Screening for the Key Proteins Associated with Rete Testis Invasion in Clinical Stage I Seminoma via Label-Free Quantitative Mass Spectrometry

Rete testis invasion (RTI) is an unfavourable prognostic factor for the risk of relapse in clinical stage I (CS I) seminoma patients. Notably, no evidence of difference in the proteome of RTI-positive vs. -negative CS I seminomas has been reported yet. Here, a quantitative proteomic approach was used to investigate RTI-associated proteins. 64 proteins were differentially expressed in RTI-positive compared to -negative CS I seminomas. Of them, 14-3-3γ, ezrin, filamin A, Parkinsonism-associated deglycase 7 (PARK7), vimentin and vinculin, were validated in CS I seminoma patient cohort. As shown by multivariate analysis controlling for clinical confounders, PARK7 and filamin A expression lowered the risk of RTI, while 14-3-3γ expression increased it. Therefore, we suggest that in real clinical biopsy specimens, the expression level of these proteins may reflect prognosis in CS I seminoma patients.

BCR activated CLL B cells use both CR3 (CD11b/CD18) and CR4 (CD11c/CD18) for adhesion while CR4 has a dominant role in migration towards SDF-1

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the western world. In previous studies, various proportion of patients was found to carry CD11b+ or CD11c+ B cells whose presence was an unfavourable prognostic factor. The exact mechanism however, how these receptors contribute to the pathogenesis of CLL has not been revealed so far. Here we analysed the role of CD11b and CD11c on B cells of CLL patients in the adhesion to fibrinogen and in the migration towards stromal cell derived factor-1 (SDF-1) and studied the role of CR4 in the adherence of the CD11c+ B cell line BJAB. We observed that both CR3 and CR4 mediate adhesion of the malignant B cells. Moreover, we found, that CR4 was strongly involved in the migration of the leukemic cells towards the chemoattractant SDF-1. Our data suggest that CR3 and CR4 are not only passive markers on CLL B cells, but they might contribute to the progression of the disease. Since the role of SDF-1 is prominent in the migration of CLL cells into the bone marrow where their survival is supported, our findings help to understand how the presence of CD11c on leukemic B cells can worsen the prognosis of chronic lymphocytic leukaemia.

Primary tumour ulceration in cutaneous melanoma: its role on TNM stages.

Background Tumour ulceration has unfavourable prognostic factor in stage I–II melanoma. The aim of this study was to question whether tumour ulceration might predict relapse and survival in melanomas of all stages. Methods A total of 911 melanoma patients were analysed. Results The 5-year relapse-free survival rates were 50.0% for ulcerated melanomas and 75.8% for all non-ulcerated melanomas (P = 0.0001). Ulcerated melanomas had lower relapse-free survival rates than non-ulcerated melanomas in all T-stages (P = 0.0001). The relapse-free survival rates were statistically significant for T1 (P = 0.02), T3 (P = 0.01) and T4 (P = 0.004); however, T2 (P = 0.07). There were significant differences between ulcerated melanomas and non-ulcerated melanomas regarding relapse-free survival rates for both N0 (P = 0.0001) and N1 (P = 0.01) patients; poor relapse-free survival rates were found to be in association with ulcerated melanomas (P = 0.06 for N1, P = 0.04 for N2 and P = 0.8 for N3 disease). The 5- year overall survival rates were 55.3 and 81.5% for ulcerated melanomas and non-ulcerated melanomas, respectively (P = 0.0001). Ulcerated melanomas had lower overall survival rates than non-ulcerated melanomas in all T-stages; they were statistically significant for T1 (P = 0.01), T2 (P = 0.03) and T4 (P = 0.006), but not for T3 (P = 0.3). Ulceration predicted poor survival in N0 patients; however, it was not found significant although its overall survival rate was lower in node-positive patients (P = 0.09), and ulceration was a significantly poor prognostic factor only for N3 patients (P = 0.03), but not for N1 (P = 0.9) and N2 patients (P = 0.2). Furthermore, non-metastatic patients with ulcerated melanomas survived significantly less (P = 0.0001), but there were no differences in survivals between ulcerated melanoma and non-ulcerated melanoma metastatic melanoma patients (P = 0.1). Conclusion Primary tumour ulceration has been considered as a poor prognostic factor in local melanomas, but it might also have a potential for predicting survival in loco-regional and advanced melanomas.

Correction: Long non-coding RNA SNHG17 is an unfavourable prognostic factor and promotes cell proliferation by epigenetically silencing P57 in colorectal cancer

Correction for ‘Long non-coding RNA SNHG17 is an unfavourable prognostic factor and promotes cell proliferation by epigenetically silencing P57 in colorectal cancer’ by Zhonghua Ma et al., Mol. BioSyst., 2017, 13, 2350–2361.

Long non-coding RNA SNHG17 is an unfavourable prognostic factor and promotes cell proliferation by epigenetically silencing P57 in colorectal cancer

The first report of potential mechanisms of IncRNA SNHG17 in CRC, prompting the development of IncRNA-directed diagnosis and treatments.

Hyponatremia – unfavourable prognostic factor in hepatic cirrhosis

Hyponatremia is defined by a level of Na in serum below or equal to 136 mEq/L while in hepatic cirrhosis it is classically considered as relevant only at a level of Na below 130 mEq/L. Hyponatremia frequently occurs in patients with end-stage hepatic disease. The frequency and severity are variable but it has been estimated that it occurs with a frequency of 57% in hospitalized patients with cirrhosis and in those on waiting lists for hepatic transplants. Signs and symptoms of hyponatremia are related to dysfunctions of the central nervous system, due to migration of the water from intravascular space to the brain cells, resulting in the occurrence of cerebral edema. Therapeutic options in hyponatremia are limited and are based on restriction of water consumption, exclusion of diuretics and vaptans. Hepatic transplant remains the only definitive treatment for end-stage hepatic diseases in which hyponatremia has occurred.