title: Altered glycometabolism affects both clinical features and prognosis of triple-negative and neoadjuvant chemotherapy-treated breast cancer.
abstract: Glycometabolism is a distinctive aspect of energy metabolism in breast cancer, and key glycometabolism enzymes/pathways (glycolysis, hexosamine biosynthetic pathway, and pentose phosphate pathway) may directly or indirectly affect the clinical features. In this study, we analyzed the particular correlation between the altered glycometabolism and clinical features of breast cancer to instruct research and clinical treatment. Tissue microarrays containing 189 hollow needle aspiration samples and 295 triple-negative breast cancer tissues were used to test the expression of M2 isoform of pyruvate kinase (PKM2), glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucose-6-phosphate dehydrogenase (G6PD), and p53 by immunohistochemistry and the intensity of these glycometabolism-related protein was evaluated. Chi-square test, Kaplan-Meier estimates, and Cox proportional hazards model were used to analyze the relationship between the expression of these factors and major clinical features. PKM2, GFPT1, and G6PD affect the pathologic complete response rate of neoadjuvant chemotherapy patients in different ways; pyruvate kinase muscle isozyme 2 (PKM2) and G6PD are closely associated with the molecular subtypes, whereas GFPT1 is correlated with cancer size. All these three factors as well as p53 have impacts on the progression-free survival and overall survival of triple-negative breast cancer patients. Cancer size shows significant association with PKM2 and GFPT1 expression, while the pN stage and grade are associated with PKM2 and G6PD expression. Our study support that clinical characteristics are reflections of specific glycometabolism pathways, so their relationships may shed light on the orientation of research or clinical treatment. The expression of PKM2, GFPT1, and G6PD are hazardous factors for prognosis: high expression of these proteins predict worse progression-free survival and overall survival in triple-negative breast cancer, as well as worse pathologic complete response rate in neoadjuvant chemotherapy breast cancer. However, p53 appears as a protective factor only in the patients receiving neoadjuvant chemotherapy. All the four proteins, PKM2, GFPT1, G6PD and p53, are prognostic markers of breast cancer. The correlation among them suggests that there may be crosstalk of the four proteins in breast cancer.
authors.affiliation: Department of Internal Medicine, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Tieying
authors.initials: T
authors.lastname: Dong
authors.affiliation: Department of Internal Medicine, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Kang
authors.affiliation: Cancer Research Institute, Harbin Medical University, Harbin, China.|Cancer Research Institute of Heilongjiang, Harbin, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Internal Medicine, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Internal Medicine, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Qijia
authors.initials: Q
authors.lastname: Xuan
authors.affiliation: Department of Internal Medicine, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, Heilongjiang Province, 150081, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Liu
authors.affiliation: The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, Heilongjiang Province, 150081, China. zqyxsci@126.com.|Cancer Research Institute of Heilongjiang, Harbin, China. zqyxsci@126.com.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D013963:Thyroid Hormones / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D005954:Glucosephosphate Dehydrogenase; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D008565:Membrane Proteins; D013963:Thyroid Hormones; D016159:Tumor Suppressor Protein p53; D000097810:Thyroid Hormone-Binding Proteins; C495901:TP53 protein, human; C497511:GFPT1 protein, human
keywords: Breast cancer; Glycolysis; Hexosamine biosynthetic pathway; Neoadjuvant chemotherapy; Pentose phosphate pathway; Prognostic and predictive value