Fig 2: Immunostaining of neuroendocrine tumors. Representative photomicrographs demonstrating anti-connective tissue growth factor (CCN2) (panel A) immunostaining of gut carcinoid tumor tissue. CCN2 immunoreactivity was seen in cells corresponding to chromogranin A-positive tumor cells and gut smooth muscle (denoted by arrows in panels B and C, respectively). All sections were counterstained with hematoxylin. Magnification ×50.

Fig 3: Linear relationship between plasma connective tissue growth factor and right ventricular strain. Scatter plot showing the inverse relationship between plasma connective tissue growth factor (CCN2) levels and right ventricular strain (linear regression, r = 0.47, p < 0.001). Due to the presence of extreme outliers, plasma CCN2 levels are plotted on the y-axis using a logarithmic (log10) scale.

Fig 4: Relationship between plasma connective tissue growth factor and degree of valvular regurgitation. Box plot displaying the relationship between plasma connective tissue growth factor (CCN2) levels and the degree of tricuspid and/or pulmonary regurgitation. Median, interquartile range, and maximum and minimum values are shown. Due to the presence of extreme outliers, plasma CCN2 levels are plotted on the y-axis using a logarithmic (log10) scale. The highest plasma CCN2 levels were seen in the patients with moderate to severe right-sided valvular regurgitation (Kruskal-Wallis test, p = 0.03).

Fig 5: Utility of plasma connective tissue growth factor as a predictor of reduced right ventricular function. Receiver operating characteristic (ROC) curve depicting the ability of plasma connective tissue growth factor (CCN2) levels to predict the presence of reduced right ventricular (RV) function (AUC 0.82 [95% CI 0.72;0.92], p < 0.001). Plasma CCN2 levels = 77 µg/L had 88% sensitivity and 69% specificity for detecting patients with reduced RV function.