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Pan‑cancer analysis of the oncogenic role of SRY‑related high‑mobility group box protein B5 in human tumors

  • Authors:
    • Yajun Tong
    • Huini Da
    • Kewei Tang
    • Qiang Zhou
    • Songlian Liu
    • Leilan Yin
    • Ling Long
    • Site Bai
    • Ludi Ou
    • Qinghua Yin
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Yueyang Central Hospital, Yueyang, Hunan 414000, P.R. China, Department of Urology, Yueyang Central Hospital, Yueyang, Hunan 414000, P.R. China, Department of Oncology, Yueyang Central Hospital, Yueyang, Hunan 414000, P.R. China
    Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 32
    |
    Published online on: November 28, 2025
       https://doi.org/10.3892/etm.2025.13027
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Abstract

SRY‑related high‑mobility group protein B5 (SOX5) functions as an oncogene in diverse human malignancies, contributing to tumor progression, metastasis and therapy resistance across various cancer types. In light of this, a pan‑cancer analysis was performed in the present study to investigate the oncogenic function of SOX5 in various human malignancies. SOX5 mRNA expression levels were compared between normal and malignant tissues using The Cancer Genome Atlas database and diagnostic effectiveness was evaluated using receiver operating characteristic curve analysis. Kaplan‑Meier survival analysis was performed to investigate the association between SOX5 expression and overall survival, disease‑specific survival, disease‑free interval and progression‑free interval. The influence of SOX5 on immune infiltration and immunological scores in the tumor microenvironment was assessed utilizing Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data, Cell‑Type Identification by Estimating Relative Subsets of RNA Transcripts and single‑sample Gene Set Enrichment Analysis methodologies, in conjunction with its relationship to drug sensitivity and genetic modifications. SOX5 exhibited tissue‑specific dysregulation, being markedly downregulated in carcinomas such as lung adenocarcinoma (LUAD), lung squamous cell carcinoma and breast cancer, while increased in testicular germ cell tumor and non‑small cell lung cancer (NSCLC) cell lines. It demonstrated notable diagnostic potential, with good performance in LUAD (area under the curve=0.916). The prognostic relevance of SOX5 was contingent upon context as lower expression conferred protection in specific malignancies; however, it was associated with worse outcomes in others, such as low‑grade glioma and pancreatic adenocarcinoma. Increased SOX5 expression was associated with an immunosuppressive milieu marked by a rise in regulatory T cells, a decline in cytotoxic T cells and the activation of immunological checkpoints including programmed death‑ligand 1 and cytotoxic T lymphocyte associated protein 4. Moreover, SOX5 was associated with genomic instability, susceptibility to medicines such as azacitidine and distinct mutation patterns. SOX5 suppression in NSCLC cells in vitro impeded proliferation, migration and invasion. These findings collectively emphasize the key function of SOX5 in tumor biology and highlight its potential as a biomarker for cancer diagnosis, prognosis and therapeutic targeting.
View Figures

Figure 1

SOX5 expression in human cancers. (A)
Boxplots illustrating the mRNA expression levels of SOX5 in normal
and cancer tissues using data from TCGA database. Tumor tissues are
represented by blue dots and boxes, while normal tissues are
represented by orange dots and boxes. (B) Boxplots showing the mRNA
expression levels of SOX5 in normal and cancer tissues using data
from TCGA database. Tumor tissues are represented by red boxes and
normal tissues are represented by blue boxes.
*P<0.05; **P<0.01;
***P<0.001; ****P<0.0001. ns, not
significant; TCGA, The Cancer Genome Atlas; GTEx, Genotype-Tissue
Expression program; SOX5, SRY-related high-mobility group box
protein B5.

