Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph ...Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph node metastases or even distant organ metastasis.Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence,there is a significant gap in research on luminal A breast cancer with high invasiveness.This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms.Methods:In this study,we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2(DDHD2).We then evaluated the association between DDHD2 expression and patient prognosis,genetic material changes,and transcriptional,translational,and immune responses in luminal A breast cancer.We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms.Results:The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases.Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration,regulating cell proliferation and apoptosis cycles,and suppressing immune responses.Moreover,a pathway through which DDHD2 inhibited immunity was preliminarily verified.Conclusions:The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer.Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition,DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.展开更多
Chondroitin sulfate synthase 2(CHPF)is characterized as an oncogenic and poor prognosis-related gene in breast cancer.However,this gene has alternative splicing products encoding proteins of different lengths.Breast c...Chondroitin sulfate synthase 2(CHPF)is characterized as an oncogenic and poor prognosis-related gene in breast cancer.However,this gene has alternative splicing products encoding proteins of different lengths.Breast cancer is a group of heterogeneous tumors with distinct clinical and genomic characteristics.In this study,we explored the expression profile and prognostic value of the two transcripts of CHPF using data from The Cancer Genome Atlas(TCGA)-BRCA.The functional regulation of the two transcripts was also studied in MCF-7 and BT-474 cells.Among the two transcripts of CHPF,ENST00000535926 expression was significantly upregulated in the tumor samples and was the dominant isoform.ENST00000535926,but not ENST00000243776 upregulation,was associated with significantly worse progression-free survival(PFS)and disease-specific survival(DSS)in luminal A/B cases.However,no significant association was observed in PFS or DSS in other Prediction Analysis of Microarray 50(PAM50)subgroups.CHPF isoform 2 protein(encoded by ENST00000535926)significantly elevated the expression of P3H1 and RCN3 at the mRNA and protein levels in MCF-7 and BT-474 cells.The effect of ENST00000535926 was significantly stronger than ENST00000243776 in promoting tumor cell colony formation.The expression of P3H1 and RCN3 was negatively correlated with CD8+T cell infiltration but was positively correlated with cancer-associated fibroblast infiltration in luminal A/B tumors.In summary,this study revealed that ENST00000535926 is an unfavorable prognosis-related and tumor-promoting transcript of the CHPF gene in luminal A/B breast cancer.展开更多
Objective： We retrospectively analyzed the clinical prognostic value of the 8th edition of the American Joint Committee on Cancer （AJCC） staging system for luminal A breast cancer. Methods： Using both the anatomic...Objective： We retrospectively analyzed the clinical prognostic value of the 8th edition of the American Joint Committee on Cancer （AJCC） staging system for luminal A breast cancer. Methods： Using both the anatomic and prognostic staging in the 8th edition of AJCC cancer staging system, we restaged patients with luminal A breast cancer treated at the Breast Disease Center, Peking University First Hospital from 2008 to 2014. Follow-up data including 5-year disease free survival （DFS）, overall survival （OS） and other clinic-pathological data were collected to analyze the differences between the two staging subgroups. Results： This study included 421 patients with luminal A breast cancer （median follow-up, 61 months）. The 5- year DFS and OS rates were 98.3% and 99.3%, respectively. Significant differences in 5-year DFS but not OS were observed between different anatomic disease stages. Significant differences were observed in both 5-year DFS and O S between different prognostic stages. Application of the prognostic staging system resulted in assignment of 175 of 421 patients （41.6%） to a different group compared to their original anatomic stages. In total, 102 of 103 patients with anatomic stage IlA changed to prognostic stage IB, and 24 of 52 patients with anatomic stage lib changed to prognostic stage IB, while 1 changed to prognostic stage liIB. Twenty-two of 33 patients with anatomic stage IliA were down-staged to IlA when staged by prognostic staging system, and the other 11 patients were down-staged to liB. Two patients with anatomic stage IIIB were down-staged to IliA. Among seven padents with anatomic stage IIIC cancer, two were down-staged to IliA and four were down-staged to stage I]IB. Conclusions： The 8th edition of AJCC prognostic staging system is an important supplement to the breast cancer staging system. More clinical trials are needed to prove its ability to guide selection of proper systemic therapy and predict prognosis of breast cancer.展开更多
基金funded by the National Natural Science Foundation of China(no.82103671).
