SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer

Colorectal cancer (CRC) is the second most lethal malignancy around the world. Limited efficacy of immunotherapy creates an urgent need for development of novel treatment targets. Secretogranin II (SCG2) is a member of the chromogranin family of acidic secretory proteins, has a role in tumor microenvironment (TME) of lung adenocarcinoma and bladder cancer. Besides, SCG2 is a stroma-related gene in CRC, its potential function in regulating tumor immune infiltration of CRC needs to be fully elucidated. In this study, we used western blot, real-time PCR, immunofluorescence and public databases to evaluate SCG2 expression levels and distribution. Survival analysis and functional enrichment analysis were performed. We examined TME and tumor infiltrating immune cells using ESTIMATE and CIBERSORT algorithm. The results showed that SCG2 expression was significantly decreased in CRC tumor tissues, and differentially distributed between tumor and adjacent normal tissues. SCG2 was an independent prognostic predictor in CRC. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate multiple tumor- and immune-related pathways in CRC, influence tumor immunity by regulating infiltration of immune cells and macrophage polarization in CRC.

Prognostic Impact of lncRNA MCM3AP-AS1 Expression in Malignant Solid Tumors: A Systematic Review and Meta-analysis

Objectives: MCM3AP-AS1 is a newly discovered long non-coding RNA that functions as a biomarker in many different cancer types. However, the pooled role of lncRNA MCM3AP-AS1 in the prognosis of human cancers remains unclear. We performed a systematic review and meta-analysis to explore its potential prognosis for malignant tumors. Materials and methods: A literature survey was conducted by searching in the PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang databases for studies published as of September 1, 2021. The pooled hazard ratio (HR) and 95% confidence interval (95% CI) were calculated to evaluate the relationship between MCM3AP-AS1 expression and overall survival (OS). The endpoints also included various clinical parameters. Results: A total of 14 studies containing 921 cancer patients were finally included into this meta-analysis. The results comprehensively showed that increased MCM3AP-AS1 expression was significantly correlated with poor overall survival (HR = 1.83, 95% CI: 1.56-2.14, P<0.00001). A subgroup meta-analysis for overall survival was conducted. Additionally, high level of lncRNA MCM3AP-AS1 was significantly associated with worse differentiation (OR = 1.76, 95 % CI: 1.12–2.75, P = 0.01), larger tumor size (OR = 2.70, 95 % CI: 1.13–6.46, P = 0.03), advanced clinical stage (OR = 2.52, 95 % CI: 1.32–4.81, P = 0.005) and lymph node metastasis (OR = 2.85, 95 % CI: 1.16–7.00, P = 0.02), respectively. Conclusions: LncRNA MCM3AP-AS1 might be a potential and unfavorable prognostic biomarker of cancer.

Malignant Extracranial Germ Cell Tumours: A First Report by the South African Children’s Cancer Study Group

OBJECTIVE To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol.METHODS A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy proven MEGCTs from birth up to and including 16 years of age. RESULTS Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (HR 0.284 p=0.037) and higher socio-economic status (SES) (HR 0.071; p=0.039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I -96%; stage II - 94.3%; stage III -75.5%; (p=0.017) and stage IV (60.1%; p<0.001). There was a significant association between earlier stage at presentation and higher SES (p=0.03). Patients with a serum AFP level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p=0.002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p<0.001). CONCLUSIONS The cohort demonstrated a 5-year OS of 80.3% with an EFS of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide.

