MicroRNA-124-3p Functions as a Marker in Diagnosing Breast Cancer


 BackgroundEarly diagnosis of breast cancer can reduce the high fatality rate. Thus novel diagnostic methods are urgently required for breast cancer patients. The research aimed at checking potential correlation for serum microRNA-124-3p (miR-124-3p) expression with breast cancer, and exploring its competence as a promising potential biomarkers for breast cancer.MethodsQuantitative real-time PCR (qRT-PCR) assay detected miR-124-3p levels. Possible relationship between miR-124-3p degree and clinical features of breast cancer patients was measured by Chi-square analysis. Sensitivity, specificity and area under the curve (AUC) for serum miR-124-3p degree were settled adopting receiver operating characteristics (ROC) analyses.ResultsRelative degree for serum miR-124-3p notably reduced among breast cancer sufferers in comparison with healthy persons (P=0.000). Moreover, miR-124-3p degree held tight connection to clinical stage (P=0.034), histological grade (P=0.002), and lymph node metastasis (P=0.001). ROC curve analyses unveiled at the optimal cut-off of 0.935, serum miR-124-3p expression reached a sensitivity of 78.4% and a specificity of 84.8% in discriminating between breast cancers sufferers and healthy persons, achieving an area under the curve (AUC) of 0.872 (95% CI: 0.752-0.871).ConclusionSerum miR-124-3p degree might represent one non-invasive indicator in diagnosing breast cancer.

optimal cut-off of 0.935, serum miR-124-3p expression reached a sensitivity of 78.4% and a speci city of 84.8% in discriminating between breast cancers sufferers and healthy persons, achieving an area under the curve (AUC) of 0.872 (95% CI: 0.752-0.871).

Conclusion
Serum miR-124-3p degree might represent one non-invasive indicator in diagnosing breast cancer.

Background
Breast cancer represents one most widespread malignancy among females around the world [1]. The incidence of breast cancer varies across the world, usually lower in less-developed countries than that in the more-developed countries. It is of great importance for early detection together with curative resection to improve breast cancer prognoses [2,3]. Currently, the pathological observation are the main approaches to diagnose this disease. With considerable advancements in identifying serum indicators, it is essentially required to nd indicators holding satisfactory speci city and sensitivity through serum detection, which is bene cial for precise screening, target treatment and outcome prediction [4]. Until now, no satisfactory indicators have been established in screening the malignancy. Hence, nding promising novel indicators would held considerable clinical signi cance.
Through the present research, we detected relative degree for serum miR-124-3p in breast cancer, and evaluated possible connection for serum miR-124-3p to clinicopathological characteristics among cases with breast cancers. We also assessed the diagnostic performance of serum miR-124-3p in breast cancer.

Methods And Materials
Patients and serum samples Our research acquired permission from the Ethic Committee of the 903rd Hospital of PLA. Enrolled subjects signed the informed consents.
Serum specimens came from 105 breast cancer sufferers receiving treatments in the 903rd Hospital of PLA. Histopathology for cases was examined. Cases would be removed from our study once they had other cancers at any sites or experienced chemotherapy or radiotherapy ahead of sampling. Detailed clinicopathological indexes for cases were manifested by Table 1. 97 normal serum samples from healthy volunteers was recruited as controls.

Results
Serum miR-124-3p expression among breast cancer and healthy controls As shown in Figure 1, qRT-PCR revealed serum miR-124-3p level strongly lowered among breast cancer sufferers in comparison to healthy persons (0.669±0.296 vs 1.130±0.434). The median miR-124-3p degree among all 105 patients with breast cancer was 0.64. We classi ed enrolled cases into low (n=54) and high (n=51) miR-124-3p level classes using the median degree as a cutoff.
Correlation for serum miR-124-3p degree with clinicopathological traits among sufferers with breast cancer According to the results of Chi-square test, serum miR-124-3p degree exhibited strong connection to clinical stage (P=0.034), histological grade (P=0.002), and lymph node metastasis (P=0.001), but not to age, cancer dimension, ER, PR, or HER-2 (all P>0.05).
Diagnostic e cacy for serum miR-124-3p in breast cancers ROC curves was plotted to identify whether miR-124-3p could discriminate between breast cancer sufferers and healthy persons. The results unveiled at the optimal cut-off (0.935), serum level of miR-124-3p achieved a sensitivity of 78.4% and a speci city of 84.8% to discriminate the cases and controls, reaching an area under the curve AUC of 0.872 (95% CI: 0.752-0.871, Figure 2).

