, yet there is minimal mechanistic rationale for the observed pathology. The purpose of this study was to identify proteomic differences in hearts of growth-restricted and unrestricted mice, and propose mechanisms related to impairment in adulthood. Friend leukemia virus B (FVB) mouse dams were fed a control (CON: 20% protein), or low-protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce 20% less milk, inducing growth restriction. At birth (postnatal; PN1), pups born to dams fed the CON diet were switched to LP dams (PGR group) or a different CON dam. At PN21, a sub-cohort of CON (n = 3 males; n = 3 females) and PGR (n = 3 males; n = 3 females) were euthanized and their proteome analyzed by two-dimensional differential in-gel electrophoresis (2D DIGE) and mass spectroscopy. Western blotting and silver nitrate staining confirmed 2D DIGE results. Littermates (CON: n = 4 males and n = 4 females; PGR: n = 4 males and n = 4 females) were weaned to the CON diet. At PN77, echocardiography measured cardiac function. At PN80, hearts were removed for western blotting to determine if differences persisted into adulthood. 2D DIGE and western blot confirmation indicated PGR had reductions in p57kip2, Titin (Ttn), and Collagen (Col). At PN77, PGR had impaired cardiac function as measured by echocardiography. At PN80, western blots of p57kip2 showed protein abundance recovered from PN21. PN80 silver staining of large molecular weight proteins (Ttn and Col) was reduced in PGR. PGR reduces cell cycle activity at PN21, which is recovered in adulthood. However, collagen fiber networks are altered into adulthood.

Do Primitive Neuroectodermal Tumors of the Kidney Have a Predilection for Inferior Vena Cava Involvement? A Case Series and Review of the Literature

The primitive neuroectodermal tumor (PNET) of the kidney is an extremely rare neoplasm, the diagnosis of which mainly depends upon histopathology, immunohistochemistry (IHC), and cytogenetics. A handful of cases reported in the literature mention about aggressive features of this neoplasm. The purpose of our study was to review our experience in not only the diagnosis and management of the patients with renal PNET but also to highlight its propensity to involve inferior vena cava (IVC) and also present a rare occurrence of Ewing’s sarcoma (ES)/PNET of the renal pelvis. The clinical, operative, and histopathology records of four patients of renal PNET treated between January 2017 and December 2019 were reviewed and data analyzed concerning the available literature. Out of the four patients treated, two had level III and IV IVC thrombus, and one had dense desmoplastic adhesions with the IVC wall. One of the cases had a rare presentation of ES/PNET of the renal pelvis. All patients were managed surgically, while only one patient received adjuvant chemotherapy and following up with remission for the last 2 years and 4 months. On IHC, cluster of differentiation-99 (CD-99) was positive in all patients, and three were positive for Friend leukemia integration-1. PNET of the kidney is primarily an immunohistopathological diagnosis. This neoplasm has an increased propensity for the local invasion of surrounding structures. A multimodality approach with surgery, chemotherapy, and radiotherapy could offer better outcomes, although the prognosis of these tumors remains poor.

Do Primitive Neuroectodermal Tumors of the Kidney Have a Predilection for Inferior Vena Cava Involvement?

The primitive neuroectodermal tumor (PNET) of the kidney is an extremely rare neoplasm, the diagnosis of which mainly depends upon his-topathology, immunohistochemistry (IHC), and cytogenetics. A handful of cases reported in the literature mention about aggressive features of this neoplasm. The purpose of our study was to review our experience in not only the diagnosis and management of the patients with renal PNET but also to highlight its propensity to involve inferior vena cava (IVC) and also present a rare occurrence of Ewing’s sarcoma (ES)/PNET of the renal pelvis.The clinical, operative, and histopathology records of four patients of renal PNET treated between January 2017 and December 2019 were reviewed and data analyzed concerning the available literature. Out of the four patients treated, two had level III and IV IVC thrombus, and one had dense desmoplastic adhesions with the IVC wall. One of the cases had a rare presentation of ES/PNET of the renal pelvis. All patients were managed surgically, while only one patient received adjuvant chemotherapy and following up with remission for the last 2 years and 4 months. On IHC, cluster of differentiation-99 (CD-99) was positive in all patients, and three were positive for Friend leukemia integration-1. PNET of the kidney is primarily an immunohistopathological diagnosis. This neoplasm has an increased propensity for the local invasion of surrounding structures. A multimodality approach with surgery, chemotherapy, and radiotherapy could offer better outcomes, although the prognosis of these tumors remains poor.

miR-145a Regulation of Pericyte Dysfunction in a Murine Model of Sepsis

Background Sepsis is a life-threatening systemic disease with severe microvascular dysfunction. Pericytes preserve vascular homeostasis. To our knowledge, the potential roles of microRNAs in sepsis-induced pericyte dysfunction have not been explored. Methods We determined lung pericyte expression of miR-145a in cecal ligation and puncture (CLP)–induced sepsis. Mouse lung pericytes were isolated and transfected with a miR-145a mimic, followed by stimulation with lipopolysaccharide (LPS). We measured inflammatory cytokine levels. To assess the functions of miR-145a in vivo, we generated a pericyte-specific miR-145a–knockout mouse and determined sepsis-induced organ injury, lung and renal vascular leakage, and mouse survival rates. We used RNA sequencing and Western blotting to analyze the signaling pathways regulated by miR-145a. Results CLP led to decreased miR-145a expression in lung pericytes. The miR-145a mimic inhibited LPS-induced increases in cytokines. In CLP-induced sepsis, pericytes lacking miR-145a exhibited increased lung and kidney vascular leakage and reduced survival rates. We found that miR-145a could suppress LPS-induced NF-κB activation. In addition, we confirmed that the transcription factor Friend leukemia virus integration 1 (Fli-1) is a target of miR-145a and that Fli-1 activates NF-κB signaling. Conclusion Our results demonstrated that pericyte miR-145a mediates sepsis-associated microvascular dysfunction, potentially by means of Fli-1–mediated modulation of NF-κB signaling.