Abstract
BackgroundSpalt-like transcription factor 4 (SALL4) and aldehyde dehydrogenase1 family member A1 (ALDH1A1) expressing cells have been characterized as possessing stem cell-like properties known as cancer stem cell marker in serous ovarian carcinoma (SOC).MethodsThe association between SALL4 and ALDH1A1 was observed based on literature review and bioinformatics tools. Therefore, this study aimed to investigate the association between the co-expression of SALL4/ALDH1A1 proteins and clinicopathological parameters and their prognostic value in SOC patients using immunohistochemical staining on tissue microarrays (TMAs). Furthermore, benign tumors and normal tissue samples were compared with the expression of the tumor tissue samples.ResultsIncreased co-expression of SALL4/ALDH1A1 was found to be significantly associated with the advanced FIGO stage (P = 0.047), and distant metastasis (P = 0.028). The results of Kaplan–Meier survival analysis indicated significant differences between disease- specific survival (DSS; P = 0.034) or progression-free survival (PFS; P = 0.018) and the patients with high and low co-expression of SALL4/ALDH1A1, respectively. Furthermore, high level co-expression of SALL4/ALDH1A1 was a significant predictor of worse DSS and PFS in the univariate analysis. The data also indicated that the co-expression of SALL4/ALDH1A1 was an independent prognostic factor affecting PFS. Moreover, the co-expression of SALL4/ALDH1A1 added prognostic values of DSS in patients with SOC who had grade III versus grade I in multivariate analysis.ConclusionsOur data demonstrated that high co-expression of SALL4/ALDH1A1 was found to be significantly associated with tumor aggressiveness and worse DSS or PFS in SOC patients. Therefore, co-expression of SALL4/ALDH1A1 may serve as a potential prognostic biomarker of cancer progression in these cases.
Highlights
Spalt-like transcription factor 4 (SALL4) and aldehyde dehydrogenase1 family member A1 (ALDH1A1) expressing cells have been characterized as possessing stem cell-like properties known as cancer stem cell marker in serous ovarian carcinoma (SOC)
The protein-protein interaction (PPI) network showed that SALL4 and ALDHI1A1 have interactions with other important cancer stemness genes and cancer stem cells (CSCs) markers such as NANOG, POUF5 (OCT4), SOX2, CD44, and CD133 (PROM1) as shown in Fig.2 A and B
SALL4 was involved in PTEN regulation, and AKT signaling and activation genes were related to the proliferation pathway, while ALDH1A1 was associated with the metabolism pathways
Summary
Spalt-like transcription factor 4 (SALL4) and aldehyde dehydrogenase family member A1 (ALDH1A1) expressing cells have been characterized as possessing stem cell-like properties known as cancer stem cell marker in serous ovarian carcinoma (SOC). EOC as a serous ovarian carcinoma (SOC), is diagnosed at advanced stages of disease in 70% of cases because of non-specific sign and symptoms of ovarian tumors [3] For these patients, surgery followed by chemotherapy remains the standard of care [4]. There are some common serum tumor FDA approved biomarkers for screening high-risk OC women, including carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), ova, and overa [5]. These biomarkers are not applied as a prognostic biomarker and they have low sensitivity and low accuracy [6]. An optimal biomarker with high accuracy is essentially needed that improves the prognostic biomarker
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