In this issue of EBioMedicine Enroth and colleagues present

In this issue of EBioMedicine, Enroth and colleagues () present a comprehensive study that analyzes the individual contribution of factors related to the collection and long-term sample storage in a highly homogenous group of Northern European subjects (). Taking advantage of the sampling strategy of the Västerbotten Intervention and Mammography screening programs in northern Sweden () at the Umeå Biobank, this study intended to disentangle the effects of freezer storage time and individual age in a relatively homogenous cohort of subjects. The study analyzed the levels of 108 proteins, as assessed by the highly specific multiplex assays which use antibody-mediated proximity paired oligonucleotides and PCR amplification (). They selected 380 periodically-drawn specimens from 106 healthy local females with ages of 40, 50 and 60years from 1988 through 2014 from the Västerbotten Intervention Program and from the Mammography Screening Program for females in the 50 to 69 age group since 1995. All female specimens were collected at specific ages in a concrete population with relatively small purchase RG2833 level. In a nutshell, this study provides evidence that in addition to the storage time, which affected 18 proteins and explained 4.8–34.9% of the observed variance, the chronological age at sample collection, and to a lesser degree, the season of collection were responsible for part of the variance. In fact, the chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance, very similar to the effect of storage time, while the seasonal variation in specimens collected in a region with a large variation in daylight hours between winter and summer, affected 15 proteins and explained up to 4.6% of the variance seen in protein abundance levels after adjustment for storage-time and age. This finding is also interesting since the town of Umea in Sweden is located at 63 degrees North and receives an average of 60 daylight hours per month during the winter months (November to March) compared to over 260hours per month during summer (June to August). Skin radiation affects the circulating levels of plasma proteins (), and sunlight hours may viewed as a proxy variable to other seasonal changes such as plant blooming or increasing pollen levels which in turn triggers the immune system, or various forms of changes in lifestyle such as seasonal intakes of food and levels of physical activity. In this manuscript, Enroth and colleagues () present three examples of significant changes in protein levels which were illustrative of this effect (TGFβ1, HSP-27, IL-20RA) where levels were significantly lower during the summer months (except July when no specimens had been collected). While this variation had already been reported for other tests like serum cholesterol (), this study provides additional information on the actual weight of the effect of collection season on potential biomarker analyses and shows that although the season of the year does matter, its weight compared with the storage time and donor chronological time is much lesser.
MiRNAs were originally identified as small non-coding RNAs that control the timing of larval development in (). MiRNAs are short, single stranded RNA molecules that serve as master regulators of gene expression. They have been widely implicated in pathogenesis of several human diseases, including cancers (). Their abnormal levels in tumors have important pathogenetic consequences: miRNAs overexpressed in tumors contribute to oncogenesis by downregulating tumor suppressors. For example, miR17–92 cluster reduces tumorigenic levels of E2F1 transcription factor in lymphomas (), or miR-21 represses PTEN tumor suppressor in hepatocellular carcinomas (). On the other hand, miRNAs lost by malignant cells generally result in oncogene overexpression. For example, let-7 family represses RAS, HMGA2 and MYC in lung cancers (), or miR-15a and miR-16-1 downregulate BCL2 in chronic lymphocytic leukemias and cyclin D1 in prostate cancer and mantle cell lymphoma (). However, several studies have shown that miRNAs\' roles in cancer are tissue and tumor specific: for example, in breast cancer models, miR-200 family has been shown to work as an oncogene and enhance distant metastasis (), whereas in ovarian, renal and lung tumors low expression of miR-200 family members significantly associated with worse overall survival and also inhibited angiogenesis ().