Interleukin-6 Differential Expression in Cancer Patients of Different Clinical Stages; a Possible Biomarker of Cancer Progression

PurposeThe study investigated interleukin-6 expression pattern across all stages of cancer. The research questions raised in the study were: Is there differential expression of Interleukin-6 across all cancer stages? and what relationship exists between serum interleukin-6 level and cancer stage?Methods The prospective case-control study comprised sixty two (62) purposively selected cancer participants across all stages and age range 18 years to 72years as well equal number of healthy volunteers from two medical centres in Nigeria. Three milliliters (3mls) of blood samples was collected intravenously from the participants and centrifuged after 30 minutes of collection at 3000rpm for 10 minutes to obtain serum. The serum level of Interleukin-6 was determined spectrophotometrically by Enzyme linked immunosorbent assay (ELISA). Data obtained were expressed as mean and standard error of the mean. One way Analysis of variance and t-test were employed to test for significance difference between the groups and the significant level was considered at P< 0.05. ResultsFindings from the study revealed significant (P< 0.05) higher mean serum interleukin-6 levels in stage IV cancer participants as compared to other disease stages. In the same way, significant higher mean Interleukin-6 level of stage III cancer participants as compared to that of stage I cancer participants was observed. Furthermore, the study revealed a significant correlation (P< 0.01) between serum Interleukin 6 concentration and cancer stage.Conclusion Serum interleukin-6 had differential expression in cancer patients at advanced clinical stage as compared to that of early disease stage.

Predictive factors of lymph node metastasis and pattern of repartition in patients with epithelial ovarian cancer

Aim: To determine the rate, repartition and risk factors of lymph node (LN) metastasis in patients with epithelial ovarian cancer. Methods: We reviewed retrospectively the pathological and clinical data of 184 patients with epithelial ovarian cancer at a tertiary care center in Beirut, Lebanon. Results: 88% of patients received a pelvic and para-aortic lymphadenectomy. 70% of patients presented LN metastases at both pelvic and para-aortic levels, while isolated pelvic or para-aortic LN metastases were seen in 16 and 14% of cases, respectively. In a univariate analysis, the rate of positive LNs was higher in patients with serous histology (65 vs 33%; p < 0.001), high-grade tumors (68 vs 26%; p < 0.001), bilateral adnexal involvement (74 vs 27%; p < 0.001), advanced clinical stage (p < 0.001), interval debulking surgery (63.2 vs 36.8%; p = 0.003) and positive peritoneal cytology (79 vs 26%; p < 0.001). In a multivariate analysis, the rate of LN involvement was significantly higher in patients with higher grade, advanced clinical stage and positive peritoneal cytology. Conclusion: Serous histology, grade 3 tumors, positive peritoneal cytology, advanced clinical stage, interval surgery and bilateral adnexal involvement can predict LN metastasis in patients with epithelial ovarian cancer.

Clinicopathologic and prognostic implications of Golgi Phosphoprotein 3 in colorectal cancer: A meta-analysis

Background Golgi Phosphoprotein 3 (GOLPH3) has been implicated in the development of colorectal cancer (CRC). Nevertheless, the clinicopathological and prognostic roles of GOLPH3 in CRC remain undefined. We thus did a meta-analysis to assess GOLPH3 association with the clinicopathological characteristics of patients and evaluate the prognostic significance of GOLPH3 in CRC. Methods An electronic search for relevant articles was conducted in the PubMed, Cochrane Library, Web of Science, Medline, Embase, CNKI, and WanFang databases. Two independent reviewers searched all the literature and finished the data extraction and quality assessment. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were used to assess estimates. Stata software (version12.0) was employed to analyze the data. Results A total of 8 published studies were eligible (N = 723 participants). Meta-analysis revealed that GOLPH3 was found to be highly expressed in tumor tissues compared to that of adjacent colorectal tissues (OR, 2.63), and overexpression of GOLPH3 had significant relationship with advanced clinical stage (OR, 3.42). GOLPH3 expression was not correlated with gender (OR, 0.89), age (OR, 0.95), positive lymphatic metastasis (OR, 1.27), tumor size (OR, 1.12), poor differentiation of tumor (OR, 0.56) or T stage (OR, 0.70). Moreover, GOLPH3 overexpression was not associated with worse overall survival (OS) (HR = 1.14, 95% CI: 0.42–1.86, P>0.05) and disease-free survival (DFS) (HR = 0.80, 95% CI:-0.26–1.86, P>0.05). Conclusions GOLPH3 overexpression is correlated with tumor stage, which is an adverse clinicopathological characteristic of CRC. But, GOLPH3 can not serve as a useful biomarker in evaluating the progression of CRC.

