Clinicopathological features of CD5-positive splenic marginal zone lymphoma.

AIMS: To investigate the clinicopathological features, immunophenotypes and differential diagnosis of CD5-positive splenic marginal zone lymphoma (SMZL). METHODS: We retrospectively analysed 16 CD5-positive cases of SMZL. Assess their clinicopathological features and survival outcomes to evaluate their similarities and differences with a control group of 25 CD5-negative cases of SMZL. RESULTS: Compared with CD5-negative patients, CD5-positive SMZL tends to be more prone to B symptoms, peripheral lymphadenopathy and extranodal infiltration, high Ann Arbor stage, high International Prognostic Index scores, high serum lactic dehydrogenase and high rates of bone marrow involvement. The 5-year survival rate was significantly shorter than that of the CD5-negative group (52.1% and 81.8%, respectively). CONCLUSIONS: There are many similarities between CD5-positive SMZL and classical CD5-negative SMZL in clinical presentations, morphology and immunohistochemistry, but the former may have a more aggressive clinical course with a poorer prognosis.

Association Between Prognostic Nutritional Index and Prognosis in Patients With Heart Failure: A Meta-Analysis.

Background: The prognostic nutritional index (PNI) has been proposed as a marker of malnutrition and associated with the prognosis of cardiovascular disease. However, whether PNI can serve as a potential biomarker for the prognosis of heart failure (HF) upon those established risk factors were still controversial. This meta-analysis aimed to generate comprehensive evidence on the prognostic value of PNI in patients with HF. Methods: Multiple databases (PubMed, Embase, the Cochrane Library, and Google Scholar) were searched for related studies up to January 31, 2022. Observational studies accessed associations between PNI levels and the prognosis in patients with HF were included for meta-analysis. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. Results: Fourteen studies, comprising 19,605 patients with HF were included for meta-analysis. The median follow-up duration was 18.5 months. Compared with those with higher PNI (normal nutritional status), patients with HF with lower PNI (malnourished) were associated with a higher risk of all-cause mortality (HR 1.53, 95% CI 1.27-1.85) and composite major adverse cardiac outcomes (MACEs; HR 2.26, 95% CI 1.54-3.31) in the multivariable-adjusted model. Furthermore, when PNI was defined as per 1 increment as a continuous metric, higher PNI was associated with a decrease in all-cause mortality (per 1 increment of PNI: HR 0.94, 95% CI 0.88-0.96) and MACEs (per 1 increment of PNI: HR 0.97, 95% CI 0.95-0.98). Conclusions: The PNI can serve as an easily calculated bedside "malnutrition-inflammation" biomarker in HF. Lower PNI was associated with a worse prognosis in patients with HF.

A retrospective study on the clinicopathological and molecular features of 22 cases of natural killer/T-cell lymphoma in children and adolescents.

Natural killer/T-cell lymphoma (NKTCL) in children and adolescents is a rare type of T/NK cell neoplasms. The aim of the present study was to analyze the clinicopathological and genetic features of this rare entity of lymphoma. We evaluated the clinical, histopathological and molecular features of 22 young people with NKTCL, including 15 males and 7 females, with a median age of 15 years. The results revealed that the nasal site was the most involved region while non-nasal sites were observed in 27.3% out of all cases. The tumor cells were composed of small­sized to large cells and 19 (86.4%) cases exhibited coagulative necrosis. The neoplastic cells in all patients were positive for CD3 and the cytotoxic markers. Nineteen (86.4%) cases were positive for CD56. Reduced expression of CD5 was observed in all available cases. CD30 was heterogeneously expressed in 15 (75.0%) cases. All 22 patients were EBV positive. Seven (36.8%) out of all the 19 patients during the follow-up died of the disease, and the median follow­up period was 44 months. Moreover, patients treated with radiotherapy/chemotherapy showed significantly inferior OS compared with the untreated patients. High mutation frequencies were detected including KMT2C (5/5), MST1 (5/5), HLA-A (3/5) and BCL11A (3/5), which involved in modifications, tumor suppression and immune surveillance. These results suggest that NKTCL in children and adolescents exhibits histopathological and immunohistochemical features similar to the cases in adults. Active treatment is necessary after the diagnosis of NKTCL is confirmed. Furthermore, genetic analyse may provide a deep understanding of this rare disease.

GNAQ T96S mutation abrogates the ability of wild-type GNAQ to induce apoptosis by phosphorylating annexin A2 in natural killer/T cell lymphoma.

Our previous study identified annexin A2 (ANXA2) as a Gaq-interacting partner in natural killer/T cell lymphoma (NKTCL) cells transfected with the GNAQ T96S mutation vector by immunoprecipitation and mass spectrometry; however, the detailed molecular mechanisms by which GNAQ T96S might regulate ANXA2 remain to be defined in NKTCL. Herein, we found that the GNAQ T96S mutation significantly promotes the phosphorylation of ANXA2 at the Y24 site, whereas phosphorylation of ANXA2 abolishes the ability of WT GNAQ to trigger cell apoptosis. Further investigation revealed that a GNAQ T96S peptide inhibitor induced apoptosis by competing with ANXA2 binding to GNAQ T96S in NKTCL cells. In vivo animal experiments showed that a GNAQ T96S peptide inhibitor suppresses the growth of NKTCL cells carrying the GNAQ T96S mutation. Our current data suggest a role for GNAQ T96S/Src/ANXA2 in mediating the apoptosis of NKTCL cells, and the GNAQ T96S peptide could be a promising agent for therapy in NKTCL patients.

Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340.

BACKGROUND: Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown. METHODS: qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells. RESULTS: Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1. CONCLUSIONS: Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.

MiR-452 promotes an aggressive colorectal cancer phenotype by regulating a Wnt/ß-catenin positive feedback loop.

BACKGROUND: Aberrant activation of Wnt/ß-catenin signaling pathway is considered to be an important issue in progression and metastasis of various human cancers, especially in colorectal cancer (CRC). MiR-452 could activate of Wnt/ß-catenin signaling. But the mechanism remains unclear. METHODS: The expression of miR-452 in CRC and normal tissues was detected by real-time quantitative PCR. The effect of miR-452 on CRC growth and invasion was conducted by functional experiments in vitro and in vivo. Bioinformatics and cell luciferase function studies verified the direct regulation of miR-452 on the 3'-UTR of the GSK3ß, which leads to the activation of Wnt/ß-catenin signaling. RESULTS: MiR-452 was upregulated in CRC compared with normal tissues and was correlated with clinical significance. The luciferase reporter system studies affirmed the direct regulation of miR-452 on the 3'-UTR of the GSK3ß, which activate the Wnt/ß-catenin signaling. The ectopic upregulation of miR-452 significantly inhibited the expression of GSK3ß and enhanced CRC proliferation and invasion in vitro and in vivo. Meanwhile, knockdown of miR-452 significantly recovered the expression of GSK3ß and attenuated Wnt/ß-catenin-mediated cell metastasis and proliferation. More important, T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors, which are crucial downstream molecules of the Wnt/ß-catenin signaling pathway was verified as a valid transcription factor of miR-452's promoter. CONCLUSIONS: Our findings first demonstrate that miR-452-GSK3ß-LEF1/TCF4 positive feedback loop induce CRC proliferation and migration.