Metastasis-associated in colon cancer-1 and aldehyde dehydrogenase 1 are metastatic and prognostic biomarker for non-small cell lung cancer

Abstract

Background: Tumor recurrence and metastasis are the most common reason for treatment failure. Metastasis-associate in colon cancer-1 (MACC1) has been identified as a metastatic and prognostic biomarker for colorectal cancer and other solid tumors. Aldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or ALDH1 in non-small cell lung cancer (NSCLC) is unclear. In this study, we explored the relationship between MACC1 and ALDH1 expression, as well as their respective associations with clinicopathological features, to determine if either could be useful for improvement of survival prognosis in NSCLC.

Methods: The expression levels of both MACC1 and ALDH1 in 240 whole tissue sections of NSCLC were examined by immunohistochemistry. Clinical data were also collected.

Results: MACC1 and ALDH1 were significantly overexpressed in NSCLC tissues when compared to levels in normal lung tissues. Investigation of associations between MACC1 or ALDH1 protein levels with clinicopathological parameters of NSCLC revealed correlations between the expression of each with tumor grade, lymph node metastasis, and tumor node metastasis. The overall survival of patients with MACC1- or ALDH1-positive NSCLC tumors was significantly lower than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or ALDH1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with NSCLC.

Conclusions: MACC1 and ALDH1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for NSCLC.

Keywords: ALDH1; CSCs; MACC1; NSCLC; Prognosis.

Fig. 1

Representative results of MACC1 and ALDH1 in non-small cell lung cancer and control group. a: Control bronchiolar epithelial cells expressed MACC1 in the cytoplasm. b: MACC1 predominantly localized in the cytoplasm in moderately grade of squamous cell carcinoma (MACC1 × 400). c: Control bronchiolar epithelial cells expressed ALDH1 in the cytoplasm. d: ALDH1 predominantly localized in the cytoplasm in moderately grade of squamous cell carcinoma (ALDH1 × 400)

Fig. 2

Kaplan-Meier survival analysis by MACC1 and ALDH1 status (n = 240). The y-axis represents the percentage of patient; the x-axis, their survival in months. The green line represents patients with positive expression of MACC1 (a) or ALDH1 (b) with a trend of worse survival time than the blue line representing the negative MACC1 group or ALDH1 group (P < 0.001). Mean survival time was 42.1 months for the positive expression of MACC1 group and 54.2 months for the negative MACC1 group. Mean survival time was 42.0 months for the positive expression of ALDH1 group and 52.1 months for the negative ALDH1 group

Fig. 3

Kaplan-Meier survival analysis by grade, lymph node metastasis, and TNM stages status (n = 240). The y-axis represents the percentage of patient; the x-axis, their survival in months. a The green line represents patients with moderate grade of NSCLC with a trend of worse survival time than the blue line representing the well grade group (P < 0.001). Mean survival time was 44.1 months for the moderate grade of NSCLC group and 58.2 months for the well grade of NSCLC group. The brown line represents patients with poor grade of NSCLC with a trend of worse survival time than the blue line representing the well grade group (P = 0.027). b The green line represents patients with LNM of NSCLC with a trend of worse survival time than the blue line representing the no LNM group (P = 0.001). c The green line represents patients with stageII of NSCLC with a trend of worse survival time than the blue line representing the stageIgroup (P = 0.010). The brown line represents patients with stage III of NSCLC with a trend of worse survival time than the blue line representing the stage I group (P < 0.001). The brown line represents patients with stage III of NSCLC with a trend of worse survival time than the blue line representing the stage II group (P = 0.040)