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

Abstract

BackgroundTumor 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.MethodsThe expression levels of both MACC1 and ALDH1 in 240 whole tissue sections of NSCLC were examined by immunohistochemistry. Clinical data were also collected.ResultsMACC1 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.ConclusionsMACC1 and ALDH1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for NSCLC.

MACC1 silencing inhibits cell proliferation and induces cell apoptosis of lung adenocarcinoma cells through the β-catenin pathway

“…Our study proves that MACC1 is elevated in patients with lung adenocarcinoma and that MACC1 knockdown significantly attenuates proliferation capability, induces G0/ G1 phase arrest and stimulates cell apoptosis in vitro in lung adenocarcinoma cells by regulating the β-catenin pathway. MACC1 elevated expression and prognostic value have been demonstrated in multiple tumors [6,10,[14][15][16][17][18], and our results of tissue samples and database search coincide with the well-documented NSCLC data provided by Wang et al and Zhou et al [10,11]. Numerous studies on the correlation between MACC1 expression and clinical pathological parameters indicate its prognostic value in a variety of cancers [5,8,19].…”

“…However, MACC1 knockdown can inhibit cell proliferation, colony formation, invasion, arrest the cell cycle in the G0/G1 phase and induce cell apoptosis in human osteosarcoma [9]. While it has been reported that high MACC1 levels predict worse prognosis in NSCLC patients [10][11][12], its function and underlying molecular mechanisms remain unclear.…”

Evaluation of the correlation of MACC1, CD44, Twist1, and KiSS-1 in the metastasis and prognosis for colon carcinoma

“…MACC1 is also reported to not only promote tumor cell proliferation, invasion, and dissemination by inducing epithelial-mesenchymal transition (EMT) in vitro [ 5 , 6 ] but also to induce tumor cell growth, invasion, and metastasis in vivo [ 3 , 7 ]. It has been demonstrated that MACC1 should be defined as a prognostic and metastatic biomarker for various cancers [ 8 ].…”

“…CSCs have the characteristics of self-renewal, proliferation, invasiveness, and metastasis. They are responsible for cancer initiation and natural resistance to therapy [ 8 – 12 ]. CD44 is not only a common biomarker of CSCs in cancers, such as colorectal cancer, lung cancer, and glioblastoma [ 13 – 15 ], but also a receptor of hyaluronan.…”

Spectrum of ALDH1 mRNA in smokers and non-smokers with adenocarcinoma or squamous cell lung carcinoma

“…The ALDH1 family of enzymes (namely ALDH1A1, ALDH1A2 and ALDH1A3) is a cytosolic detoxifying enzyme responsible for the oxidation of (retin)aldehydes into retinoids [5]. It has been widely used to isolate cancer stem cells [6].…”