It has been largely demonstrated that

It has been largely demonstrated that several clinico-pathological factors influence ovarian cancer patients' prognosis, including residual tumor at primary cytoreductive surgery, FIGO stage, tumor grading, cancer histology and performance status [3,4]. Nevertheless, the recent awareness achieved in the field of ovarian cancer disease is that it comprises several genomically and phenotypically distinct subgroups of tumors with heterogeneous clinical behaviours [5]. Although distinct molecular subtypes of ovarian cancers have been recognized, this knowledge is yet to be translated into effective changes of treatment for the patients. Thus, there is still urgent need to identify poor prognostic bimolecular markers, which are able to predict outcome for heterogeneous biological subgroups of patients. In this context, the cancer stem-like Macitentan (CSCs) theory has acquired increasing interest during the last decade in the understanding of regulation of cancer growth and intratumoral heterogeneity. Multiple evidence, indeed, have shown that, within the tumor mass, a distinct cancer cell population has self-renewal and differentiation properties [6] and that CSCs are associated with increased tumorigenesis potential, cancer metastatization and chemoresistance [7,8]. In ovarian cancer, different molecules have been identified as potential cancer stem-like cells biomarkers, such as, CD133, CD144, CD24, CD117, ABCG2 and Aldehyde dehydrogenase-1 (ALDH1) [9,10], although it remains unclear if all markers are associated with a single cell type. Aldehyde dehydrogenases are a group of enzymes involved in the dehydrogenation of aldehydes to their corresponding carboxylic acids. Up to date, nineteen different human ALDH isozymes have been identified. ALDH1 gene, in particular, encodes a distinct enzyme isoform localized in the cytoplasm and plays a key role not only in the regulation of aldehydes metabolism but also in cell differentiation, proliferation [11,12] and motility [13]. ALDH1-expressing cancer cells were found to exhibit stem-like properties, due to their self-renewal, high proliferative and high coloning capacities, as well as cancer initiating properties, in different solid tumor setting [[14], [15], [16], [17], [18]], including ovarian cancer [19]. Recently published meta-analysis indicated that ALDH1 is a promising biomarker for breast [20], head and neck [21], lung [22] and colorectal cancer [23] prognosis but, in ovarian cancer setting, findings regarding its prognostic value are still controversial [[24], [25], [26]], thus leading to the need of clarifying the role of this molecular target in predicting ovarian cancer patients' outcome.
Methods
Results In total, 233 studies were retrieved through the literature search. Among these, 34 (14.6%) studies were removed as duplicates. Further 181 papers (77.7%) were excluded after title and abstract evaluation, being not English-language original reports, studies not regarding ovarian cancers, studies performed on animals, review papers or studies not applying immunohistochemistry (IHC) method for ALDH1 expression evaluation. Five (2.1%) studies were successively excluded after full-text evaluation: two were excluded because the association between ALDH1 expression levels and patients' survival or patients' clinico-pathological characteristics was not evaluated [27,28]; another one was excluded because ALDH1 expression levels were not dichotomized as “high” or “low” [29]; one study because the Authors did not apply IHC to evaluate ALDH1 expression [30] and another study was excluded because different solid tumor types were analyzed and survival data on ovarian cancer patients' could not be deduced [31]. Thirteen (5.6%) studies remained for comparison at the end of the selection process. The PRISMA flow chart summarizing the process of evidence acquisition was shown in Fig. 1. The flow chart maps out the number of studies identified, screened, included, and excluded as well as the reasons for exclusions.