Abstract

BackgroundMetastasis 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.MethodsThe level of VM, ALDH1, KAI1 and MVD in 204 whole tissue samples of CRC were examined by immunhistochemistry. Clinical data was also collected.ResultsLevels 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.ConclusionsVM, MVD and the expression of ALDH1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets for CRC.

Highlights

  • Metastasis and recurrence are the most common reasons for treatment failure of colorectal carcinoma (CRC)

  • Correlations between Aldehyde dehydrogenase 1 (ALDH1), vasculogenic mimicry (VM), microvessel density (MVD) or KAI1 and clinicopathological variables To assess the contributions of ALDH1, VM, MVD and KAI1 to CRC, the results thereof were immunohistochemically assessed for both CRC and normal colorectal mucosa tissue samples

  • The positive expression rate of ALDH1 in CRC was positively correlated with tumor invasion, lymph node metastasis, distant metastasis and TNM stage, but not with patients age, gender, tumor size, grade or location (Table 2)

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Summary

Introduction

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. The most common reasons for cancer treatment failure are metastasis and recurrence. This may be related to a small population of tumor cells which named as cancer stem cells (CSC) or tumor initiating cells (TIC). ALDH1 has been considered as a useful marker for metastasis and poor prognosis in various malignant tumors, including pancreatic cancer, esophageal cancer, lung cancer and gastric cancer [11,12,13,14]

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