# In Silico Transcriptomic Analysis for Identification of Potential Diagnostic and Prognostic Biomarkers and Therapeutic Targets in Cervical Cancer using a Hybrid Genetic Algorithm–Support Vector Machine Approach

**Authors:** Leila Nezamabadi Farahani, Anoshirvan Kazemnejad, Mahlagha Afrasiabi, Leili Tapak

PMC · DOI: 10.34172/aim.34814 · 2025-12-01

## TL;DR

This study uses machine learning to find genes that could help diagnose, predict outcomes, and treat cervical cancer based on transcriptomic data.

## Contribution

A hybrid GA-SVM approach identifies novel diagnostic, prognostic, and therapeutic gene signatures in cervical cancer.

## Key findings

- Eight genes (CXCL9, CTGF, ZNF704, ZEB2, SASH1, PTN, KPNA2, SLC5A1) were identified as diagnostic biomarkers.
- 42 therapeutic targets linked to cell cycle, DNA repair, and mitotic processes were found.
- Six genes (CXCL1, DNMT1, MMP1, MYBL2, PCNA, RRM2) were identified as key prognostic markers.

## Abstract

Cervical cancer is the leading malignancy among women worldwide, posing clinical and public health challenges. This in silico study aims to identify potential diagnostic biomarkers, therapeutic targets, and prognostic markers associated with cervical cancer through integrative bioinformatics approaches.

A hybrid machine learning approach, combining genetic algorithm (GA) and support vector machine (SVM), was applied to high-dimensional gene expression data from publicly available transcriptomic datasets, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A total of 72 Geo samples (Affymetrix, Illumina) served as the primary dataset after normalization.

The GA-SVM model achieved about 99% accuracy and AUC with 10-fold cross validation, clearly separating cervical cancer from normal tissues. Eight genes (CXCL9, CTGF, ZNF704, ZEB2, SASH1, PTN, KPNA2, SLC5A1) were identified as diagnostic biomarkers. Protein-protein interaction (PPI) and functional enrichment analyses revealed 42 therapeutic targets (e.g. CDK1, BRCA1, CCNB1, and AURKB) linked to regulating cell cycle, DNA repair, and mitotic processes. Survival analysis identified six genes (CXCL1, DNMT1, MMP1, MYBL2, PCNA, and RRM2) as key prognostic markers. Additionally, transcription factor analysis identified E2F1 and TP63 as major regulators of the prognostic genes, elucidating the molecular mechanisms underlying cervical cancer progression.

The identified gene signatures may serve as candidates for hypothesis generation and provide a computational framework to prioritize biomarkers and therapeutic targets in cervical cancer. However, these findings are based on in silico analyses and require experimental and clinical validation before translation into practice.

## Linked entities

- **Genes:** CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283], CCN2 (cellular communication network factor 2) [NCBI Gene 1490], ZNF704 (zinc finger protein 704) [NCBI Gene 619279], ZEB2 (zinc finger E-box binding homeobox 2) [NCBI Gene 9839], SASH1 (SAM and SH3 domain containing 1) [NCBI Gene 23328], PTN (pleiotrophin) [NCBI Gene 5764], KPNA2 (karyopherin subunit alpha 2) [NCBI Gene 3838], SLC5A1 (solute carrier family 5 member 1) [NCBI Gene 6523], CDK1 (cyclin dependent kinase 1) [NCBI Gene 983], BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672], CCNB1 (cyclin B1) [NCBI Gene 891], AURKB (aurora kinase B) [NCBI Gene 9212], CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919], DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786], MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312], MYBL2 (MYB proto-oncogene like 2) [NCBI Gene 4605], PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111], RRM2 (ribonucleotide reductase regulatory subunit M2) [NCBI Gene 6241], E2F1 (E2F transcription factor 1) [NCBI Gene 1869], TP63 (tumor protein p63) [NCBI Gene 8626]
- **Diseases:** cervical cancer (MONDO:0002974)

