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Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis.

ABSTRACT: CD105 and its ligand transforming growth factor beta (TGFbeta) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40-9.00) and 3.10 (range 0.90-8.00), respectively. Kaplan-Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFbeta1 and TGFbeta3 together with the receptor-ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFbeta1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFbeta1 level was noted in patients with carcinoma over the controls. Furthermore, TGFbeta3 and CD105/TGFbeta3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFbeta1 was expressed in cancer cells but TGFbeta3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFbeta1, TGFbeta3 and CD105/TGFbeta complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

SUBMITTER: Li C

PROVIDER: S-EPMC2741032 | biostudies-other | 2003 May

REPOSITORIES: biostudies-other

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Project description:BackgroundLactate dehydrogenase (LDH) is associated with the prognosis of many diseases, but the relationship between LDH and the poor prognosis (recurrence and death) of acute ischemic stroke (AIS) has not been fully clarified. This study aimed to investigate the association between admission LDH level and poor prognosis in patients with AIS.MethodsThis retrospective study enrolled AIS patients treated in Taizhou Hospital of Zhejiang Province from July 2019 to December 2019. Poor prognosis included AIS recurrence and all-cause death at 3, 6, and 18 months. The correction between LDH and poor prognosis or all-cause death was assessed. Lasso Cox expression and multivariate Cox expression analyses were used to evaluate the association of LDH with the risk of poor prognosis and all-cause death, respectively. A nomogram was constructed to evaluate the predictive Values of LDH for the poor prognosis and all-cause death of AIS.Results732 patients were included in the study. Multivariate analysis shows that admission LDH levels were significantly correlated with poor prognosis [odds ratio (OR),1.003; 95% confidence interval (95% CI), 1.001-1.005; P = 0.001] and all-cause death (OR, 1.005; 95% CI, 1.000-1.009; P = 0.031). The correlation analysis showed that admission LDH level was positively correlated with National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score. Time-dependent receiver operating characteristic (td-ROC) curves analysis showed that the AUC values of admission LDH level for predicting prognosis of AIS patients in 3-month, 6-month, 12-month and 18-month were 0.706 (95% CI, 0.604-0.810), 0.653 (95% CI, 0.583-0.723), 0.616 (95% CI, 0.556-60676) and 0.610 (95% CI, 0.552-0.680), respectively. And td-ROC also showed that the AUC values of admission LDH level for predicting all-cause death of AIS patients in 3-month, 6-month,12-month and 18-month were 0.861 (95% CI, 0.764-0.958), 0.824 (95% CI, 0.753-0.890), 0.726 (95% CI, 0.633-0.819) and 0.715 (95% CI, 0.622-0.807), respectively. The nomograms were constructed to create the predictive models of the poor prognosis and all-cause death of AIS.ConclusionHigher LDH levels are independently associated with poor prognosis and all-cause death of AIS.

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Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis.

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