# Combined assessment of ERO1A expression and CD163+ tumor-associated macrophage infiltration is superior to traditional assessment methods in predicting clear cell renal cell carcinoma prognosis

**Authors:** Tianyu Hong, Changjie Ren, Hao Xiang, Huaye Wu, Yongwei Yu, Mierxiati Abudurexiti, Zhong Wang, Chao Wang

PMC · DOI: 10.3389/fonc.2026.1732415 · Frontiers in Oncology · 2026-02-23

## TL;DR

Combining ERO1A expression and CD163+ macrophage levels improves survival prediction in kidney cancer patients compared to traditional methods.

## Contribution

The study introduces a novel combined biomarker approach using ERO1A and CD163+ TAMs for more accurate ccRCC prognosis.

## Key findings

- ERO1A expression is elevated in ccRCC and correlates with disease progression and CD163+ TAM infiltration.
- High ERO1A and CD163+ TAM levels are linked to worse survival and higher clinical scores in ccRCC patients.
- Combining ERO1A, CD163+ TAMs, and TNM/SSIGN scores provides superior survival prediction accuracy.

## Abstract

The interplay between cancer cells and tumor-infiltrating immune cells (TIICs) facilitates the development of clear cell renal cell carcinoma (ccRCC). However, it remains unclear whether the combined assessment of tumor biomarkers and TIIC density increases the accuracy of ccRCC prognosis prediction.

ERO1A expression was detected in ccRCC tissue samples and cell lines. ccRCC patients from two hospitals were recruited to investigate the value of ERO1A and other TIIC biomarkers in determining ccRCC prognosis via immunohistochemistry (IHC) and statistical analyses.

Compared with that in the corresponding controls, ERO1A expression in ccRCC cell lines and tissues was increased and closely correlated with ccRCC progression. ERO1A expression was positively correlated with the density of infiltrating CD163+ tumor-associated macrophages (TAMs) in ccRCC. Among all groups of patients, ccRCC patients with high expression of both ERO1A and CD163 presented the highest TNM stage or Mayo Clinic stage, size, grade, and necrosis (SSIGN) score, as well as the shortest survival period. Moreover, the independent risk factors for the survival of ccRCC patients included ERO1A expression, CD163+ TAM density, TNM stage, and the SSIGN score. Time-dependent C-index analysis revealed that the combination of ERO1A expression and CD163+ TAM density was superior to either factor alone in predicting ccRCC patient survival. Furthermore, the combination of ERO1A expression and CD163+ TAM density with TNM stage or the SSIGN score had the greatest ability to predict the survival of ccRCC patients.

Combining ERO1A expression, CD163+ TAM density, and TNM stage or SSIGN score increases the accuracy of postoperative survival prediction for ccRCC patients.

Compared with currently available biomarkers, the combination of ERO1A expression and the density of infiltrating CD163+ TAMs with TNM stage or the SSIGN score exhibits greater accuracy in evaluating ccRCC patient survival.

## Linked entities

- **Genes:** ERO1A (endoplasmic reticulum oxidoreductase 1 alpha) [NCBI Gene 30001]
- **Proteins:** CD163 (CD163 molecule)
- **Diseases:** clear cell renal cell carcinoma (MONDO:0005005), ccRCC (MONDO:0007763)

## Full-text entities

- **Genes:** BRCA2 (BRCA2 DNA repair associated) [NCBI Gene 675] {aka BRCC2, BROVCA2, FACD, FAD, FAD1, FANCD}, LINC00926 (long intergenic non-protein coding RNA 926) [NCBI Gene 283663], CMPK1 (cytidine/uridine monophosphate kinase 1) [NCBI Gene 51727] {aka CK, CMK, CMPK, UMK, UMP-CMPK, UMPK}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, Cd163 (CD163 antigen) [NCBI Gene 93671] {aka CD163v2, CD163v3}, AURKB (aurora kinase B) [NCBI Gene 9212] {aka AIK2, AIM-1, AIM1, ARK-2, ARK2, AurB}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, ANGPTL4 (angiopoietin like 4) [NCBI Gene 51129] {aka ARP4, FIAF, HARP, HFARP, NL2, PGAR}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, SOX17 (SRY-box transcription factor 17) [NCBI Gene 64321] {aka PPH7, VUR3}, PSMD10 (proteasome 26S subunit, non-ATPase 10) [NCBI Gene 5716] {aka dJ889N15.2, p28, p28(GANK)}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, ERO1A (endoplasmic reticulum oxidoreductase 1 alpha) [NCBI Gene 30001] {aka ERO1-L, ERO1-L-alpha, ERO1-alpha, ERO1L, ERO1LA, Ero1alpha}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, Ero1a (endoplasmic reticulum oxidoreductase 1 alpha) [NCBI Gene 50527] {aka ERO1-L, Ero1l}, Tff2 (trefoil factor 2 (spasmolytic protein 1)) [NCBI Gene 21785] {aka SP, mSP}, CD163 (CD163 molecule) [NCBI Gene 9332] {aka M130, MM130, SCARI1}, P4HB (prolyl 4-hydroxylase subunit beta) [NCBI Gene 5034] {aka CLCRP1, DSI, ERBA2L, GIT, P4Hbeta, PDI}
- **Diseases:** Clear cell renal cell carcinoma (MESH:D002292), TIICs (MESH:D018270), necrosis (MESH:D009336), colorectal cancer (MESH:D015179), metastasis (MESH:D009362), cholangiocarcinoma (MESH:D018281), TAM (MESH:D020914), hypoxic (MESH:D002534), pancreatic ductal adenocarcinoma (MESH:D021441), inflammatory (MESH:D007249), lung cancer (MESH:D008175), Tumor (MESH:D009369)
- **Chemicals:** paraformaldehyde (MESH:C003043), citrate (MESH:D019343), CO2 (MESH:D002245), eosin (MESH:D004801), penicillin (MESH:D010406), hematoxylin (MESH:D006416), disulfide (MESH:D004220), DAB (-), crystal violet (MESH:D005840), H&amp;E (MESH:D006371), pazopanib (MESH:C516667), Lipofectamine (MESH:C086724), TRIzol (MESH:C411644), CCK 8 (MESH:D012844), Sunitinib (MESH:D000077210), biotin (MESH:D001710), paraffin (MESH:D010232), methanol (MESH:D000432), streptomycin (MESH:D013307), EDTA (MESH:D004492)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mycoplasma (genus) [taxon 2093], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** A498 — Homo sapiens (Human), Renal cell carcinoma, Cancer cell line (CVCL_1056), 769-P — Homo sapiens (Human), Renal cell carcinoma, Cancer cell line (CVCL_1050), ACHN — Homo sapiens (Human), Papillary renal cell carcinoma, Cancer cell line (CVCL_1067), 786-O — Homo sapiens (Human), Renal cell carcinoma, Cancer cell line (CVCL_1051), U937 — Homo sapiens (Human), Adult acute monocytic leukemia, Cancer cell line (CVCL_0007)

## Full text

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## Figures

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## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12968006/full.md

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Source: https://tomesphere.com/paper/PMC12968006