文摘Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph node metastases or even distant organ metastasis.Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence,there is a significant gap in research on luminal A breast cancer with high invasiveness.This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms.Methods:In this study,we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2(DDHD2).We then evaluated the association between DDHD2 expression and patient prognosis,genetic material changes,and transcriptional,translational,and immune responses in luminal A breast cancer.We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms.Results:The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases.Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration,regulating cell proliferation and apoptosis cycles,and suppressing immune responses.Moreover,a pathway through which DDHD2 inhibited immunity was preliminarily verified.Conclusions:The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer.Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition,DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.
基金supported by the Science and Technology Plan Project of Sichuan Province(Provincial Academy and Provincial University Cooperation Project)(2020YFSY0025).
文摘Chondroitin sulfate synthase 2(CHPF)is characterized as an oncogenic and poor prognosis-related gene in breast cancer.However,this gene has alternative splicing products encoding proteins of different lengths.Breast cancer is a group of heterogeneous tumors with distinct clinical and genomic characteristics.In this study,we explored the expression profile and prognostic value of the two transcripts of CHPF using data from The Cancer Genome Atlas(TCGA)-BRCA.The functional regulation of the two transcripts was also studied in MCF-7 and BT-474 cells.Among the two transcripts of CHPF,ENST00000535926 expression was significantly upregulated in the tumor samples and was the dominant isoform.ENST00000535926,but not ENST00000243776 upregulation,was associated with significantly worse progression-free survival(PFS)and disease-specific survival(DSS)in luminal A/B cases.However,no significant association was observed in PFS or DSS in other Prediction Analysis of Microarray 50(PAM50)subgroups.CHPF isoform 2 protein(encoded by ENST00000535926)significantly elevated the expression of P3H1 and RCN3 at the mRNA and protein levels in MCF-7 and BT-474 cells.The effect of ENST00000535926 was significantly stronger than ENST00000243776 in promoting tumor cell colony formation.The expression of P3H1 and RCN3 was negatively correlated with CD8+T cell infiltration but was positively correlated with cancer-associated fibroblast infiltration in luminal A/B tumors.In summary,this study revealed that ENST00000535926 is an unfavorable prognosis-related and tumor-promoting transcript of the CHPF gene in luminal A/B breast cancer.
基金supported by research grants from the Beijing Municipal Commission of Health and Family Planning(No.2009-1011)the Beijing Municipal Science and Technology Commission(No.D090507043409010 and Z131107002213007)the Precision Medicine Special Project of National Key Research and Development Program(No.2016YFC0901302)
文摘Objective： We retrospectively analyzed the clinical prognostic value of the 8th edition of the American Joint Committee on Cancer （AJCC） staging system for luminal A breast cancer. Methods： Using both the anatomic and prognostic staging in the 8th edition of AJCC cancer staging system, we restaged patients with luminal A breast cancer treated at the Breast Disease Center, Peking University First Hospital from 2008 to 2014. Follow-up data including 5-year disease free survival （DFS）, overall survival （OS） and other clinic-pathological data were collected to analyze the differences between the two staging subgroups. Results： This study included 421 patients with luminal A breast cancer （median follow-up, 61 months）. The 5- year DFS and OS rates were 98.3% and 99.3%, respectively. Significant differences in 5-year DFS but not OS were observed between different anatomic disease stages. Significant differences were observed in both 5-year DFS and O S between different prognostic stages. Application of the prognostic staging system resulted in assignment of 175 of 421 patients （41.6%） to a different group compared to their original anatomic stages. In total, 102 of 103 patients with anatomic stage IlA changed to prognostic stage IB, and 24 of 52 patients with anatomic stage lib changed to prognostic stage IB, while 1 changed to prognostic stage liIB. Twenty-two of 33 patients with anatomic stage IliA were down-staged to IlA when staged by prognostic staging system, and the other 11 patients were down-staged to liB. Two patients with anatomic stage IIIB were down-staged to IliA. Among seven padents with anatomic stage IIIC cancer, two were down-staged to IliA and four were down-staged to stage I]IB. Conclusions： The 8th edition of AJCC prognostic staging system is an important supplement to the breast cancer staging system. More clinical trials are needed to prove its ability to guide selection of proper systemic therapy and predict prognosis of breast cancer.