Discussion
Over the decades, survivals for breast cancer sufferers at early stages are lengthened [21]. Apart from timely diagnosis, adjuvant chemotherapy and endocrine therapy also considerably better cases' overall survivals. There are two traditional indicators in diagnosing this malignancy, CA15.3 and CEA, and the previous studies have demonstrated sensitivity and speci city for them lie at 15-45% and 10-30%, separately. They are unsatisfactory for screening of breast cancer. Recently, miR-124-3p was reported to be generally reduced in multiple tumors while its transfection suppresses the malignant cellular growth and migration [22][23][24][25]. For example, Gov E et al. reported that miR-124-3p was a plausible indicator in ovarian cancer [22]. Yuan and colleagues demonstrated miR-124-3p expression down-regulated amid bladder cancer tissues and cell lines, which played important role on malignant cellular multiplication, emigration and apoptosis [23]. Moreover, in the study of Margolin-Miller Y and colleagues, high miR-124-3p degree held strong connection to shortened progression-free survivals among ependymoma patients, which might represent a self-su cient indicator for prognoses in this disease [24]. Zhang and colleagues claimed miR-124-3p declined among breast cancer tissues and breast cell lines. Its declines promoted malignant cellular advancement primarily through elevating degree for autophapy relevant protein, Beclin-1 [25].
Currently, explorations on indicators wield essential functions in comprehending mechanisms for varied illnesses. Despite their employment in diagnosing breast cancer, CEA and CA15.3 merely possess insu cient sensitivity and speci city, especially for cases at early stages. MicroRNAs could generate pivotal in uences on tumorigenesis. It has been revealed half of them seat at tumour-relevant genomic positions/fragile loci, which indicated their involvement in tumour origination and development [26].
Currently, miRNAs have great potential as novel biomarkers in diagnosing, therapeutic monitor, and predicting outcomes among breast cancer sufferers.
In this research, serum miR-124-3p degree dramatically reduced among breast cancer sufferers in comparison to controls. Moreover, we found that serum miR-124-3p degree possessed tight connection to clinical stage, histological grade, and lymph node metastasis, suggesting its involvement in breast cancer advancement and metastasis. Our ndings were consistent with the previous studies [25]. ROC curve analyses con rmed serum miR-124-3p degree had a high sensitivity and speci city in discriminating between breast cancer sufferers and healthy persons, reaching high AUC values.
Multiple shortcomings of this research should be noted. Firstly, miR-124-3p might assume repressing effects against breast cancer, but potential mechanisms for such activities remained unknown. Future experiments are still necessary to ascertain unspeci ed in uences for miR-124-3p and its aims in the malignancy onset and development. Another limitation is the relatively small size. Larger-scale researches would be indispensable to con rm e cacy for serum miR-124-3p expression to diagnose breast cancer for making more de nitive conclusions.

Conclusion
Taken together, serum miR-124-3p expression dramatically decreased among breast cancer sufferers in comparison to healthy persons. Low miR-124-3p degree exhibited strong connection to the cancer development and progression. Our ndings offered primary evidence of miR-124-3p affecting breast cancer and its potential to be adopted in early diagnosing this malignancy. The subjects had been informed the objective. Certainly, written consents were signed by every subject in this study.

Consent for publication
We obtaining permission from participants to publish their data.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.  Serum miR-124-3p expression level in breast cancer patients and healthy controls. Serum expression level of miR-124-3p in patients with breast cancer was signi cantly lower than healthy controls (P=0.000).