Inflammation-scores as prognostic markers of overall survival in lung cancer: a register-based study of 6,210 Danish lung cancer patients

Background Inflammation-scores based on general inflammation markers are suggested as prognostic markers of overall survival (OS) in lung cancer. However, whether these inflammation-scores improves the prognostication performed by well-established prognostic markers is unsettled. In a large register-based lung cancer patient cohort, nine different inflammation-scores were compared, and their ability to optimize the prognostication of OS was evaluated. Methods Lung cancer patients diagnosed from 2009–2018 in The Central Denmark Region were identified in the Danish Lung Cancer Registry. Pre-treatment inflammation markers were extracted from the clinical laboratory information system. Prognostication of OS was evaluated by Cox proportional hazard models. Comparison of the inflammation-scores and their added value to established prognostic markers were assessed by Akaike's information criteria and Harrel's C-index. Results In total, 5,320 patients with non-small cell lung cancer (NSCLC) and 890 patients with small cell lung cancer (SCLC) were identified. In NSCLC, the Aarhus composite biomarker score (ACBS), including albumin, C-reactive protein, neutrophil count, lymphocyte count and haemoglobin, and the neutrophil-lymphocyte-ratio (NLR) were superior. Furthermore, they improved the prognostication of OS significantly (p <0.0001) (ACBS: HR: 2.24 (95%CI: 1.97–2.54); NLR: HR: 1.58 (95%CI: 1.47 – 1.69)). In SCLC, three scores were equally superior and improved the prognostication of OS p < 0.0001): neutrophil–lymphocyte-ratio (HR:1.62 (95%CI: 1.38–1.90)), modified Glasgow Prognostic Score (mGPS) (HR:1.70 (95%CI: 1.55–1.86) and the Combined NLR and GPS (CNG) (HR:2.10 (95%CI: 1.77–2.49). Conclusions The ACBS was the optimal score in NSCLC, whereas neutrophil–lymphocyte-ratio, mGPS and CNG were equally superior in SCLC. Additionally, these inflammation-scores all optimised the prognostication of OS and added value to well-established prognostic markers.

Landscape Analysis of Matrix Metalloproteinases Unveils Key Prognostic Markers for Patients With Breast Cancer

Breast cancer (BRCA) is the most common cancer in the world, of which incidence rate and mortality are the highest in women. Being responsible for the remodeling and degradation of extracellular matrix proteins, matrix metalloproteinases (MMPs) have been regarded as one of the most important protease family related to tumorigenesis. It has been demonstrated that MMPs play crucial roles in some tumor invasion and metastasis. However, the potential roles of MMPs in tumorigenesis and progression of BRCA and its subtype remain elusive. Herein, we conducted a systematic study on MMPs via a series of database-based retrospective analysis, including TCGA, R Studio, GEPIA, Kaplan-Meier Plotter, cBioPortal, STRING, GeneMANIA and TIMER. As a result, many MMP family members were differentially expressed in patients with BRCA, e.g., the expressions of MMP1, MMP9, MMP11 and MMP13 were up-regulated, whereas the expression levels of MMP19 and MMP28 were down-regulated. MMP9, MMP12, MMP15 and MMP27 were significantly correlated with the clinical stages of BRCA, implying their important roles in the occurrence and development of BRCA. In addition, the survival analysis indicated that different expression pattern of MMPs exhibited distinct outcomes in patient with BRCA, e.g., patients with high expression of MMP2, MMP8, MMP16, MMP17, MMP19, MMP20, MMP21, MMP24, MMP25, MMP26 and MMP27 had a prolonged survival time, while the others (MMP1, MMP7, MMP9, MMP12 and MMP15) exhibited poor prognosis. Subsequent functional and network analysis revealed MMPs were mainly correlated with parathyroid hormone synthesis and secretion pathway, collagen metabolism, and their effect on the activities of serine hydrolase, serine peptidase and aminopeptidase. Notably, our analysis showed that the expression of MMPs was significantly correlated with the infiltration of various immune cells in BRCA, including CD8+T cells, CD4+T cells, macrophages, neutrophils, B cells, and dendritic cells, suggesting the close correlations between MMPs and immune functions. In short, our study disclosed MMPs play multiple biological roles in the development of BRCA, MMP1 and MMP9 might be used as independent prognostic markers and potential therapeutic targets for diagnosis and treatment for patients with BRCA.

Prognostic Value of Intratumoral Collagen Quantification in Canine Oral Melanomas

The majority of the melanocytic neoplasms are considered malignant and highly metastatic. However, a subset of the melanocytic tumors has a more favorable prognosis and the identification of precise prognostic markers for this neoplasm may be useful to guide treatment. The collagen architecture and density have been shown to correlate with tumor progression in human breast cancer and canine mast cell tumors. The purpose of the present study was to investigate the prognostic value of the intratumoral collagen index (ICI) as an indicator of postsurgical survival and its relation with other prognostic markers for canine oral melanomas (OMs). Twenty-two cases were tested for intratumoral collagen density using Masson's trichrome stain and morphometry. No differences were found between dogs regarding survival. The ICI was not correlated with proliferative activity or nuclear atypia. The results presented herein indicate that the quantity of intratumoral collagen in canine OMs is not an efficient indicator of postsurgical survival. Complementary studies about the expression and activity of enzymes that are capable of degrading extracellular matrix (ECM) components are necessary.

