# Gene Mutations and Related Molecular Events in Distant Metastasis of Cervical Cancer: A Review

**Authors:** Yinghua Guo, Shilong Li, Tingting Liu, Xiaolong Chang, Peiyan Qin, Nan Wang, Yingxiao Jiang, Na Lv, Niannian Li, Furong Hao

PMC · DOI: 10.7150/ijms.123727 · 2026-02-11

## TL;DR

This paper reviews how specific gene mutations contribute to cervical cancer metastasis and how detecting them can improve diagnosis and treatment.

## Contribution

The study highlights PDGFRA, TP53, and PIK3CA mutations as key drivers of cervical cancer metastasis and their diagnostic and therapeutic implications.

## Key findings

- PDGFRA mutations are closely linked to lymph node and distant metastasis in cervical cancer.
- TP53 mutations disrupt p53 function, promoting tumor growth and metastasis.
- PIK3CA mutations activate the PI3K/Akt pathway, enhancing cell proliferation and migration.

## Abstract

Cervical cancer, a serious gynecological malignancy, often leads to poor patient prognosis due to distant metastasis. The metastasis mechanism is not fully understood. This study explores the link between gene mutations and distant metastasis in cervical cancer. PDGFRA, TP53, and PIK3CA mutations significantly influence metastasis. Despite its low incidence, PDGFRA mutation is closely tied to lymph node and distant metastasis. TP53 mutation disrupts p53 protein function, promoting tumor cell proliferation, inhibiting apoptosis, and enhancing metastasis. PIK3CA mutation activates the PI3K/Akt pathway, stimulating cell proliferation and migration. Detecting these mutations is crucial for diagnosing distant metastasis. It helps identify high-risk patients early, improving diagnostic accuracy and specificity, and guiding clinical treatment decisions. Targeted therapies for PDGFRA and PIK3CA mutations can control tumor growth and metastasis but face challenges like drug resistance and high costs. This study offers a new theoretical basis and treatment strategy for cervical cancer, pointing to future research directions. Gene mutation detection enhances early identification of high-risk patients, improving diagnostic accuracy. Targeted therapies for PDGFRA and PIK3CA mutations control tumor growth but face drug resistance and cost issues. This study provides a new theoretical basis and treatment strategy for cervical cancer, guiding future research.

## Linked entities

- **Genes:** PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156], TP53 (tumor protein p53) [NCBI Gene 7157], PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290]
- **Proteins:** TP53 (tumor protein p53)
- **Diseases:** cervical cancer (MONDO:0002974)

## Full-text entities

- **Genes:** ZEB1 (zinc finger E-box binding homeobox 1) [NCBI Gene 6935] {aka AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3}, Mir21a (microRNA 21a) [NCBI Gene 387140] {aka Mir21, Mirn21, mmu-mir-21, mmu-mir-21a}, RB1 (RB transcriptional corepressor 1) [NCBI Gene 5925] {aka OSRC, PPP1R130, RB, p105-Rb, p110-RB1, pRb}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, VIM (vimentin) [NCBI Gene 7431], Pten (phosphatase and tensin homolog) [NCBI Gene 19211] {aka 2310035O07Rik, A130070J02Rik, B430203M17Rik, MMAC1, PTENbeta, TEP1}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, ATR (ATR checkpoint kinase) [NCBI Gene 545] {aka FCTCS, FRP1, MEC1, SCKL, SCKL1}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TWIST1 (twist family bHLH transcription factor 1) [NCBI Gene 7291] {aka ACS3, BPES2, BPES3, CRS, CRS1, CSO}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, Pik3ca (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 18706] {aka 6330412C24Rik, caPI3K, p110, p110alpha}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, Trp53 (transformation related protein 53) [NCBI Gene 22059] {aka Tp53, bbl, bfy, bhy, p44, p53}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156] {aka CD140A, PDGFR-2, PDGFR2}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}
- **Diseases:** visual impairment (MESH:D014786), hematuria (MESH:D006417), CC (MESH:D002583), bone pain (MESH:D010146), fractures (MESH:D050723), headaches (MESH:D006261), benign diseases (MESH:D004194), hyperglycemia (MESH:D006943), undifferentiated carcinoma (MESH:D002277), limb edema (MESH:D004487), dyspnea (MESH:D004417), adenocarcinoma (MESH:D000230), malignancy (MESH:D009369), chest pain (MESH:D002637), jaundice (MESH:D007565), hemoptysis (MESH:D006469), tumorigenesis (MESH:D063646), rash (MESH:D005076), bleeding (MESH:D006470), cervical squamous cell carcinoma (MESH:D002294), vomiting (MESH:D014839), genetic abnormalities (MESH:D030342), spinal cord compression (MESH:D013117), endometritis (MESH:D004716), deaths (MESH:D003643), ascites (MESH:D001201), gastrointestinal stromal tumors (MESH:D046152), Hematogenous metastasis (MESH:D009362), pyometra (MESH:D055112), coughing (MESH:D003371), dizziness (MESH:D004244), gynecological malignancy (MESH:D005833), abnormal liver function (MESH:D056486), liver pain (MESH:D017093), constipation (MESH:D003248), hemiplegia (MESH:D006429), lymph node (MESH:D000072717), breast cancer (MESH:D001943), Lymphatic metastasis (MESH:D008207)
- **Chemicals:** phosphatidylinositol (MESH:D010716), GTP (MESH:D006160), platinum (MESH:D010984), Alpelisib (MESH:C585539), PIP2 (MESH:D019269), Imatinib (MESH:D000068877), trametinib (MESH:C560077), sunitinib (MESH:D000077210), BKM120 (MESH:C571178), GDP (MESH:D006153), PIP3 (-), cisplatin (MESH:D002945), disulfiram (MESH:D004221), phosphatidylinositol-3,4,5-triphosphate (MESH:C060974), gefitinib (MESH:D000077156), lipid (MESH:D008055), ATP (MESH:D000255)
- **Species:** Human papillomavirus (species) [taxon 10566], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Human papillomavirus 16 (serotype) [taxon 333760]
- **Mutations:** E545K, H1047R, L858R, V600E, G13V, D842V, G12D, E542K

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12964585/full.md

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Source: https://tomesphere.com/paper/PMC12964585