Figure 2

Diagnostic and prognostic value of
SOX5 in pan-cancer. (A) ROC curves for diagnosing 15 cancers based
on SOX5 expression. (B) Boxplots showing the association between
SOX5 expression levels and seven clinical characteristics in 30
cancer types. (C) Circular histogram of OS, DSS, DFI and PFI of
SOX5 in 44 types of cancer using Kaplan-Meier analysis.
*P<0.05; **P<0.01;
***P<0.001. ns, not significant; ROC, receiver
operator characteristic; SOX5, SRY-related high-mobility group box
protein B5; OS, overall survival; DSS, disease-specific survival;
DFI, disease-free interval; PFI, progression-free interval; BLCA,
bladder urothelial carcinoma; BRCA, breast invasive carcinoma;
COAD, colon adenocarcinoma; ESCA, esophageal carcinoma; KICH,
kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP,
kidney renal papillary cell carcinoma; LIHC, liver hepatocellular
carcinoma; HNSC, head and neck squamous cell carcinoma; LUAD, lung
adenocarcinoma; LUSC, lung squamous cell carcinoma; PRAD, prostate
adenocarcinoma; STAD, stomach adenocarcinoma; THCA, thyroid
carcinoma; UCEC, uterine corpus endometrial carcinoma.

Figure 3

Influence of SOX5 expression on
antitumor immunity and immunotherapy response. (A) Correlation
between SOX5 and ESTIMATE scores (ESTIMATE Score, Immune Score and
Stromal Score). (B) Representative boxplots display the correlation
analysis of the cancer-immunity cycle in pan-cancer. The red boxes
represent the patients with high levels of SOX5, while blue boxes
represent the patients with low levels of SOX5. (C) The
relationship between SOX5 expression and tumor-infiltrating immune
cells. (D) Pan-cancer association between SOX5 expression and
Immune Checkpoint genes.(E) Relationship between SOX5 mRNA
expression and TMB. (F) Relationship between SOX5 mRNA expression
and MSI. *P<0.05; **P<0.01;
***P<0.001; ****P<0.0001. ns, not
significant; SOX5, SRY-related high-mobility group box protein B5;
TMB, tumor mutational burden; MSI, microsatellite instability;
ESTIMATE, Estimation of Stromal and Immune Cells in Malignant Tumor
Tissues Using Expression Data; NK, natural killer; TME, tumor
microenvironment.

Figure 4

Drug sensitivity analysis. The top 12
SRY-related high-mobility group box protein B5 positively
correlated drugs from the Genomics of Drug Sensitivity in Cancer 2
database.

Figure 5

Mutation character of SOX5 in
pan-cancer. (A) Alteration frequency of SOX5 in pan-cancer. (B) The
subtypes and distributions of SOX5 somatic mutations. (C) Waterfall
plots of differential somatic mutations in lung adenocarcinoma,
including the SOX5high group and the SOX5low
groups. (D) Mutation of SOX5 relation to the mutation of specific
signal pathway genes (P<0.05). SOX5, SRY-related high-mobility
group box protein B5; OR, odds ratio; CAN, copy number alteration;
VUS, variant of uncertain significance; HMG_box, high-mobility
group box.

Figure 6

Enrichment analysis of SOX5
co-expression genes in LUAD. (A) The SOX5 co-expression genes in
LUAD. (B-C) The top 50 genes were positively and negatively
correlated with SOX5. (D) GO and (E) Kyoto Encyclopedia of Genes
and Genomes analysis of co-expression genes of SOX5 in the LUAD
cohort. SOX5, SRY-related high-mobility group box protein B5; GO,
Gene Ontology; LUAD, lung adenocarcinoma; BP, biological process;
CC, cellular component; MF, molecular function.

