Profillin-1 and Transgelin-2: Actin Binding Proteins Expression in Early and Advanced Stages of Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.

BACKGROUND: Triple-negative breast cancer (TNBC) is known for its more aggressive clinical behavior, poor prognosis, and distinctive patterns of metastasis. Neoadjuvant chemotherapy (NAC) can influence both tumor cells and the tumor microenvironment. Emerging evidence highlights the critical role of actin cytoskeletal dynamics in cancer progression. AIMS: This study aimed to explore the expression of two actin binding proteins, profilin-1 (PFN-1) and transgelin-2 (TAGLN-2), before and after NAC. Their prognostic significance, particularly in response to NAC in TNBC, has not been fully elucidated. Their expression patterns may provide valuable insight into their prognostic value and treatment response. METHODS AND RESULTS: This quasi-experimental study included 54 females (aged 24-45 years) diagnosed with TNBC pre- and post-treated NAC and age matched healthy donors (n = 30). The strategy encompasses sequential high-resolution Reverse-Phase Liquid Chromatography Mass Spectrometry (RPLC-MS/MS) for identification of peptides followed by ELISA and RT-qPCR. An in silico analysis, STRING and KEGG analysis were also employed. The PFN-1 protein and gene expression in early stages (I & II) of pre-NAC were significantly (p = 0.0001) higher. However, in the post-NAC patients with advanced stages, expression was reduced. The TGLN-2 protein concentration was significantly higher (p = 0.0001) in the pre-NAC group at advanced stages compared with post-NAC patients. Gene expression of TGLN-2 is highly overexpressed in both groups at advanced stages. Moreover, tumor suppressor gene PTEN was downregulated at early stages of pre and post-NAC groups and upregulated at advanced stages of post-NAC. STRING and KEGG analysis showed that PFN-1 and TGLN-2 both displayed association with regulation of actin cytoskeleton. CONCLUSION: Aberrantly expression of actin binding proteins, PFN-1 and TAGLN-2 and tumor suppressor gene PTEN in pre and post-NAC patients in different tumor stages compared with healthy individuals can provide valuable prognostic information and may have potential as a therapeutic target. The observed interactions of PFN-1 with VASP and potential crosstalk with TAGLN-2 point toward their collective role in actin cytoskeleton regulation and tumorigenesis.