AIMTo assess differences in protein expression profile associated with shift in carbon source from succinate to benzoate in Serratia sp. DS001 using a proteomics approach.METHODS AND RESULTSA basic proteome map was generated for the soluble proteins extracted from Serratia sp. DS001 grown in succinate and benzoate. The differently and differentially expressed proteins were identified using ImageMaster 2D Platinum software (GE Healthcare). The identity of the proteins was determined by employing MS or MS/MS. Important enzymes such as Catechol 1,2 dioxygenase and transcriptional regulators that belong to the LysR superfamily were identified.CONCLUSIONSNearly 70 proteins were found to be differentially expressed when benzoate was used as carbon source. Based on the protein identity and degradation products generated from benzoate it is found that ortho pathway is operational in Serratia sp. DS001.SIGNIFICANCE AND IMPACT OF THE STUDYExpression profile of the soluble proteins associated with shift in carbon source was mapped. The study also elucidates degradation pathway of benzoate in Serratia sp. DS001 by correlating the proteomics data with the catabolites of benzoate.

OncoTargets and TherapyQ4 · MEDICINE

TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer

Q4 · MEDICINE

ArticleOA

Author: Du, Shaoqian ; Pei, Min ; Wang, Qi ; Liu, Xiaoyue ; Wang, Hongxia ; Chu, Wendi ; Zhou, Tianhao ; Wang, Yongmei ; Wang, Guifeng ; Wang, Chunhe

PurposeTrophoblast cell surface antigen 2 (TROP2) has emerged as a promising target of antibody-drug conjugates (ADCs) for triple-negative breast cancer (TNBC), as well as other breast cancers (BCs). This study aims to investigate the biomarker value of TROP2 for patient-tailoring and prognostic for BC patients, including TNBC.MethodsThe levels of TROP2 expression in 404 Chinese BC tissues on tissue microarrays (TMAs) were quantified by immunohistochemistry and their correlations to the clinicopathological factors and the overall survival rate were analyzed. Also, BC cell lines and patient-derived organoids (PDOs) with different TROP2 expression levels were employed to investigate the correlation between TROP2 expression levels and the therapeutic responses to DS001, a TROP2-directed ADC molecule with stable linker and potent payload.ResultsTROP2 overexpression was identified in significantly more (P = 0.046) tumor tissues (41.08%, 99/241) than normal adjacent tissues (31.29%, 51/163) from Chinese BC patients, and in significantly more (P = 0.024) TNBC patients (59.38%, 19/32) than in other BC types (38.28%, 80/209). BC cell line with the lowest TROP2 expression level failed to respond to DS001 treatment. The levels of TROP2 expression were determined to be significantly correlated with the potencies of DS001 treatment, but not with the overall survival rates of the patients.ConclusionOur results demonstrated that TROP2 could serve as a patient-tailoring and predictive biomarker for ADC therapeutics but not as a general prognostic biomarker to predicate patient survival.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced cancer	IND Approval	CN	Dashi Pharmaceutical (Guangdong) Co., Ltd.	13 Jun 2023
Advanced cancer	IND Approval	CN	Shanghai Institute of Materia Medica Chinese Academy of Sci	13 Jun 2023

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