HighSLC20A1Expression Is Associated With Poor Prognoses in Claudin-low and Basal-like Breast Cancers

Abstract

Background/Aim: SLC20A1 has been identified as a prognostic marker in ER+ breast cancer. However, the role of SLC20A1 expression in breast cancer subtypes other than the ER+ types remains unclear. Materials and Methods: Genomics datasets were downloaded and analyzed, and the effect of SLC20A1 knockdown using targeted siRNA on cell viability and tumor-sphere formation was assessed. Results: SLC20A1 high patients with ER+, claudin-low or basal-like breast cancers showed poor prognoses. SLC20A1 high patients treated with radiotherapy had poor clinical outcomes. SLC20A1 knockdown suppressed the viability of MDA-MB 231 (claudin-low), MDA-MB 468 (basal-like) and MCF-7 (ER+) cells, and tumor-sphere formation by ALDH1 high cells. These results suggest that SLC20A1 is involved in cancer progression and contributes to clinical outcomes in patients with ER+, claudin-low and basal-like breast cancers. Conclusion: SLC20A1 is a potential prognostic marker and therapeutic target in ER+, claudin-low and basal-like breast cancers.Breast cancer is the most commonly occurring cancer among women worldwide, with 2.1 million new cases (24.2% of all cancers in women) and 0.6 million cancer-related deaths (15.0% of all cancer-related deaths among woman) annually (1). Breast cancer is classified using immunohistochemistry (IHC) and gene expression patterns (PAM50) (2-7). Based on IHC, breast cancer is classified into four types: ER+ and/or PgR+ HER2-type, ER+ and/or PgR+ HER2+ type, ER-and PgR-HER2+ type and triple negative type (TNBC). Based on PAM50, breast cancer is classified into at least six subtypes: normal-like, luminal A, luminal B, HER2-enriched, claudin-low and basal-like (2-7). Among these, the luminal A and luminal B types express ER (8, 9), and some luminal B and HER2-enriched types express HER2 (4, 8-11). Many claudin-low and basal-like types overlap with the TNBC type (6,(12)(13)(14).Breast cancer treatment mainly entails surgery, radiotherapy and drug therapy, which may include chemotherapy, endocrine therapy and/or molecular target therapy. Overall, breast cancer prognosis is good. Endocrine therapy is selected against ER+ type and a HER2-targeted antibody, such as trastuzumab, is used to treat HER2 type (11,15,16). However, there is no effective drug or molecular targeted therapy for TNBC or its overlapping claudin-low and basal-like types. Consequently, those patients are treated only with surgery, radiotherapy and chemotherapy, and have poor prognoses (6,13,(15)(16)(17). Moreover, it is also known that in some of these cases, chemo-and/or radiotherapy actually stimulates cancer progression (18)(19)(20). It is therefore essential to identify effective prognostic markers and molecular targets that can be exploited for the treatment of the claudin-low and basallike breast cancer subtypes.A major hurdle that must be overcome for therapy to be effective against the claudin-low and basal-like subtypes is 43 This article is freely accessible online.

Construction and evaluation of a nomogram for predicting survival in patients with lung cancer

“…As a gene that is overexpressed in breast, bladder, colorectal, head and neck, liver, lung, and esophageal cancers [ 40 ], SPP1 has the potential to influence not only the occurrence and progression of LUAD, but also to serve as an independent prognostic marker and a novel therapeutic target [ 41 – 43 ]. High SLC20A1 expression is associated with poor prognoses in basal-like breast cancers, longue cancer and esophageal adenocarcinoma [ 44 – 46 ]. CENPH was found to drive the molecular changes during the pathologic stages of LUAD [ 47 ], and patients with a higher expression level of CENPH tended to have a poorer OS [ 25 ].…”

GLO 1 and PKCλ Regulate ALDH1-positive Breast Cancer Stem Cell Survival

“…Expression levels of GLO 1 (reporter, A_32_P53822), PKCλ (reporter, A_23_P18392), and ALDH1A3 (reporter, A_23_P205950) mRNA are presented using the log2 median-centered ratio for both normal and cancerous tissues. Another set of gene expression data was downloaded from the cBioportal in June 2021 and analyzed as previously described (9,23,24,37,53,58,59). Briefly, the Molecular Taxonomy of Breast Cancer International Consortium dataset (n=1,904) was downloaded from cBioPortal (60,61).…”

“…The MDA-MB-157 and MDA-MB-468 human basal-like breast cancer cell lines were obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA). The cells were then cultured as previously described (9,23,24,37,53,59). Control knockout (KO) and PKCλ KO clones established using the CRISPR-Cas9 system were cultured and maintained as previously described (9).…”

“…ALDEFLUOR assay. ALDH1 high cells were isolated from MDA-MB-157 and MDA-MB-468 cells using an ALDEFLUOR™ assay kit (Stem Cell Technology, Vancouver, BC, Canada) according to the manufacturer's protocol as previously described (9,23,24,53,59). As a negative control for the ALDEFLUOR assay, cells were incubated with the ALDH1 inhibitor diethylaminobenzaldehyde (DEAB).…”

“…Tumor-sphere culture. Tumor-spheres were grown as previously described (9,23,24,37,53,59). Briefly, cells (1×10 3 /well) were seeded into 96-well ultralow attachment plates (Greiner Bio-One, Kremsmünster, Austria) and incubated for 24 h. The cells were cultured for 6 days in the presence of TLSC702 and ANF.…”