Expression of human endogenous retrovirus subfamily H long terminal repeat associating protein 2 in osteosarcoma and its clinical significance
Objective To investigate the expression of human endogenous retrovirus subfamily H long terminal repeat associating protein 2(HHLA2)in osteosarcoma and its clinical significance.Methods 99 cases of osteosarcoma and adjacent tissues resected in Zhengzhou orthopedic hospital from January 2023 to June 2024 were selected as the research objects.The protein and mRNA expression levels of HHLA2 were analyzed by Western blotting and fluorescence quantitative PCR.The protein expression levels of Ja-nus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)were analyzed by im-munohistochemistry.The correlation between HHLA2 expression level and JAK2-STAT3 expression was an-alyzed.The relationship between HHLA2 and the clinicopathological characteristics and prognosis of osteo-sarcoma patients was analyzed.Multivariate regression analysis was used to analyze the main factors affect-ing the prognosis of patients with osteosarcoma.The measurement data between groups were compared by independent sample t test.Results The expression levels of HHLA2 mRNA and protein in adjacent tis-sues(0.84±0.20,0.86±0.21)were significantly lower than those in osteosarcoma tissues(1.78±0.21,1.63±0.24,t=32.190,24.110,P<0.05).The positive rate of JAK2 expression and STAT3 ex-pression in osteosarcoma tissues was 59.60%(59/99)and 75.76%(75/99).The expression level of HHLA2 protein in osteosarcoma tissues was correlated with the positive rates of JAK2 and STAT3 expres-sion(r=1.298,2.014,P<0.05).There was no significant difference in the expression level of HHLA2 protein in osteosarcoma tissues between chondroblastoma and osteoblastoma patients(1.60±0.29,1.65±0.21,t=0.938,P>0.05).The expression level of HHLA2 protein in osteosarcoma tissues of stageⅠ-Ⅱ patients(1.49±0.14)was significantly lower than that of stage Ⅲ patients(1.85±0.19,t=11.060,P<0.05).The expression level of HHLA2 protein in osteosarcoma tissues of patients without lymph node metastasis(1.51±0.19)was significantly lower than that of patients with lymph node metasta-sis(1.83±0.17,t=8.602,P<0.05).The expression level of HHLA2 protein in osteosarcoma tissues of patients with medium to high differentiation(1.72±0.21)was significantly lower than that in patients with lymph node metastasis(1.54±0.24,t=4.129,P<0.05).There were 41 patients in the poor prognosis group,accounting for 41.41%;58 cases(58.59%)in the good prognosis group.The protein expression level of HHLA2 in osteosarcoma tissues of patients with poor prognosis(1.76±0.19)was significantly low-er than that of patients with good prognosis(1.54±0.23,t=4.852,P<0.05).The area under the curve of hhla2 expression in osteosarcoma tissues was 0.890.The standard deviation was 0.045,and the 95%confidence interval(CI)was 0.767-0.948(P<0.05).The sensitivity,specificity and accuracy of diagnosis were 84.69%,85.89%and 78.95%,respectively.High Eneeking stage,distal metastasis and high HHLA2 level were the main risk factors for death in patients with osteosarcoma(P<0.05).Conclusion HHLA2 is highly expressed in osteosarcoma tissues and is closely related to JAK2-STAT3 signaling pathway.The expression levels of HHLA2,JAK2 and STAT3 can be used as auxiliary diagnostic markers for the clinical malignant pathological characteristics and prognosis of osteosarcoma.
OsteosarcomaEndogenous retrovirus-h long terminal repeat associated protein 2Clinicopathological featuresPrognosisJanus kinase 2-signal transducer and activator of transcription 3 signaling pathway