8535c577f393e5b00337e27c341716f0 pmc_10741005.pdf 775a4c3e8f915b69dbe7ef7c18ca3266243d5dda pmc_10741005.pdf c057f2fff3cffa4d03429f83775c7898179b2af24b8700fe8676fa9de955d9b8 pmc_10741005.pdf Title: Secreted Protein Acidic and Rich in Cysteine (SPARC) Polymorphisms in Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer Patients Subject: Secreted protein acidic and rich in cysteine (SPARC) expression has been proposed as a prognostic and predictive biomarker for some cancer types, but knowledge about the predictive value of SPARC polymorphisms in the context of neoadjuvant therapy for breast cancer (BC) is lacking. In 132 HER2-negative BC patients treated with neoadjuvant chemotherapy, we determined polymorphisms in the SPARC gene and analyzed their association with outcome. We also determined SPARC protein expression in tumor tissue. SPARC rs19789707 was significantly associated with response to treatment according to the Miller and Payne system in the breast (multivariate: odds ratio (OR), 3.81; p = 0.028). This association was significant in the subgroup of patients with luminal tumors (univariate: p = 0.047). Regarding survival, two SPARC variants showed significant associations with event-free survival: the rs19789707 variant in the subgroup of luminal A tumors (univariate: p = 0.006), and the rs4958487 variant in the subgroup of luminal B tumors (univariate: p = 0.022). In addition, SPARC rs4958487, rs10065756, and rs12153644 were significantly correlated with SPARC protein expression. Our findings suggest that SPARC polymorphisms could be good predictors of treatment response and survival in BC patients treated with neoadjuvant chemotherapy, especially those with luminal tumors. Keywords: SPARC; breast cancer; polymorphisms; biomarker; neoadjuvant therapy Author: Cristina Arqueros, Juliana Salazar, Alberto Gallardo, Marta Andrés, Ariadna Tibau, Olga Lidia Bell, Alícia Artigas, Adriana Lasa, Teresa Ramón y Cajal, Enrique Lerma and Agustí Barnadas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Dec 6 12:52:15 2023 CET ModDate: Wed Dec 6 13:07:45 2023 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 917697 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 10 0 YSCVAH+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 DEQRNL+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 AVWLOI+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 NYPDQC+URWPalladioL-BoldItal Type 1 Custom yes yes no 28 0 XWOCXD+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 EBFBTV+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 OYLTVA+CMSY10 Type 1 Builtin yes yes no 75 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 79 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 97 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 101 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 105 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 109 0 BCDLEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 116 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 132 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 136 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 140 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 144 0 BCDJEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 151 0 BCDKEE+PalatinoLinotype-BoldItalic CID TrueType Identity-H yes yes yes 158 0 BCDLEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 166 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-05-03 02:40:37 CEST RepresentationInformation: pmc_10741005.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-04-24 02:38:32 CEST Size: 917697 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 390 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Population Destination: subsection.2.1 Item: Title: Study Design and Outcome Evaluation Destination: subsection.2.2 Item: Title: Genetic Studies Destination: subsection.2.3 Item: Title: Immunohistochemical Studies Destination: subsection.2.4 Item: Title: Statistical Analyses Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Clinical Results Destination: subsection.3.1 Item: Title: SPARC Polymorphisms and Clinical Pathological Characteristics Destination: subsection.3.2 Item: Title: SPARC Polymorphisms and Pathological Response Destination: subsection.3.3 Item: Title: SPARC Polymorphisms and Survival Destination: subsection.3.4 Item: Title: SPARC Polymorphisms and SPARC Expression Destination: subsection.3.5 Item: Title: SPARC Expression and Clinical Outcomes Destination: subsection.3.6 Item: Title: In Silico Analysis Destination: subsection.3.7 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.A. Info: Title: Secreted Protein Acidic and Rich in Cysteine (SPARC) Polymorphisms in Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer Patients Author: Cristina Arqueros, Juliana Salazar, Alberto Gallardo, Marta Andrés, Ariadna Tibau, Olga Lidia Bell, Alícia Artigas, Adriana Lasa, Teresa Ramón y Cajal, Enrique Lerma and Agustí Barnadas Subject: Secreted protein acidic and rich in cysteine (SPARC) expression has been proposed as a prognostic and predictive biomarker for some cancer types, but knowledge about the predictive value of SPARC polymorphisms in the context of neoadjuvant therapy for breast cancer (BC) is lacking. In 132 HER2-negative BC patients treated with neoadjuvant chemotherapy, we determined polymorphisms in the SPARC gene and analyzed their association with outcome. We also determined SPARC protein expression in tumor tissue. SPARC rs19789707 was significantly associated with response to treatment according to the Miller and Payne system in the breast (multivariate: odds ratio (OR), 3.81; p = 0.028). This association was significant in the subgroup of patients with luminal tumors (univariate: p = 0.047). Regarding survival, two SPARC variants showed significant associations with event-free survival: the rs19789707 variant in the subgroup of luminal A tumors (univariate: p = 0.006), and the rs4958487 variant in the subgroup of luminal B tumors (univariate: p = 0.022). In addition, SPARC rs4958487, rs10065756, and rs12153644 were significantly correlated with SPARC protein expression. Our findings suggest that SPARC polymorphisms could be good predictors of treatment response and survival in BC patients treated with neoadjuvant chemotherapy, especially those with luminal tumors. 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