# APOs as promising prognostic biomarkers: correlation with tumor-infiltrating leukocytes in endometrial cancer

**Authors:** Lina Zhou, Rencheng Wang, Guiqiang Du, Yupeng Wu, Hui Li, Yinyan He, Zhikang Ye, Jiangdong Xiang

PMC · DOI: 10.3389/fimmu.2026.1646920 · Frontiers in Immunology · 2026-02-16

## TL;DR

This study explores apolipoproteins (APOs) as potential biomarkers for endometrial cancer prognosis and their link to immune cell infiltration.

## Contribution

The study identifies specific APO genes correlated with survival and immune infiltration in endometrial cancer patients.

## Key findings

- Nine APO genes showed differential expression in endometrial cancer tissues compared to controls.
- APOD and APOE expression levels correlated with tumor-infiltrating leukocytes and patient survival.
- APOE promotes cell migration in endometrial cancer cells in vitro.

## Abstract

Apolipoproteins (APOs) are essentially structural and functional components of lipoproteins, which are composed of 22 members and their effects on certain types of cancer have been studied. However, their roles in endometrial cancer (EC), which is one of the most common malignant tumors in gynecology were unclear and rarely investigated.

We investigated the expression levels of APOs genes in EC. Furthermore, we explored the roles of APOs in prognostic value, and immune infiltrates in EC patients by using different bioinformatics databases. In-vitro experiments were also conducted to evaluate the effect of APOs genes expression on migrant abilities of EC cells.

Nine APO genes (APOC1, APOC2, APOC4, APOD, APOE, APOL3, APOL4, APOLD1, and APOO) were found differently expressed between EC and control tissues by the GEPIA2. However, APOC4 was not included in the subsequent analysis due to its low expression in EC tissues. Moreover, mRNA expression levels of APOs were found correlated with the clinicopathological characteristics of EC, including stage, grade, molecular subgroups, p53 mutant conditions, PTEN mutant conditions, and expression levels of ESR1 and ESR2. Meanwhile higher expression levels of APOs were significantly correlated with better (APOD, APOL3) or poorer (APOC1, APOE, APOLD1) OS. ssGSEA showed 7 TILs in EC which differed significantly from those in adjacent noncancerous tissues were correlated with prognosis of EC patients. The expression levels of both APOD and APOE were positively correlated with all 7 TILs. Finally, western blotting showed that 17β-estradiol (E2) increased APOE protein expression level and reduced APOD protein expression level. Furthermore, APOE was identified to promote the cell migration by scratch assay.

The expression of APOs may be a promising prognostic biomarker and is associated with immune invasion as a potential target for endometrial cancer.

## Linked entities

- **Genes:** APOC1 (apolipoprotein C1) [NCBI Gene 341], APOC2 (apolipoprotein C2) [NCBI Gene 344], APOC4 (apolipoprotein C4) [NCBI Gene 346], APOD (apolipoprotein D) [NCBI Gene 347], APOE (apolipoprotein E) [NCBI Gene 348], APOL3 (apolipoprotein L3) [NCBI Gene 80833], APOL4 (apolipoprotein L4) [NCBI Gene 80832], APOLD1 (apolipoprotein L domain containing 1) [NCBI Gene 81575], APOO (apolipoprotein O) [NCBI Gene 79135], TP53 (tumor protein p53) [NCBI Gene 7157], PTEN (phosphatase and tensin homolog) [NCBI Gene 5728], ESR1 (estrogen receptor 1) [NCBI Gene 2099], ESR2 (estrogen receptor 2) [NCBI Gene 2100]
- **Proteins:** APOE (apolipoprotein E), APOD (apolipoprotein D)
- **Chemicals:** 17β-estradiol (PubChem CID 154274)
- **Diseases:** endometrial cancer (MONDO:0002447)

