Investigation of Transcript Variant 6 of TPD52L2 as a Prognostic and Predictive Biomarker in Basal-Like MDA-MB-231 and MDA-MB-453 Cell Lines for Breast Cancer

Abstract

Background. Basal-like breast cancer (BLBC) exhibits worse pathological features than other breast cancer subtypes, and patients diagnosed with BLBC have short disease-free and overall survival times. Thus, the identification of novel biomarkers and therapeutic targets for BLBC is of upmost importance. Although TPD52L2 is upregulated in multiple cancers, little is known about its roles in BLBC. Methods. RNA levels were analyzed between breast cancer tissues and paired adjacent normal tissues using RNA-seq data from The Cancer Genome Atlas (TCGA). TPD52L2 stable knockdown and inducible knockout cell lines were established using basal-like MDA-MB-231 and MDA-MB-453 cell lines. Cell proliferation assays in vitro and tumor growth analysis in vivo were performed to determine the function of TPD52L2 during BLBC progression. Transwell assays were used to estimate the regulatory effect of TPD52L2 on BLBC cell migration. The expression profile of all tpd52l2 transcripts was analyzed to assess the functional protein isoform. Association of transcript variant 6 (V6) expression with pathological parameters was carried out using the clinical data of the BRCA cohort. Results. We identified V6 of TPD52L2 as a novel biomarker and regulator of BLBC progression. TPD52L2 is upregulated in BLBCs and associated with patient outcomes. TPD52L2 knockdown suppresses tumor growth, and V6 correlates with cancer-related phenotypes in BLBC. Clinical data further proved that V6 is associated with different pathological features, such as pathological stage and pathological tumor status, and independently predicts patient outcomes and responses to therapies. Conclusions. Our findings demonstrate that V6 of TPD52L2 is a novel biomarker for BLBC patients. V6 promotes cell proliferation and migration and has marked oncogenic roles in determining the malignant phenotypes of BLBC.