A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

Pouria Samadi; Mina Shahnazari; Abolfazl Shekari; Fatemeh Maghool; Akram Jalali

doi:10.1186/s12935-023-03163-7

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

Cancer Cell Int. 2023 Dec 2;23(1):307. doi: 10.1186/s12935-023-03163-7.

Authors

Pouria Samadi^#^{1

2}, Mina Shahnazari^#^{1

2}, Abolfazl Shekari^#³, Fatemeh Maghool⁴, Akram Jalali⁵

Affiliations

¹ Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
² Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran.
³ Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
⁴ Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
⁵ Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. akram.jalali59@gmail.com.

^# Contributed equally.

Abstract

The HAND2-AS1 (HAND2 Antisense RNA 1) Long noncoding RNA (lncRNA) has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken. Here, based on the co-expression network analysis and construction of interacting lncRNA-mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation. Our study spans across 33 distinct cancer types, revealing the HAND2-AS1's aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1's engagement in tumor progression and its association with various immune pathways across diverse tumor classifications. Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8+ T cells, spanning a pan-cancer context. Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types. Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1. Our study unveils HAND2-AS1's potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The increased HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic strategy, and a focal point for immunotherapeutic interventions.

Keywords: HAND2-AS1; Immunotherapy; Pan-cancer; Prognostic biomarker; WGCNA.

Grants and funding

140206215079/Hamadan University of Medical Sciences