## Full-text entities

- **Genes:** PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, AURKB (aurora kinase B) [NCBI Gene 9212] {aka AIK2, AIM-1, AIM1, ARK-2, ARK2, AurB}, TOP2A (DNA topoisomerase II alpha) [NCBI Gene 7153] {aka TOP2, TOP2alpha, TOPIIA, TP2A}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, TP63 (tumor protein p63) [NCBI Gene 8626] {aka AIS, B(p51A), B(p51B), EEC3, KET, LMS}, KPNA2 (karyopherin subunit alpha 2) [NCBI Gene 3838] {aka IPOA1, PTAC58, QIP2, RCH1, SRP1-alpha, SRP1alpha}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, EP300 (EP300 lysine acetyltransferase) [NCBI Gene 2033] {aka KAT3B, MKHK2, RSTS2, p300}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, BACH1 (BTB domain and CNC homolog 1) [NCBI Gene 571] {aka BACH-1, BTBD24}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, CDK1 (cyclin dependent kinase 1) [NCBI Gene 983] {aka CDC2, CDC28A, P34CDC2}, E2F1 (E2F transcription factor 1) [NCBI Gene 1869] {aka E2F-1, RBAP1, RBBP3, RBP3}, MYBL2 (MYB proto-oncogene like 2) [NCBI Gene 4605] {aka B-MYB, BMYB}, CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919] {aka FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3}, MELK (maternal embryonic leucine zipper kinase) [NCBI Gene 9833] {aka HPK38}, SASH1 (SAM and SH3 domain containing 1) [NCBI Gene 23328] {aka CAPOK, DUH, DUH1, SH3D6A, dJ323M4.1}, AURKA (aurora kinase A) [NCBI Gene 6790] {aka AIK, ARK1, AURA, BTAK, PPP1R47, STK15}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, ZEB2 (zinc finger E-box binding homeobox 2) [NCBI Gene 9839] {aka HSPC082, SIP-1, SIP1, SMADIP1, ZFHX1B}, KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, BUB1 (BUB1 mitotic checkpoint serine/threonine kinase) [NCBI Gene 699] {aka BUB1A, BUB1L, MCPH30, hBUB1}, BIRC5 (baculoviral IAP repeat containing 5) [NCBI Gene 332] {aka API4, EPR-1}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, FOXA1 (forkhead box A1) [NCBI Gene 3169] {aka HNF3A, TCF3A}, PTN (pleiotrophin) [NCBI Gene 5764] {aka HARP, HB-GAM, HBBM, HBGF-8, HBGF8, HBNF}, RAD51 (RAD51 recombinase) [NCBI Gene 5888] {aka BRCC5, FANCR, HRAD51, HsRad51, HsT16930, MRMV2}, RRM2 (ribonucleotide reductase regulatory subunit M2) [NCBI Gene 6241] {aka C2orf48, R2, RR2, RR2M}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, LGALS1 (galectin 1) [NCBI Gene 3956] {aka GAL1, GBP}, SLC5A1 (solute carrier family 5 member 1) [NCBI Gene 6523] {aka D22S675, NAGT, SGLT-1, SGLT1}, CHEK1 (checkpoint kinase 1) [NCBI Gene 1111] {aka CHK1, OZEMA21}, ZNF704 (zinc finger protein 704) [NCBI Gene 619279] {aka Gig1}, CCNB1 (cyclin B1) [NCBI Gene 891] {aka CCNB}
- **Diseases:** endocervical adenocarcinoma (MESH:D000230), lymph node metastasis (MESH:D008207), HPV infection (MESH:D030361), Cervical Cancer (MESH:D002583), infection (MESH:D007239), invasive cancers (MESH:D009362), cervical squamous cell carcinoma (MESH:D002294), cervical intraepithelial neoplasia (MESH:D002578), Cancer (MESH:D009369)
- **Species:** Human papillomavirus 16 (serotype) [taxon 333760], Homo sapiens (human, species) [taxon 9606], Halorubrum sp. PV6 (species) [taxon 634157], Human papillomavirus (species) [taxon 10566], human papillomavirus 11 (serotype) [taxon 10580]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13000335/full.md

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Source: https://tomesphere.com/paper/PMC13000335