Evaluation of the correlation of vasculogenic mimicry, ALDH1, KAI1 and microvessel density in the prediction of metastasis and prognosis in colorectal carcinoma

Abstract

Background: Metastasis and recurrence are the most common reasons for treatment failure of colorectal carcinoma (CRC). Vasculogenic mimicry (VM, blood supply formation often seen in highly aggressive tumors), Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse human cancers. However, the correlation of VM, ALDH1, KAI1 and microvessel density (MVD) in CRC is unclear. In this study, we analyzed the correlations among VM, ALDH1, KAI1 and MVD, as well as their respective correlations with clinicopathological parameters and survival in CRC.

Methods: The level of VM, ALDH1, KAI1 and MVD in 204 whole tissue samples of CRC were examined by immunhistochemistry. Clinical data was also collected.

Results: Levels of VM, ALDH1 and MVD were significantly higher, and levels of KAI1 significantly lower, in CRC tissues than in normal colorectal tissues. Levels of VM, ALDH1 and MVD were positively associated with invasion of depth, lymph node metastasis (LNM), distant metastasis and tumor-node-metastasis (TNM) stages, and negatively with patients' overall survival (OS). Levels of KAI1 was negatively correlated with invasion of depth, LNM, distant metastasis and TNM stages, and the KAI1 positive expression subgroup had significantly longer OS than did the KAI1- subgroup. In multivariate analysis, high levels of VM, ALDH1 and KAI1, as well as TNM stages were independently correlated with lower OS in patients with CRC.

Conclusions: VM, MVD and the expression of ALDH1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets for CRC.

Keywords: ALDH1; CRC; KAI1; MVD; Prognosis; VM.

Fig. 1

Immunostaining of ALDH1, or VM or KAI1 in CRC or the control tissue. a Negative staining ALDH1 in the control tissue (400 magnification); b Positive staining of ALDH1 in the cytoplasm of cancer cells (400 magnification); c Positive staining of VM in the colorectal carcinoma tissues (100 magnification, white arrow is VM structure, black arrow is microvessel); d Positive staining of VM in the colorectal carcinoma tissues (400 magnification, white arrow is VM structure); e Positive staining of KAI1 in the membrane of control tissues (400 magnification); f Negative staining of KAI1 in the colorectal carcinoma tissues (100 magnification, Fig. b, c, d, f are serial sections)

Fig. 2

Kaplan-Meier analysis of the survival rate of patients with colorectal carcinoma. a Overall survival of all patients in relation to ALDH1 expression (log-rank = 16.908, P < 0.001); b Overall survival of all patients in relation to VM (log-rank = 86.416, P < 0.001); c Overall survival of all patients in relation to MVD (log-rank = 15.610, P < 0.001); d Overall survival of all patients in relation to KAI1 expression (log-rank = 60.613, P < 0.001). In a, b, c and d analyses, the green line represents positive staining of factors (MVD score ≥21 is positive) and the blue line represents negative staining factors (MVD score <21 is negative). e Overall survival of all patients in relation to the combination of KAI1, ALDH1, VM and MVD (log-rank = 97.184, P < 0.001). The green line represents positive expression of KAI1 and negative expression of ALDH1, VM and MVD and the blue line represents negative expression of KAI1 and positive expression of ALDH1, VM and MVD. The red line represents other positive or negative expression of the proteins