Study On CCDC69 Interfering With The Prognosis Of Patients With Breast Cancer Through PPAR Signal Pathway

Objective: We explored the relationship between coiled-coil domain-containing protein 69(CCDC69)and breast cancer to analyze the effects of the differential expression of CCDC69 on the clinicopathology of breast cancer,and to study the mechanism of CCDC69 that affects prognosis in patients with breast cancer.Methods: We screened genes that were significantly differentially expressed between breast cancer and normal breast tissues by searching expression profile arrays of breast cancer in GEO datasets.Genes affecting the prognosis of patients with breast cancer were selected by Onco Lnc.Through literature review,we selected CCDC69 for further study.Similar genes whose correlation coefficients were greater than 0.8 with CCDC69 were detected in GEPIA.Enrichment analysis of CCDC69 and its similar genes was performed using Fun Rich 3.1.3 to explore the signal pathway by which CCDC69 affects breast cancer.Meanwhile,expressions of CCDC69 in breast cancer tissues and adjacent tissues of 24 patients with breast cancer were detected by quantitative real-time polymerase chain reaction(q RT-PCR).Immunohistochemistry was utilized to detect the expression of CCDC69 and a similar gene,SH3 domain-containing protein 1(SORBS1),in tumor tissues of patients with invasive breast cancer.We also explored the relationship between the differential expression of CCDC69 and the clinicopathology of breast cancer combined with clinical case information.Results: CCDC69 was screened under the condition of log2-fold change ≤-2 and P ≤ 0.05 in the GEO database.Our q RT-PCR detection confirmed that the expression of CCDC69 in breast cancer tissue was significantly lower than that in normal tissues(P=0.0002).The survival rate Kaplan plot showed that patients with breast cancer with lower expression of CCDC69 had a lower overall survival rate in Onco Lnc(Logrank P-value=0.000698).Through gene enrichment analysis,we found that CCDC69 and similar genes were significantly associated with fat differentiation.Moreover,most were related to the peroxisome proliferator-activated receptor(PPAR)signal pathway,and a large number of studies have confirmed that PPAR signal pathway was related to fat differentiation.Immunohistochemistry showed that the expression of CCDC69 was positively correlated with that of SORBS1(P =0.001),and it was negatively correlated with the expression of Ki67(P=0.001).An LSD multiple comparison showed that the positive expression rate of CCDC69 in triple negative breast cancer was significantly lower than that in Luminal A breast cancer and in HER2 breast cancer(P=0.014,0.034).The positive expression rate of CCDC69 in the triple negative breast cancer was lower than that in the non-triple-negative breast cancer(P=0.0362).Patients with triple negative breast cancer and Disease-Free survival(DFS)events exhibited lower levels of CCDC69 expression.Conclusion: Patients with lower expression of CCDC69 have stronger breast cancer cell proliferative ability,worse pathological types,and poorer clinical prognosis.CCDC69 may affect prognosis in patients with breast cancer by regulating the PPAR signal pathway,and may serve as a potential therapeutic target for patients with breast cancer.