Serum growth differentiation factor 15 as a biomarker for malnutrition in patients with acute exacerbation of chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that often coexists with malnutrition during acute exacerbation (AECOPD) and significantly affects the prognosis. Previous studies have shown that growth differentiation factor 15 (GDF15) levels promote appetite suppression, weight loss, and muscle weakness, and are markedly high in peripheral blood following inflammatory stimulation. However, it is still unknown whether serum GDF15 levels can be used to predict malnutrition in patients with AECOPD. Methods: A total of 142 patients admitted to the Department of Respiratory Medicine at Anshun People's Hospital between December 2022 and August 2023 were selected for this study. The participants were divided into two groups: malnutrition group (n = 44) and non-malnutrition group (n = 98) based on a body mass index (BMI) < 18.5 kg/m2, according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. Serum GDF15 levels were measured using the enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Spearman correlation analysis was used to examine the association between serum GDF15 levels, baseline data, and clinical indicators. Binary logistic regression was used to identify the independent risk factors for AECOPD combined with malnutrition. The predictive value of serum GDF15, albumin (ALB), and a combination of these was evaluated to identify malnutrition in patients with AECOPD using a receiver operating characteristic (ROC) curve. Results: Serum GDF15 levels in patients with malnutrition and AECOPD were significantly higher than those in patients without malnutrition, whereas the serum ALB levels were significantly lower than those in patients without malnutrition (p < 0.001). Moreover, serum GDF15 levels were negatively correlated with BMI (r = -0.562, p < 0.001), mid-arm circumference (r = -0.505, p < 0.001), calf circumference (r = -0.490, p < 0.001), total protein (r = -0.486, p < 0.001), ALB (r = -0.445, p < 0.001), and prognostic nutritional index (r = -0.276, p = 0.001), and positively correlated with C-reactive protein (r = 0.318, p < 0.001), COPD assessment test score (r = 0.286, p = 0.001), modified medical research council classification (r = 0.310, p < 0.001), and global initiative for chronic obstructive pulmonary disease grade (r = 0.177, p = 0.035). Furthermore, serum GDF15 levels were an independent risk factor for malnutrition in patients with AECOPD (OR = 1.010, 95% CI, 1.003∼1.016). The optimal cut-off value of serum GDF15 level was 1,092.885 pg/mL, with a sensitivity of 65.90% and a specificity of 89.80%, while the serum ALB level was 36.15 g/L, with a sensitivity of 86.40% and a specificity of 65.00%, as well as a combined sensitivity of 84.10% and a specificity of 73.90%. Serum GDF15 and serum ALB levels had a good predictive ability (AUC = 0.856, AUC = 0.887), and the ROC revealed a greater combined prediction value for the two (AUC = 0.935). Conclusion: Serum GDF15 levels could be used as a potential biomarker in the prediction of malnutrition in patients with AECOPD, offering a guidance for future clinical evaluation of malnutrition.

[Relationship between epithelial-mesenchymal transition and basal cell-like phenotype in breast cancer].

OBJECTIVES: To evaluate the relationship between epithelial-mesenchymal transition and basal cell-like phenotype breast cancer (BLBC). METHODS: Three hundred and eighty two cases of breast cancers including basal cell-like, luminal A, luminal B and Her-2 subtypes were collected from 458 cases of invasive breast cancers based on their immunophenotypes. They were then stained immunohistochemically with FOXC-2, vimentin, Syndecan-1 and E-cadherin. The relationship of these markers with the basal cell-like phenotype of breast cancer was studied. RESULTS: Of the 41 BLBC cases, FOXC-2, vimentin and Syndecan-1 were positive in 14 cases (34.1%), 18 cases (43.9%) and 36 cases (87.7%) respectively; E-cadherin expression was reduced in 26 cases (63.4%). The positive rates of FOXC-2 and vimentin were higher in BLBC than in other subtypes of breast cancer (P < 0.01). The expression of E-cadherin was the lowest among the 4 subtypes of breast cancers (P < 0.01). Syndecan-1 was positive in the stromal cells adjacent to cancer cells in 17 cases (41.5%) BLBC and the expression was higher than that in other subtypes (P = 0.007). There existed a correlation between FOXC-2 and vimentin expression in BLBC (r = 0.607, P < 0.01). The rates of positive lymph nodes in FOXC-2 and vimentin positive BLBC cases were 71.4% and 66.7% respectively, and both were higher than those of FOXC-2 and vimentin negative BLBC cases (P = 0.002 and P = 0.001). CONCLUSION: Epithelial-mesenchymal transition is probably related to the basal cell-like phenotype of breast cancers, and this may be one of the reasons accounting for the different biological behavior of BLBC from other subtypes of breast cancer.

[Clinicopathologic characteristics of breast cancer with basal-like immunophenotype].

OBJECTIVE: To study the clinicopathologic characteristics of basal-like immunophenotype breast cancer (BLBC). METHODS: 458 cases of female infiltrative breast cancer were studied using immunohistochemical staining with an antibody panel of ER, PR, HER2, Ki-67, CK5/6, CK14 and epidermal growth factor receptor (EGFR) and were classified basing on the immunophenotypes. The clinicopathologic characteristics were compared with other immunophenotypes of breast cancer. 228 of 458 cases of breast cancer were followed up. RESULTS: 46 cases of BLBC were screened out among the 458 breast cancers. And histological features of BLBC were analysed including the larger diameter of cancer foci (average 3.3 cm), appearance of squeezing phenomenon of neighboring cell borders (58.7%, 27/46), geography-like distribution of necrosis (52.2%, 24/46), central zone fibrosis (30.4%, 14/46) and lymphoplasmacytic infiltration at the margin and stroma (63.0%, 29/46). There were nuclear pleomorphism with numerous mitoses. The cancer cells were closely arranged, forming irregular solid architectures. There was a high expression (> 25%) of Ki-67 (43.5%, 20/46). CK5/6, CK14 and EGFR were positive in 58.7% (27/46), 43.5% (20/46) and 65.2% (30/46) respectively. 3-year survival rate of BLBC was 66.9%, lower than the luminal A breast cancer and similar to HER2 over-expression breast cancer. CONCLUSIONS: The proportion of BLBC in the group of breast cancers is 10%. BLBC has its distinct histological and cytological features. Currently, it is still necessary to depend on immunophenotyping in making a BLBC diagnosis. BLBC is the one of breast cancer subtypes with the poorest prognosis.