Our previous study found that zinc finger protein 71 (ZNF71) mRNA expression was associated with chemosensitivity and its protein expression was prognostic of non-small-cell lung cancer (NSCLC). The Krüppel associated box (KRAB) transcriptional repression domain is commonly present in human zinc finger proteins, which are linked to imprinting, silencing of repetitive elements, proliferation, apoptosis, and cancer. This study revealed that ZNF71 KRAB had a significantly higher expression than the ZNF71 KRAB-less isoform in NSCLC tumors (n = 197) and cell lines (n = 117). Patients with higher ZNF71 KRAB expression had a significantly worse survival outcome than patients with lower ZNF71 KRAB expression (log-rank p = 0.04; hazard ratio (HR): 1.686 [1.026, 2.771]), whereas ZNF71 overall and KRAB-less expression levels were not prognostic in the same patient cohort. ZNF71 KRAB expression was associated with epithelial-to-mesenchymal transition (EMT) in both patient tumors and cell lines. ZNF71 KRAB was overexpressed in NSCLC cell lines resistant to docetaxel and paclitaxel treatment compared to chemo-sensitive cell lines, consistent with its association with poor prognosis in patients. Therefore, ZNF71 KRAB isoform is a more effective prognostic factor than ZNF71 overall and KRAB-less expression for NSCLC. Functional analysis using CRISPR-Cas9 and RNA interference (RNAi) screening data indicated that a knockdown/knockout of ZNF71 did not significantly affect NSCLC cell proliferation in vitro.
PURPOSE The combination of anatomical and biological factors of breast cancer in a new staging system has a prognostic role. This study investigates the prognostic value of the Bioscore among patients with breast cancer with respect to disease-free survival (DFS). MATERIAL AND METHODS This study included 317 patients with breast cancer who were identified between January 2015 and December 2018 at Clinical Oncology Department of Assiut University Hospital. Their cancer baseline characteristics were recorded: pathologic stage (PS), T stage (T), nodal stage (N), grade (G), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status. Univariate and two multivariate analyses were performed to identify which of these variables are associated with DFS. Model performance was quantified using Harrell's concordance index (C-index), and the Akaike information criterion (AIC) was used to compare model fits. RESULTS The significant factors in the univariate analysis were PS3, T2, T3, T4, N3, G2, G3, ER-negative, PR-negative, and HER2-negative. In the first multivariate analysis, PS3, G3, and ER-negative were the significant factors, and in the second multivariate analysis, T2, T4, N3, G3, and ER-negative were the significant factors. Two sets of models were built to determine the utility of combining variables. Models incorporating G and ER status had the highest C-index (0.72) for T + N + G + ER in comparison with (0.69) PS + G + ER and the lowest AIC (953.01) for T + N + G + ER and (966.9) for PS + G + ER. Conclusion Using the Bioscore in breast cancer staging helps to identify patients at increased risk of recurrence. It provides more optimistic prognostic stratification than the anatomical staging alone for DFS.
552 Background: Serum vitamin D levels have been linked to breast cancer development; however, the impact on breast cancer features and outcomes remains unclear. The present study aimed at investigating the prognostic value of baseline vitamin D level among non-metastatic breast cancer patients. Methods: In this study; we prospectively assessed female patients presenting to our department with non-metastatic breast cancer during the period from October 2018 to December 2019 for their baseline serum vitamin D levels measured by ELISA test before starting systemic therapy, in addition to other clinicopathological factors. Low Vit-D was defined as Vit-D level less than 30 ng /l. Chi-square test (Fisher’s exact test) was used to examine the relation between qualitative variables. Survival analysis was done using Kaplan-Meier method and comparison between two survival curves was done using log-rank test. Multivariate analysis was done using Cox-regression hazard model for the significant factors affecting survival on univariate analysis. Results: We enrolled 221 patients with non-metastatic breast cancer as they matched our eligibility criteria. Median age at diagnosis was (50.7± 10.9). About two thirds of the patients (64.7%) were post menopause. Median vitamin D level was (23.1 ng/l) with a range of (4-62.46 ng/liter). Around half of the patients (56.5%) had vitamin D level lower than 30 ng/liter, with higher numbers of low vitamin D levels among HER2 positive and triple negative (TNBC) patients compared to hormonal receptor positive (HR+ve) patients (P=<0.001). There was a significant negative correlation between vitamin D levels and tumor size, lymph node positivity and stage at diagnosis (the lower the vitamin D level, the larger the tumor size, and the higher the number of positive lymph nodes and the stage; r= -0.414, r= -0.586, r= -0.674; respectively; p<0.001). On follow up, the number of local recurrences, bone metastases and liver metastases were significantly higher among the low vitamin D level group, however; there was no significant difference between the two groups in terms of development of brain and lung metastases. Disease free survival (DFS) and overall survival (OS) was significantly worse among the low vitamin D level group (p<0.001). Conclusions: Low serum vitamin D in breast cancer patients negatively correlates with tumor size, lymph node positivity and stage at diagnosis. It is linked to HER-2 positive and TNBC, and is significantly associated with worse DFS and OS.
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