Expression Of Reactive Oxygen Species Modulator 1 And Its Clinical Significance In Triple-Negative Breast Cancer

Purpose: Reactive Oxygen Species Modulator 1(ROMO1)is highly expressed in several malignancies.There have been many studies on its prognostic value in clinic,including in lung and liver cancer,but few in breast cancer.In this study,we investigated the relationship between ROMO1 and breast cancer through bioinformatics methods,detected the expression of ROMO1 in tumor tissues of triple-negative breast cancer(TNBC)patients by immunohistochemistry and analyzed its correlation with the clinicopathological characteristics.Methods: ROMO1 mRNA pan-cancer expression was analyzed by UALCAN platform.The correlation between ROMO1 mRNA expression levels and prognosis of TNBC patients was analyzed in GEPIA2 and KM-plotter platforms,respectively.The expression levels of ROMO1 in 60 TNBC tumor tissue and 15 adjacent normal tissue from Zhongda Hospital were detected by immunohistochemistry and scored semi-quantitatively.The differential expression of ROMO1 in tumor tissues compared with adjacent noncancerous tissues was analyzed by Mann-Whitney test.The relationship between different ROMO1 expression levels in tumor tissues and clinical characteristics of patients,such as age,lymph node status,histological grade,and Ki67 status,was compared by rank sum test or chi-square test.Logistic regression was used to analyze the risk factors for lymph node metastasis.The Kaplan-Meier method was used to depict the survival curves.For the relevant regulatory pathways that ROMO1 may be involved in,bioinformatic prediction of mi RNAs upstream of ROMO1 mRNA was performed using Target Scan.STRING was used to predict ROMO1 protein interactions with other proteins.Data were statistically analyzed and plotted by SPSS18.0 and Graph Pad prism 8.4.3.Results: 1.Analysis of public databases showed that ROMO1 mRNA was highly expressed in several malignant tumors including breast cancer(P<0.001).2.In the GEPIA2 database,no significant correlation was observed between ROMO1 expression levels and prognosis in TNBC patients(P>0.05).3.In the KM-plotter database,compared to the low-expression group,the DFS was shorter in the ROMO1 high-expression group(P=0.021),and the difference in OS was not statistically significant(P=0.19).4.Immunohistochemistry results showed that ROMO1 was highly expressed in breast cancer tissues from TNBC patients compared to adjacent tissues(P<0.001).5.Statistically significant differences(P<0.05)were found between the high and low ROMO1 expression groups in terms of TNBC lymph node metastasis and systemic immune-inflammation index,and no significant correlation was observed with patient’s age,tumor diameter,Ki67,or vasculature tumor thrombus.6.After univariate and multifactorial analyses,tumor diameter,choroidal carcinoma thrombus,and ROMO1 expression were independent predictors of lymph node metastasis in TNBC patients(P<0.05).7.No correlation between ROMO1 protein expression level and prognosis of TNBC patients was observed in this study.8.ROMO1 mRNA expression may be regulated by mi R-18a-5p,mi R-18b-5p and mi R-4735-3p.ROMO1 protein may interact with TCEB2,UQCR11,NDUFB7,NDUFA2,ATP5 I,TIMM50,TIMM23,TIMM17 B,TIMM17A,and TIMM21.Conclusion: ROMO1 mRNA and protein are highly expressed in breast cancer tissues.In TNBC,patients with high expression of ROMO1 are more likely to present axillary lymph node metastasis,with the increased level of inflammation.The high expression of ROMO1 is an independent risk factor for TNBC lymph node metastasis.The prognostic value of ROMO1 in TNBC still needs further study.