FISH-Guided Evaluation of Hyperdiploidy and Other Cytogenetic Abnormalities in Childhood Burkitt Lymphoma

Background: Burkitt lymphoma (BL) is the most common lymphoma in childhood. Apart from MYC rearrangement, considered the hallmark of the disease, BL often presents with additional chromosome aberrations, the biological and clinical significance of which is not fully understood. Materials and methods: The study included 72 children (55 boys, 17 girls), aged 2-16 years (median 9), with BL diagnosed on the basis of histopathology and a demonstrable MYC rearrangement. Touch imprints from the diagnostic biopsy samples were investigated with i-FISH for MYC, BCL2, BCL6, IGH, IGK and IGL rearrangements genes and copy number aberrations involving 1q21/1p32, 7cen/7q31, 9cen/9p21, 13q14/13q34 and 17cen/17p13. Deviations from the diploid status were further investigated for aneusomies of the carrier chromosome with the use of appropriate chromosome enumeration probes. Results: MYC gene was demonstrated in all cases with MYC/IGH fusion in 83.3% (60/72). 47 cases (65.3%) were found with least one additional aberration, most commonly with 1q gain (29.2%), 7q gain (19.4%), 13q deletion (19.4%), hemizygous 9p loss (8.3%) and hyperdiploidy (8.3%). Advanced clinical stage (IV), 7q gain (but not trisomy 7) and -9/9p- were significantly associated with shorter overall survival. There was no instance of relapse or death among the hyperdiploid cases. Conclusions: This extensive FISH investigation on imprints of affected tissue provides clinically meaningful information on the genetic profile of BL and may prove valuable in the management of patients with no karyotype available. In particular, the demonstration of hyperdiploidy through the use of chromosome enumeration probes could offer the means for the delineation of clonal evolution pathways and the recognition of a subgroup of children with excellent prognosis who could be cured with low-intensity chemotherapy regimens. Disclosures Kattamis: VIFOR: Consultancy; CRISPR/Vertex: Consultancy, Honoraria; Agios Pharmaceuticals: Consultancy; IONIS: Consultancy; BMS/Celgene: Consultancy, Honoraria, Research Funding; Chiesi: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy.

Vasohibin-1 expression as a biomarker of aggressive nature in ductal adenocarcinoma of the prostate: a retrospective cohort study at two centres in Japan

ObjectivesVasohibin-1 (VASH1) is an endogenous angiogenesis regulator expressed in activated vascular endothelial cells. We previously reported that high VASH1 expression is a predictor of progression in acinar adenocarcinoma of the prostate. In this study, we evaluated the characteristics of ductal adenocarcinoma of the prostate by comparing the level of VASH1 expression between ductal and acinar adenocarcinoma specimens.Design and settingA retrospective cohort study at two centres in Japan.ParticipantsAmong the 1495 patients who underwent radical prostatectomy or transurethral resection for the past 15 years, a total of 14 patients diagnosed with ductal adenocarcinoma and 20 patients diagnosed with acinar adenocarcinoma with a Gleason score of 4+4 were included.InterventionsWe immunohistochemically examined the CD34 expression as the microvessel density (MVD) and activated endothelial cells as the VASH1 density (vessels per mm2).Primary and secondary outcome measuresThe primary outcome was the association of MVD and VASH1 density between ductal and acinar adenocarcinoma, and the secondary outcome was their oncological outcomes.ResultsNine patients (64.3%) with ductal adenocarcinoma were diagnosed at an advanced clinical stage, and five patients (35.7%) died from cancer during a median follow-up of 56.0 months. The VASH1 densities (mean±SD) in ductal and acinar adenocarcinoma were 45.1±18.5 vs 16.1±21.0 (p<0.001), respectively, while the MVD (mean±SD) in ductal and acinar adenocarcinoma were 65.3±21.9 vs 80.8±60.7 (p=0.666), respectively. The 5-year cancer-specific survival rates for high and low VASH1 expression were 70.0% and 100.0% (p=0.006), respectively. High VASH1 expression and a diagnosis of ductal adenocarcinoma were significant predictors of cancer-specific survival.ConclusionsDuctal adenocarcinoma was more aggressive and had higher VASH1 expression than acinar adenocarcinoma, although MVD was equivalent. These results indicate that VASH1 expression may serve as a novel biomarker for the aggressive nature of ductal adenocarcinoma.