## Full-text entities

- **Genes:** APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, APOC3 (apolipoprotein C3) [NCBI Gene 345] {aka APOCIII, Apo-C3, ApoC-3}, BLNK (B cell linker) [NCBI Gene 29760] {aka AGM4, BASH, BLNK-S, LY57, SLP-65, SLP65}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, CD226 (CD226 molecule) [NCBI Gene 10666] {aka DNAM-1, DNAM1, PTA1, TLiSA1}, APOD (apolipoprotein D) [NCBI Gene 347], ESR2 (estrogen receptor 2) [NCBI Gene 2100] {aka ER-BETA, ESR-BETA, ESRB, ESTRB, Erb, NR3A2}, APOA2 (apolipoprotein A2) [NCBI Gene 336] {aka APOA2D, Apo-AII, ApoA-II, apoAII}, APOL4 (apolipoprotein L4) [NCBI Gene 80832] {aka APOL-IV, APOLIV}, APOC2 (apolipoprotein C2) [NCBI Gene 344] {aka APO-CII, APOC-II}, APOL2 (apolipoprotein L2) [NCBI Gene 23780] {aka APOL-II}, PVR (PVR cell adhesion molecule) [NCBI Gene 5817] {aka CD155, HVED, NECL5, Necl-5, PVS, TAGE4}, APOL6 (apolipoprotein L6) [NCBI Gene 80830] {aka APOL-VI, APOLVI}, APOH (apolipoprotein H) [NCBI Gene 350] {aka B2G1, B2GP1, BG}, GPER1 (G protein-coupled estrogen receptor 1) [NCBI Gene 2852] {aka CEPR, CMKRL2, DRY12, FEG-1, GPCR-Br, GPER}, APOL3 (apolipoprotein L3) [NCBI Gene 80833] {aka APOLIII, CG121, CG12_1, apoL-III}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, APOC1 (apolipoprotein C1) [NCBI Gene 341] {aka APOC1B, Apo-CI, ApoC-I, apo-CIB, apoC-IB}, APOM (apolipoprotein M) [NCBI Gene 55937] {aka G3a, HSPC336, NG20, apo-M}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, APOA4 (apolipoprotein A4) [NCBI Gene 337] {aka ADTKD6}, APOL5 (apolipoprotein L5) [NCBI Gene 80831] {aka APOL-V, APOLV}, APOB (apolipoprotein B) [NCBI Gene 338] {aka FCHL2, FLDB, LDLCQ4, apoB-100, apoB-48}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, APOL1 (apolipoprotein L1) [NCBI Gene 8542] {aka APO-L, APOL, APOL-I, FSGS4}, APOLD1 (apolipoprotein L domain containing 1) [NCBI Gene 81575] {aka BDVAS, VERGE}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, AOPEP (aminopeptidase O (putative)) [NCBI Gene 84909] {aka AP-O, APO, C90RF3, C9orf3, DYT31, ONPEP}, APOA5 (apolipoprotein A5) [NCBI Gene 116519] {aka APOAV, RAP3}, APOA1 (apolipoprotein A1) [NCBI Gene 335] {aka AMYLD3, HPALP2, apo(a)}, APOO (apolipoprotein O) [NCBI Gene 79135] {aka FAM121B, MIC26, MICOS26, Mic23, My025}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633] {aka VSIG9, VSTM3, WUCAM}, CLU (clusterin) [NCBI Gene 1191] {aka AAG4, APO-J, APOJ, CLI, CLU1, CLU2}, APOC4 (apolipoprotein C4) [NCBI Gene 346] {aka APO-CIV, APOC-IV}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}
- **Diseases:** Obesity (MESH:D009765), gastric cancer (MESH:D013274), APOs (MESH:D052476), cholangiocarcinoma (MESH:D018281), metabolic disorder (MESH:D008659), OS (MESH:C567932), pancreatic ductal adenocarcinoma (MESH:D021441), HL (MESH:C538324), prostate cancer (MESH:D011471), small cell lung cancer (MESH:D055752), pancreatic cancer (MESH:D010190), lung cancer (MESH:D008175), Alzheimer's disease (MESH:D000544), Cancer (MESH:D009369), uterus benign myoma (MESH:D009214), uterine fibroids (MESH:D007889), breast cancer (MESH:D001943), ovarian cancer (MESH:D010051), HCC (MESH:D006528), bladder cancer (MESH:D001749), UALCAN (MESH:C566784), EC (MESH:D016889), colorectal cancer (MESH:D015179), OS (MESH:D011475), cardiovascular disease (MESH:D002318), gynecological malignancy (MESH:D005833)
- **Chemicals:** TBS (MESH:D013725), SDS (MESH:D012967), artesunate (MESH:D000077332), glycine (MESH:D005998), 17beta-estradiol (MESH:D004958), streptomycin (MESH:D013307), carbon (MESH:D002244), CO2 (MESH:D002245), lipid (MESH:D008055), polyvinylidene difluoride (MESH:C024865), DMSO (MESH:D004121), Dulbecco's modified Eagle's medium (-), phenol red (MESH:D010637), penicillin (MESH:D010406)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** Ishikawa — Homo sapiens (Human), Type I endometrial adenocarcinoma, Cancer cell line (CVCL_2529), EC — Homo sapiens (Human), Type II endometrial adenocarcinoma, Cancer cell line (CVCL_1274)

## Full text

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## Figures

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## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12950738/full.md

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Source: https://tomesphere.com/paper/PMC12950738