# Scrutinizing the potential role of non-coding RNAs as biomarkers in Egyptian females with early and metastatic breast cancer

**Authors:** Eman ElAlfy, Nourhan E Gaber, Madiha H Helmy, Maher A Kamel, Sara A Shaker

PMC · DOI: 10.1186/s12885-025-15483-0 · BMC Cancer · 2026-01-14

## TL;DR

This study explores non-coding RNAs as potential biomarkers for early detection and prognosis of breast cancer in Egyptian women.

## Contribution

The study identifies specific non-coding RNAs that may serve as better biomarkers than traditional markers in breast cancer.

## Key findings

- Circulating ncRNAs distinguished early breast cancer patients from healthy controls better than CEA and CA15-3.
- PVT1, HOTAIR, miR-331, and miR-195 showed potential as diagnostic and prognostic biomarkers.
- Validation in larger cohorts is needed for clinical application.

## Abstract

Breast cancer (BC) is the second most frequently diagnosed malignancy worldwide and the most common cancer among Egyptian women, accounting for 38.8% of female malignancies. Early diagnosis is critical for improving outcomes; however, conventional serum tumor markers such as CEA and CA15-3 show limited sensitivity and specificity in early-stage BC. Liquid biopsy has emerged as a promising non-invasive approach, enabling detection of circulating tumor-derived products, including non-coding RNAs (ncRNAs). This study aimed to evaluate the differential expression of circulating ncRNAs in the serum of female patients with early and metastatic BC prior to initiation of chemotherapy, and to assess their associations with clinicopathological characteristics and prognostic parameters. We also sought to determine their potential utility as prognostic biomarkers for early detection of metastasis. Method: A total of fifty female participants were enrolled following ethical approval and categorized into three groups: healthy controls (n = 10), early-stage breast cancer patients (n = 21), and metastatic breast cancer patients (n = 19). All breast cancer cases were diagnosed with invasive disease and exhibited mixed hormone receptor status. Result: the results demonstrated that the studied ncRNAs (miRNAs and lncRNAs) effectively distinguished early BC patients from healthy controls, whereas CEA and CA15-3 did not. Conclusion: This pilot study provides preliminary evidence that PVT1, HOTAIR, miR-331, and miR-195 may represent potential diagnostic and prognostic biomarkers in BC. However, due to the limited sample size and exploratory nature of the analyses, validation in larger, independent, and prospectively collected cohorts is essential before clinical application can be established.

## Linked entities

- **Genes:** PVT1 (Pvt1 oncogene) [NCBI Gene 5820], HOTAIR (HOX transcript antisense RNA) [NCBI Gene 100124700], MIR331 (microRNA 331) [NCBI Gene 442903], MIR195 (microRNA 195) [NCBI Gene 406971]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31] {aka ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, HOTAIR (HOX transcript antisense RNA) [NCBI Gene 100124700] {aka HOXAS, HOXC-AS4, HOXC11-AS1, NCRNA00072}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, CCNE1 (cyclin E1) [NCBI Gene 898] {aka CCNE, pCCNE1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164] {aka GFRP1, HMR, N10, NAK-1, NGFIB, NP10}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, PVT1 (Pvt1 oncogene) [NCBI Gene 5820] {aka LINC00079, MIR1204HG, NCRNA00079, TP53LC09, onco-lncRNA-100}, CDK6 (cyclin dependent kinase 6) [NCBI Gene 1021] {aka MCPH12, PLSTIRE}, CYP27B1 (cytochrome P450 family 27 subfamily B member 1) [NCBI Gene 1594] {aka CP2B, CYP1, CYP1alpha, CYP27B, P450c1, PDDR}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, PPRC1 (PPARG related coactivator 1) [NCBI Gene 23082] {aka PRC}, MIR195 (microRNA 195) [NCBI Gene 406971] {aka MIRN195, miRNA195, mir-195}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) [NCBI Gene 3156] {aka LDLCQ3, LGMDR28, MYPLG}, MIR331 (microRNA 331) [NCBI Gene 442903] {aka MIRN331, hsa-mir-331, mir-331}, NcRNA [NCBI Gene 54719], IRF1 (interferon regulatory factor 1) [NCBI Gene 3659] {aka IMD117, IRF-1, MAR}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, CDK4 (cyclin dependent kinase 4) [NCBI Gene 1019] {aka CMM3, MCPH31, PSK-J3}
- **Diseases:** liver cirrhosis (MESH:D008103), fibroadenoma (MESH:D018226), gastric cancer (MESH:D013274), adenocarcinoma of prostate (MESH:D000230), luminal A and B. (MESH:D006509), invasive (MESH:D009361), ovarian cancer (MESH:D010051), hepatocellular carcinoma (MESH:D006528), Tumor (MESH:D009369), head and neck squamous cell carcinoma (MESH:D000077195), hypertension (MESH:D006973), glioblastoma (MESH:D005909), non-small-cell lung cancer (MESH:D002289), lymph node metastases (MESH:D008207), infection (MESH:D007239), osteosarcoma (MESH:D012516), pancreatic cancer (MESH:D010190), PV (MESH:D011087), Metastatic (MESH:D000092182), Cardiac Carcinoma (MESH:D006338), BC cell malignancy (MESH:D001943), tumorigenesis (MESH:D063646), gastrointestinal cancer (MESH:D005770), autoimmune, inflammatory, or chronic systemic diseases (MESH:D019693), colorectal cancer (MESH:D015179), breast fibroma (MESH:D061325), cervical cancer (MESH:D002583), female (MESH:D005831), diabetes mellitus (MESH:D003920), bone metastasis (MESH:D009362), cholangiocarcinoma (MESH:D018281)
- **Chemicals:** Taxol (MESH:D017239), Adriamycin (MESH:D004317), CA15.5 (-), Cyclophosphamide (MESH:D003520), water (MESH:D014867), SYBR Green (MESH:C098022), methotrexate (MESH:D008727)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs13281615, AUC of 0
- **Cell lines:** MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), NR_047517.1 — Homo sapiens (Human), Nasopharyngeal carcinoma, Cancer cell line (CVCL_DG72), Hs578t — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0332), NR_003367.3 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_6691)

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## Figures

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## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC12836842/full.md

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Source: https://tomesphere.com/paper/PMC12836842