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Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in non‑functioning pituitary adenomas

  • Authors:
    • Jianyao Mao
    • Xi Chen
    • Wentao Zheng
    • Bosen Liu
    • Zhangyu Li
    • Yukui Li
    • Ping Zhong
    • Sifang Chen
    • Guowei Tan
    • Chen Wang
    • Jinli Sun
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361003, P.R. China, Department of Neurology, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian 361012, P.R. China, Department of Reproduction, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361003, P.R. China
    Copyright: © Mao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 168
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    Published online on: March 10, 2026
       https://doi.org/10.3892/ol.2026.15521
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Abstract

Pituitary adenomas constitute 10 to 25% of intracranial tumors, rendering them one of the most prevalent types of brain tumors. While the majority of pituitary adenomas are benign, ~35% exhibit invasive behavior. Compared with their non‑invasive counterparts, invasive pituitary adenomas are more challenging to manage, highlighting the need to elucidate their underlying pathogenesis. However, the molecular mechanisms driving the invasive behavior of these tumors remain incompletely understood. Thus, the present study employed an integrated proteomic and metabolomic approach to investigate the molecular features associated with tumor invasiveness in pituitary adenomas. The investigation was performed at the First Affiliated Hospital of Xiamen University (Xiamen, China). Fresh‑frozen tumor specimens were collected from 16 patients diagnosed with clinically non‑functioning pituitary adenomas. These samples were divided into two groups based on invasiveness: Invasive tumors (n=8; Knosp grade ≥2) and non‑invasive tumors (n=8; Knosp grade <2). Using data‑­independent acquisition mass spectrometry (MS) in conjunction with liquid chromatography‑MS/MS metabolomics analysis, differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs) were identified. Comparative analysis identified 614 DEPs, including 286 proteins that were upregulated and 328 that were downregulated in invasive tumors relative to non‑invasive tumors. Additionally, 74 DEMs were found, comprising 42 increased and 32 decreased metabolites. Enrichment analysis of pathways revealed notable involvement of the cyclic adenosine monophosphate (cAMP) signaling cascade, pathways related to pathogenic Escherichia coli (E. coli) infection and the synaptic vesicle cycle. Integration of the proteomic and metabolomic data underscored consistent changes within these biological pathways. The present investigation represents a comprehensive effort to combine proteomic and metabolomic approaches to characterize the invasive phenotype of pituitary adenomas. The identification of enriched pathways associated with cAMP signaling, E. coli infection and synaptic vesicle cycling provides new mechanistic understanding and offers potential biomarkers or therapeutic targets for differentiating tumor aggressiveness.
View Figures

Figure 1

Correlation heat map of differential
protein samples between the invasive group and non-invasive
group.

Figure 2

Statistics of differentially
expressed proteins between the invasive group and the non-invasive
group, and between the invasive group and the non-invasive group.
(A) A Volcano plot of P-value vs. log2(FC) in the
control group compared with the invasive group. Significantly
upregulated and downregulated proteins are highlighted (FC >1.2;
P≤0.05). Violin plot presenting differentially expressed proteins
(B) VAMP2, (C) TIAM1 and (D) TUBB1 between the invasive group and
the non-invasive groups. *P<0.05. FC, fold change.; VAMP2,
vesicle-associated membrane protein 2; TIAM1, T-cell lymphoma
invasion and metastasis-inducing protein 1; TUBB1, tubulin b1 class
VI.

Figure 3

Functional enrichment analysis of
DEPs between the invasive group and the non-invasive group. (A) The
20 GO terms that are most enriched, based on the DEPs, display
significantly modified expression patterns (FC >1.2;
FDR-adjusted P≤0.05). The X-axis displays the Rich factor, with the
color of the dot reflecting the significance of the change in
expression (adjusted P-value). The size of the dot represents the
number of proteins linked to each GO term. (B) KEGG pathway
analysis of differentially expressed genes. DEPs, differentially
expressed proteins; FDR, false discovery rate; FC, fold change; GO,
Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes.

Figure 4

Identification and visualization of
differential metabolites in invasive vs. non-invasive pituitary
adenomas. (A) Overview of differential metabolites identified in
the invasive group compared with the non-invasive group. Violin
plots displaying metabolites (B) L-glycine, (C) Gpetn(18:3/22:4)
and (D) 3-hydroxyoctanoic acid that showed differential expression
across the invasive and non-invasive groups. *P<0.05 and
***P<0.001. FC, fold change.

Figure 5

Functional enrichment analysis of
differential metabolites between the invasive group and the
non-invasive group.

Figure 6

Combined analysis of differential
proteins and metabolites between the invasive group and the
non-invasive group. KEGG, Kyoto Encyclopedia of Genes and
Genomes.
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Copy and paste a formatted citation
Spandidos Publications style
Mao J, Chen X, Zheng W, Liu B, Li Z, Li Y, Zhong P, Chen S, Tan G, Wang C, Wang C, et al: Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in non‑functioning pituitary adenomas. Oncol Lett 31: 168, 2026.
APA
Mao, J., Chen, X., Zheng, W., Liu, B., Li, Z., Li, Y. ... Sun, J. (2026). Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in non‑functioning pituitary adenomas. Oncology Letters, 31, 168. https://doi.org/10.3892/ol.2026.15521
MLA
Mao, J., Chen, X., Zheng, W., Liu, B., Li, Z., Li, Y., Zhong, P., Chen, S., Tan, G., Wang, C., Sun, J."Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in non‑functioning pituitary adenomas". Oncology Letters 31.5 (2026): 168.
Chicago
Mao, J., Chen, X., Zheng, W., Liu, B., Li, Z., Li, Y., Zhong, P., Chen, S., Tan, G., Wang, C., Sun, J."Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in non‑functioning pituitary adenomas". Oncology Letters 31, no. 5 (2026): 168. https://doi.org/10.3892/ol.2026.15521
Copy and paste a formatted citation
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Spandidos Publications style
Mao J, Chen X, Zheng W, Liu B, Li Z, Li Y, Zhong P, Chen S, Tan G, Wang C, Wang C, et al: Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in non‑functioning pituitary adenomas. Oncol Lett 31: 168, 2026.
APA
Mao, J., Chen, X., Zheng, W., Liu, B., Li, Z., Li, Y. ... Sun, J. (2026). Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in non‑functioning pituitary adenomas. Oncology Letters, 31, 168. https://doi.org/10.3892/ol.2026.15521
MLA
Mao, J., Chen, X., Zheng, W., Liu, B., Li, Z., Li, Y., Zhong, P., Chen, S., Tan, G., Wang, C., Sun, J."Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in non‑functioning pituitary adenomas". Oncology Letters 31.5 (2026): 168.
Chicago
Mao, J., Chen, X., Zheng, W., Liu, B., Li, Z., Li, Y., Zhong, P., Chen, S., Tan, G., Wang, C., Sun, J."Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in non‑functioning pituitary adenomas". Oncology Letters 31, no. 5 (2026): 168. https://doi.org/10.3892/ol.2026.15521
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