Evaluation of ARK5 and SIRT3 expression in renal cell carcinoma and their clinical significance.

BACKGROUND: Globally Renal Cell Carcinoma (RCC) represents 3% of malignant tumours in adults and 1.78% in Egypt. AMPK-related protein kinase 5 (ARK5) is mainly associated with a hypoxic microenvironment which is a feature of the major RCC subtypes. Additionally, it displays decreased mitochondrial respiration. SIRT3 is a mitochondrial deacetylase that modifies multiple mitochondrial proteins. MATERIAL AND METHODS: Fifty eight cases of RCC, and 30 non-neoplastic cases (of End-Stage Kidney Disease (ESKD) were subjected to immunohistochemistry by ARK5 and SIRT3. The results of IHC were correlated together and correlated with the available clinicopathologic and survival data. RESULTS: Although no significant difference was detected between RCC and ESKD groups regarding ARK5 expression, there was a significant association with RCC regarding H-score and nucleocytoplasmic expression (both P = 0.001). Also, SIRT3 was highly expressed in RCC in comparison to the ESKD group (H-score: P = 0.001). There were significant associations between nucleocytoplasmic ARK5 expression and higher tumour grade, low apoptotic and high mitotic indices, tumour extent, advanced tumour stage, and impaired response of tumours to chemotherapeutic drugs (P = 0.039, P = 0.001, P = 0.027, P = 0.011, P = 0.009, and P = 0.014 respectively). Moreover, the H score of ARK5 expression showed significant associations with tumour grade, apoptotic and mitotic indices, tumour extension, tumour stage, and response to therapy (P = 0.01, 0.035, 0.001, 0.004. 0.003 and 0.013). Regarding SIRT3 expression, it showed significant associations with apoptotic and mitotic indices, tumour extent, tumour stage and response to therapy (P = 0.022, 0.02, 0.042, 0.039 and 0.027). Interestingly, there was a highly significant correlation between the expression of ARK5 and SIRT3 (P = 0.009). Univariate survival analysis revealed a significant association between short survival duration and both nucleocytoplasmic expression of ARK5 and positive SIRT3 expression (P = 0.014 and 0.035). CONCLUSION: ARK5 and SIRT3 are overexpressed in RCC and associated with parameters of poor prognosis as well as short survival. Both seem to influence response to therapy in RCC. So, they could be new targets for therapy that may improve tumour response and patients' survival. There is a postulated relationship that needs more extensive investigation.

Can ß-catenin, Tenascin and Fascin be potential biomarkers for personalized therapy in Gastric carcinoma?

Gastric carcinoma (GC) is one of the most prevalent cancers worldwide and the fourth leading cause of cancer-related death. Studying the molecular profile of GC is essential for developing targeted therapies. ß-catenin, Tenascin, and Fascin expression are among the molecular abnormalities that are claimed to cause GC progression and chemoresistance. Therefore, they could be used as potential therapeutic targets. This study aimed to evaluate ß-catenin, Tenascin, and Fascin expression and their possible roles as prognostic and predictive biomarkers in GC using immunohistochemistry. This retrospective study included 84 GC cases. Tissue microarrays were constructed, followed by ß-catenin, Tenascin, and Fascin immunostaining. Their expression was assessed and compared with clinicopathological parameters and survival data. The study results revealed that ß-catenin nucleocytoplasmic expression, positive Tenascin, and Fascin expressions were detected in 86.9%, 70%, and 59.5% of cases, respectively. Their expression was significantly associated with poor prognostic parameters, such as deeper tumor invasion, lymph node metastasis, advanced pathological stage, vascular invasion, positive omental nodules, poor response to chemotherapy, and short overall survival. Hence, nucleocytoplasmic ß-catenin expression together with Tenascin and Fascin positivity can be potential prognostic and predictive markers, and they can be used as therapeutic targets for GC.

Mutation-Agnostic Detection of Colorectal Cancer Using Liquid Biopsy-Based Methylation-Specific Signatures.

Detection of methylation patterns in circulating tumor DNA (ctDNA) can offer a novel approach for cancer diagnostics given the unique signature for each tumor type. We developed a next-generation sequencing (NGS)-based assay targeting 32 CpG sites to detect colorectal cancer-specific ctDNA. NGS was performed on bisulfite-converted libraries and status dichotomization was done using median methylation ratios at all targets. We included plasma samples from patients with metastatic colorectal (n = 20) and non-colorectal cancers (n = 8); and healthy volunteers (n = 4). Median methylation ratio was higher in colorectal cancer compared with non-colorectal cancers (P = .001) and normal donors (P = .005). The assay detected ctDNA in 85% of patients with colorectal cancer at a specificity of 92%. Notably, we were able to detect methylated ctDNA in 75% of patients in whom ctDNA was not detected by other methods. Detection of methylated ctDNA was associated with shorter median progression-free survival compared to non-detection (8 weeks versus 54 weeks; P = .027).

Plasma fibrinogen level as possible prognostic biomarker in diffuse large B-cell lymphoma.

OBJECTIVES: Although many studies have assessed numerous molecular and immunohistochemical prognostic markers for diffuse large Bcell lymphoma (DLBCL), there is always a need for simple widely available markers. This study was planned to illustrate the clinical significance of baseline plasma fibrinogen levels in DLBCL patients. METHODS: We prospectively investigated 76 DLBCL patients treated with rituximab plus cyclophosphamide, vincristine, doxorubicin and hostacortine between August 2015 and February 2018. Baseline plasma fibrinogen level was measured and correlated with patients' clinical features, laboratory parameters, response to therapy, progression-free survival and overall survival. RESULTS: Significant association between fibrinogen level and clinical features such as the presence of B symptoms (P < .001) and clinical stage (P < .001) was observed while no association with age, gender, number of involved extranodal sites, performance status and international prognostic index (IPI) was found. Baseline fibrinogen level was significantly related to laboratory parameters including red cell distribution width (RDW) (P < .001), platelet count (P = .02), serum lactate dehydrogenase (LDH) (P = .009) and B2-microglobulin (P = .008). No statistically significant correlations were detected between baseline fibrinogen levels; and response to therapy, progression-free survival and overall survival. CONCLUSION: Baseline plasma fibrinogen level did not show prognostic significance for DLBCL patients, although it was associated with patients' clinical features and laboratory parameters. Being simple, cheap and widely available laboratory test, its use should be encouraged routinely in clinical practice to precisely clarify its predictive merit.