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Research Paper|Volume 15, Issue 20|pp 11588—11610

Immunobiological signatures and the emerging role of SPP1 in predicting tumor heterogeneity, malignancy, and clinical outcomes in stomach adenocarcinoma

Yanan Wu1, Lingyu Ren1, Yichun Tang2, Zhu Zhu2, Shifan Liu3, Yan Jiang4, Siming Zhang2, Xiaocan Zhuang1, Yuanbiao Chen5
  • 1Department of Gastroenterology, Rudong People’s Hospital, Rudong Hospital Affiliated to Nantong University, Nantong, China
  • 2Cancer Research Center Nantong, Nantong Tumor Hospital and Affiliated Tumor Hospital of Nantong University, Nantong, China
  • 3Department of Medical Imaging, Medical School of Nantong University, Nantong, China
  • 4Department of Engineering Training Center, Nantong University, Nantong, China
  • 5Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
* Equal contribution
Received: June 20, 2023Accepted: October 2, 2023Published: October 26, 2023
https://doi.org/10.18632/aging.205148

Copyright: © 2023 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Immunotherapy, as a form of immunobiological therapy, represents a promising approach for enhancing patients’ immune responses. This work aims to present innovative ideas and insights for prognostic assessment and clinical treatment of stomach adenocarcinoma (STAD) by leveraging immunobiological signatures.

Methods: We employed weighted gene co-expression network analysis (WGCNA) and unsupervised clustering analysis to identify hub genes. These hub genes were utilized to construct a prognostic risk model, and their impact on the tumor microenvironment (TME) and DNA variations was assessed using large-scale STAD patient cohorts. Additionally, we conducted transfection experiments with plasmids to investigate the influence of SPP1 on the malignancy of HGC27 and NCI-N87 cells.

Results: Unsupervised clustering of 12 immune-related genes (IRGs) revealed three distinct alteration patterns with unique molecular phenotypes, clinicopathological characteristics, prognosis, and TME features. Using LASSO and multivariate Cox regression analyses, we identified three hub genes (MMP12, SPP1, PLAU) from the IRGs to establish a risk signature. This IRG-related risk model significantly stratified the prognosis risk among STAD patients in the training (n = 522), testing (n = 521), and validation (n = 300) cohorts. Notably, there were discernible differences in therapy responses and TME characteristics, such as tumor purity and lymphocyte infiltration, between the risk model groups. Subsequently, a nomogram that incorporates the IRG signature and clinicopathological factors demonstrated superior sensitivity and specificity in predicting outcomes for STAD patients. Furthermore, down-regulation of SPP1, as observed after siRNA transfection, significantly inhibited the proliferation and migration abilities of HGC27 and NCI-N87 cells.

Conclusions: In summary, this study highlights the critical role of immune-related signatures in STAD and offers novel insights into prognosis indicators and immunotherapeutic targets for this condition. SPP1 emerges as an independent prognostic factor for STAD and appears to regulate STAD progression by influencing the immune microenvironment.