Figure 7

Effect of the SOX5 gene on the
biological behavior of non-small cell lung cancer. (A) The
expression levels of SOX5 in non-small cell lung cancer cell lines
(H1299 and A549) and normal human bronchial epithelial cells
(BEAS-2B) were quantified using qPCR. Statistical significance was
assessed using a one-way ANOVA followed by Tukey's post hoc test.
(B) Validation of SOX5 knockdown in the A549 cell line. The
relative mRNA expression level of SOX5 was determined by
quantitative PCR in control and SOX5 knockdown groups. Gene
expression was calculated using the 2-ΔΔCq method and
normalized to GAPDH. Differences among the groups over time were
analyzed using a one-way ANOVA followed by Tukey's post hoc test.
(C) Cell Counting Kit-8 assay was carried out to assess cell
viability in transfected A549 cells. Differences among the groups
over time were analyzed using a one-way ANOVA followed by Tukey's
post hoc test. (D-E) A wound healing assay was used to assess the
migratory abilities of transfected A549 cells. Statistical analysis
was performed using a one-way ANOVA followed by Tukey's post hoc
test. (F-G) Cell invasion was examined using a Transwell assay in
transfected A549 cells. Statistical analysis was performed using a
one-way ANOVA followed by Tukey's post hoc test. Data are presented
as mean ± SD (n=3). *P<0.05; **P<0.01;
***P<0.001. SOX5, SRY-related high-mobility group box
protein B5; qPCR, quantitative PCR; si, small interfering RNA; NC,
negative control; pcDNA, plasmid cloning DNA.
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Copy and paste a formatted citation
Spandidos Publications style
Tong Y, Da H, Tang K, Zhou Q, Liu S, Yin L, Long L, Bai S, Ou L, Yin Q, Yin Q, et al: Pan‑cancer analysis of the oncogenic role of SRY‑related high‑mobility group box protein B5 in human tumors. Exp Ther Med 31: 32, 2026.
APA
Tong, Y., Da, H., Tang, K., Zhou, Q., Liu, S., Yin, L. ... Yin, Q. (2026). Pan‑cancer analysis of the oncogenic role of SRY‑related high‑mobility group box protein B5 in human tumors. Experimental and Therapeutic Medicine, 31, 32. https://doi.org/10.3892/etm.2025.13027
MLA
Tong, Y., Da, H., Tang, K., Zhou, Q., Liu, S., Yin, L., Long, L., Bai, S., Ou, L., Yin, Q."Pan‑cancer analysis of the oncogenic role of SRY‑related high‑mobility group box protein B5 in human tumors". Experimental and Therapeutic Medicine 31.2 (2026): 32.
Chicago
Tong, Y., Da, H., Tang, K., Zhou, Q., Liu, S., Yin, L., Long, L., Bai, S., Ou, L., Yin, Q."Pan‑cancer analysis of the oncogenic role of SRY‑related high‑mobility group box protein B5 in human tumors". Experimental and Therapeutic Medicine 31, no. 2 (2026): 32. https://doi.org/10.3892/etm.2025.13027
Copy and paste a formatted citation
x
Spandidos Publications style
Tong Y, Da H, Tang K, Zhou Q, Liu S, Yin L, Long L, Bai S, Ou L, Yin Q, Yin Q, et al: Pan‑cancer analysis of the oncogenic role of SRY‑related high‑mobility group box protein B5 in human tumors. Exp Ther Med 31: 32, 2026.
APA
Tong, Y., Da, H., Tang, K., Zhou, Q., Liu, S., Yin, L. ... Yin, Q. (2026). Pan‑cancer analysis of the oncogenic role of SRY‑related high‑mobility group box protein B5 in human tumors. Experimental and Therapeutic Medicine, 31, 32. https://doi.org/10.3892/etm.2025.13027
MLA
Tong, Y., Da, H., Tang, K., Zhou, Q., Liu, S., Yin, L., Long, L., Bai, S., Ou, L., Yin, Q."Pan‑cancer analysis of the oncogenic role of SRY‑related high‑mobility group box protein B5 in human tumors". Experimental and Therapeutic Medicine 31.2 (2026): 32.
Chicago
Tong, Y., Da, H., Tang, K., Zhou, Q., Liu, S., Yin, L., Long, L., Bai, S., Ou, L., Yin, Q."Pan‑cancer analysis of the oncogenic role of SRY‑related high‑mobility group box protein B5 in human tumors". Experimental and Therapeutic Medicine 31, no. 2 (2026): 32. https://doi.org/10.3892/etm.2025.13027
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