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
报道一例以共济失调、全身震颤、眼肌麻痹、痉挛性截瘫为临床表现的成人起病的常染色体隐性遗传的复杂型遗传性痉挛性截瘫(hereditary spastic paraplegias, HSP)。患者通过全外显子基因测序,找到DDHD2基因[c.335G>A, p.R112Q]的纯...报道一例以共济失调、全身震颤、眼肌麻痹、痉挛性截瘫为临床表现的成人起病的常染色体隐性遗传的复杂型遗传性痉挛性截瘫(hereditary spastic paraplegias, HSP)。患者通过全外显子基因测序,找到DDHD2基因[c.335G>A, p.R112Q]的纯合突变,提示该突变可能与该患者的临床表现相关。本例报告为复杂型HSP的遗传基础提供了新的见解,并强调了基因检测在此类罕见疾病诊断中的重要性。We report a case of adult-onset autosomal recessive complex hereditary spastic paraplegia (HSP), characterized by a combination of ataxia, generalized tremor, ophthalmoplegia, and spastic paraplegia. Genetic analysis through whole-exome sequencing identified a homozygous mutation in the DDHD2 gene (c.335G>A, p.R112Q), which is likely responsible for the observed clinical manifestations. This case report provides new insights into the genetic basis of complex HSP and highlights the importance of genetic testing in the diagnosis of such rare diseases.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.
文摘报道一例以共济失调、全身震颤、眼肌麻痹、痉挛性截瘫为临床表现的成人起病的常染色体隐性遗传的复杂型遗传性痉挛性截瘫(hereditary spastic paraplegias, HSP)。患者通过全外显子基因测序,找到DDHD2基因[c.335G>A, p.R112Q]的纯合突变,提示该突变可能与该患者的临床表现相关。本例报告为复杂型HSP的遗传基础提供了新的见解,并强调了基因检测在此类罕见疾病诊断中的重要性。We report a case of adult-onset autosomal recessive complex hereditary spastic paraplegia (HSP), characterized by a combination of ataxia, generalized tremor, ophthalmoplegia, and spastic paraplegia. Genetic analysis through whole-exome sequencing identified a homozygous mutation in the DDHD2 gene (c.335G>A, p.R112Q), which is likely responsible for the observed clinical manifestations. This case report provides new insights into the genetic basis of complex HSP and highlights the importance of genetic testing in the diagnosis of such rare diseases.
