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[This corrects the article DOI: 10.1371/journal.pone.0239803.].

Studies carried out in the last decade have demonstrated that the members of the KCTD protein family play active roles in carcinogenesis. Very recently, it has been reported that KCTD15, a protein typically associated with other physio-pathological processes, is involved in medulloblastoma and leukemia. Starting with some preliminary indications that emerged from the analysis of online databases that suggested a possible overexpression of KCTD15 in breast cancer, in this study, we evaluated the expression levels of the protein in breast cancer cell lines and in patients and the effects of its silencing in the HER2+ cell model. The analysis of the KCTD15 levels indicates a significant overexpression of the protein in Luminal A and Luminal B breast cancer patients as well as in the related cell lines. The greatest level of over-expression of the protein was found in HER2+ patients and in the related SKBR3 cell line model system. The effects of KCTD15 silencing in terms of cell proliferation, cell cycle, and sensitivity to doxorubicin were evaluated in the SKBR3 cell line. Notably, the KCTD15 silencing in SKBR3 cells by CRISPR/CAS9 technology significantly attenuates their proliferation and cell cycle progression. Finally, we demonstrated that KCT15 silencing also sensitized SKBR3 cells to the cytotoxic agent doxorubicin, suggesting a possible role of the protein in anti HER2+ therapeutic strategies. Our results highlight a new possible player in HER2 breast cancer carcinogenesis, paving the way for its use in breast cancer diagnosis and therapy.

Evidence suggests a beneficial role of the Mediterranean Diet (MedDiet) on health-related quality of life (HRQoL) in healthy subjects. HRQoL is relevant in cancer therapy and disease outcomes, therefore we investigated the association between adherence to the MedDiet and HRQoL in breast cancer survivors participating in the multicentre trial DEDiCa. Diet and HRQoL were assessed at baseline in a subgroup of 309 women enrolled within 12 months of breast cancer diagnosis without metastasis (stages I-III, mean age 52±1 yrs, BMI 27±7 kg/m2). The 14-item PREDIMED questionnaire was used to analyse adherence to the MedDiet. HRQoL was assessed with three validated questionnaires measuring physical, mental, emotional and social factors: EQ-5D-3L, EORTC QLQ-C30 and EORTC QLQ-BR23. Analysis of variance (ANOVA) and multivariate analyses were performed to assess the possible role of the MedDiet on HRQoL. Patients with higher adherence to MedDiet (PREDIMED score >7) showed significantly higher scores for physical functioning (p = 0.02) and lower scores on the symptomatic pain scale (p = 0.04) assessed by the EORTC QLQ-C30 questionnaire compared to patients with a lower adherence to MedDiet (PREDIMED score ≤7). Higher scores from the EQ-5D-3L indicating higher well-being were observed mainly in participants with higher MedDiet adherence (p = 0.05). In adjusted multivariate analyses significant positive associations were found between MedDiet, physical functioning (p = 0.001) and EQ 5D-3L score (p = 0.003) while inverse associations were found with pain and insomnia symptoms (p = 0.005 and p = 0.029, respectively). These results suggest that higher adherence to the MedDiet in breast cancer survivors is associated with better aspects of quality of life, specifically higher physical functioning, better sleep, lower pain and generally higher well-being confirming findings in healthy subjects.