ALDH1A1 expression is associated with poor differentiation, ‘right-sidedness’ and poor survival in human colorectal cancer

Abstract

BackgroundAldehyde dehydrogenase 1A1 (ALDH1A1) encodes an enzyme that oxidizes aldehydes to their corresponding carboxylic acids. In colorectal cancer ALDH1A1 marks cancer stem cells and plays putative roles in tumor progression and drug resistance. However, the potential value of ALDH1A1 as a diagnostic marker or target for therapy remains unclear. Here, we have analyzed ALDH1A1 mRNA and protein levels in relation to clinical, histopathological and molecular tumor features in large series of human colorectal cancer.MethodsALDH1A1 protein levels were determined by immunohistochemistry in a series of primary colorectal tumors and their corresponding liver metastases (n = 158). ALDH1A1 mRNA levels were analyzed in several large patient cohorts of colorectal cancer. ALDH1A1 mRNA and protein levels were then related to overall survival and to clinical, histopathological and molecular tumor features.ResultsHigh levels of ALDH1A1 were associated with a poorly differentiated histology and a right-sided tumor location, but not to a mesenchymal-like molecular subtype. Liver metastases contained significantly higher levels of ALDH1A1 compared to the corresponding primary tumors. Radio- and/or chemotherapy prior to tumor resection was associated with increased ALDH1A1 levels regardless of the molecular subtype. Finally, ALDH1A1 protein expression in primary tumors and metastases correlated with shorter overall survival.ConclusionsALDH1A1 expression is associated with features of poor prognosis, including a poorly differentiated histology and ‘right-sidedness’ of the primary tumor, and with shorter overall survival. ALDH1A1 is also highly expressed in therapy-surviving tumors and in liver metastases. These results warrant further research into the potential value of targeting ALDH1A1 in order to improve the efficacy of standard treatment and thereby preventing tumor recurrence.

The prognostic significance of ALDH1A1 expression in early invasive breast cancer

“…ALDH1A1 plays a major role in the progression of several solid tumours. 6,[29][30][31] Ginestier et al 4 have reported that ALDH1A1 is a specific marker for isolated BCSC. Furthermore, ALDH1A1 has been reported as being a marker for CSC in solid cancers such as lung 13 and colorectal cancer.…”

Identifying the Salient Genes in Microarray Data: A Novel Game Theoretic Model for the Co-Expression Network

“…List of well-validated biomarkers for colon cancer stem cells from the validated experimental setup (along with a review for more reference and importance) retrieved from the CellMarker database [39] and populated thereafter (for the ease of reading). The gene M31994 encodes Aldehyde dehydrogenase 1A1 (ALDH1A1), which catalyzes aldehydes to their corresponding carboxylic acids through the oxidation process [44]. It has also been enunciated that a considerable amount of ALDH1A1 enrichment occurs in colon cancer [45,46].…”

“…The gene M31994 encodes Aldehyde dehydrogenase 1A1 (ALDH1A1), which catalyzes aldehydes to their corresponding carboxylic acids through the oxidation process [ 44 ]. It has also been enunciated that a considerable amount of ALDH1A1 enrichment occurs in colon cancer [ 45 , 46 ].…”

Retinoids in Cutaneous Squamous Cell Carcinoma

“…ALDH activity is high in cancer stem cells (CSC; aka tumor initiating cell) and is used to isolate these cells from a number of solid organ tumors [182][183][184][185][186]. Human tumors with increased ALDH1A1 positive cells measured at the protein level are associated with increased risk of recurrence in non-small cell lung cancer [187], enhanced invasiveness in nasopharyngeal carcinoma [188], and poor survival in bladder cancer [189], papillary thyroid carcinoma [190], head and neck cancer [191], esophageal SCC [192], colorectal can-cer [193], and breast cancer [194]. On the other hand, high ALDH1A1 levels predicted better outcomes in gastric cancer [195].…”