Gene expression profiles of some prognostic markers in a human breast cell line (MCF7) exposed to Curcumin nanoparticles and nanocapsules

Introduction: Worldwide, cancer is a significant public health problem. Curcumin exhibits anti-inflammatory, antiproliferative, and anticancer properties when used in medicine. Investigated study for Curcumin's chemopreventive mechanism against human malignancies, this research examined the cellular and molecular alterations generated by curcumin modified compound in breast cancer (MCF-7) cell lines. Oncogenic EGFR and VEGFR2 mutations lead to the formation, invasion, and maintenance of malignant phenotypes in humans, including breast cancer. Studied prognostic markers such as C-myc and Ki67 in breast cancer, and the apoptotic gene as Caspase-3 have been done. Aim of the work: The purpose of this study is to determine the therapeutic efficacy of curcumin nanoparticles and nanocapsules in breast cancer cell lines (MCF7). Materials and methods: We used real-time PCR to assess the expression of the C-myc, Ki67, EGFR, VEGFR2, and Caspase-3 genes in MCF7 cells treated with Curcumin nanoparticles and nanocapsules. Results: Curcumin nanoparticles and nanocapsules boosted apoptotic cell populations considerably regardless of the nanotechnology used. Additionally, the mRNA expression analysis results indicated that the mechanism activated by curcumin nanocapsules involved the upregulation of the oncogenes EGFR and VEGFR2. In comparison to curcumin nanoparticles, curcumin nanocapsules significantly reduced the expression of Ki67 and c-myc mRNAs in breast cancer cells. The mRNA expression study revealed that curcumin nanocapsules produce an increase in the apoptotic Caspase-3 gene production compared to cells treated with curcumin nanoparticles. Conclusion: This work demonstrates that curcumin nanoparticles created using a novel mechanical process can be employed successfully as an anticancer agent. These findings add to our understanding of the molecular mechanisms behind curcumin nanocapsules' anticancer activity in breast cancer.

VISTA, PDL-L1, and BRAF—A Review of New and Old Markers in the Prognosis of Melanoma

Melanoma is currently known as one of the most aggressive malignant tumors. The prognostic factors and particularities of this neoplasm are a persistent hot topic in the medical field. This review has multiple purposes. First, we aim to summarize the known data regarding the histological and immunohistochemical appearance of this versatile tumor and to look further into the analysis of several widely used prognostic markers, such as B-Raf proto-oncogene, serine/threonine kinase BRAF. The second purpose is to analyze the data on the new prognostic markers, V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) and Programmed death-ligand 1 (PD-L1). VISTA is a novel target that is considered to be highly important in determining the invasive potential and treatment response of a melanoma, and there are currently only a limited number of studies describing its role. PD-L1 is a marker with whose importance has been revealed in multiple types of malignancies, but its exact role regarding melanoma remains under investigation. In conclusion, the gathered data highlights the importance of correlations between these markers toward providing patients with a better outcome.

IMMUNE CYTOPENIAS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (PECULIARITIES, PROGNOSTIC MARKERS)

Background: Immune cytopenia (IC) is one of the major complications in chronic lymphocytic leukemia (CLL). The paper describes the peculiarities of different immune cytopenia in CLL patients and the importance of individual prognostic markers in the course of the disease. Methods: We observed 62 patients with CLL complicated by immune cytopenia. Among these patients 30 had autoimmune hemolytic anemia (AIHA), 18 experienced immune thrombocytopenia (ITP), 10 had Fisher-Evans syndrome (FES), 3 were diagnosed with partial red cell aplasia (PRCA), and immune neutropenia (IN) was revealed in 1 patient. In addition to general examination and laboratory studies, the following examinations were performed: immunophenotyping of peripheral blood lymphocytes, flow cytometry (CD5; CD19; CD20; CD23; CD38; ZAP70), Coombs test, a molecular cytogenetic study of peripheral blood lymphocytes using the FISH method with TP53 and ATM probes, the level of ß2-microglobulin. Results: It was established that the overall survival of CLL patients with IC depends on the form of the latter. The median overall survival in patients with Fisher-Evans syndrome was the shortest (75 months), slightly better survival was observed in patients with AIHA (median 80 months), the best survival was found in patients with ITP (median not reached). Among unfavorable markers of CLL with IC, there is the presence of del 11q22.3. Unfavorable prognostic markers were also the following: a positive Coombs test, high levels of ZAP 70 expression, and high levels of ß2-microglobulin