INFLUENCE OF RENAL DYSFUNCTION ON THE LEVEL OF SERUM ANGIOPOIETIN-LIKE PROTEINS AND ANTI-PHOSPHOLIPID ANTIBODIES IN PATIENTS WITH RHEUMATOID ARTHRITIS AND METABOLIC SYNDROME

Rheumatoid arthritis (RA) is a frequent background for the development of renal pathology. Chronic kidney disease (CKD) is determined in more than 30% of patients with RA. Along with inflammation and other factors in the progression of the underlying disease, the development of renal damage in RA is facilitated by the presence of metabolic syndrome (MetS).The aim of this study is to assess the relationship of serum concentrations of angiopoietin-like proteins (ANGPTL) and antiphospholipid antibodies (aPL) with the development of renal dysfunction in patients with RA.We examined 158 patients with RA (91.8% – women and 8.2% – men) aged 21 to 80 years old and an average duration of the disease – 9 (4-15) years. The majority of patients were seropositive for rheumatoid factor and for antibodies to cyclic citrullinated peptide, with an advanced clinical stage and moderate activity (3.2 < DAS28 ≤ 5.1) of the pathological process.The ELISA test was used for the quantitative determination of angiopoietin-like protein type 3 and type 4 and antibodies to phospholipids (aРL-IgG/IgM) for total detection of antibodies to cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylic acid and a complex of negatively charged phospholipid and β2-glycoprotein-I.More than half of the examined RA patients had the calculated glomerular filtration rate (eGFR) ranging from 89 to 60 ml/min/1.73 m2 (allocation by CKD stages: C1 – 21.5%; C2 – 58.9%; C3 – 19.6%). Signs of MetS (a combination of increased blood pressure, increased triglyceride levels and carbohydrate metabolism disorders against the background of central obesity) were diagnosed in 68 (43%) RA patients. Multivariable analysis of variance was performed to compare the studied parameters (ANGPTL3, ANGPTL4, aPL) depending on eGFR in groups of RA patients without signs of metabolic syndrome and RA patients with MetS. Significant differences in the level of ANGPTL3 (F = 8.86, p = 0.0034) and ANGPTL4 (F = 29.6, p < 0.001), but not aPL (p > 0,05) were found between RA patients with varying degrees of severity of metabolic disorders.Multivariable analysis of variance showed a significant increase in ANGPTL4 in the blood serum of RA patients with reduced eGFR (< 89 ml/min) (F = 18.5, p < 0.001) and pronounced metabolic changes (F = 24.2, p < 0.001). Thus, only two factors (renal dysfunction and the presence of MetS) had a direct effect on the ANGPTL4 content in RA patients, which could describe the variability of this sign in more than 30% of cases. The squared multiple correlation coefficient (R2 ) in this model was 0.33. ANGPTL type 4 should be considered as a key factor linking the development of renal dysfunction and metabolic changes caused by rheumatoid inflammation.

Mesoporous Silica Nanoparticles for Potential Immunotherapy of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide, which lacks effective inhibition of progression and metastasis in the advanced clinical stage. Mesoporous silica nanoparticle (MSN)–based cytotoxic or immunoregulatory drug–loading strategies have attracted widespread attention in the recent years. As a representative of mesoporous biomaterials, MSNs have good biological characteristics and immune activation potential and can cooperate with adjuvants against HCC. This review summarizes the possible future development of the field from the perspective of tumor immunity and aims to stimulate the exploration of the immune mechanism of MSN-based therapy. Through this point of view, we hope to develop new clinical immune drugs that can be applied to HCC clinical management in the future.