Upregulation of LINC00665 Correlates with Aggressive Hepatocellular Carcinoma and Poor Prognosis

Qiangqiang Zhong; Baokang Zhao; Yunhua Zhou; Xiangjie Liu

doi:10.2174/0113862073389839251128150111

Upregulation of LINC00665 Correlates with Aggressive Hepatocellular Carcinoma and Poor Prognosis

Comb Chem High Throughput Screen. 2026 Mar 11. doi: 10.2174/0113862073389839251128150111. Online ahead of print.

Authors

Qiangqiang Zhong¹, Baokang Zhao², Yunhua Zhou³, Xiangjie Liu⁴

Affiliations

¹ Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Wound Repair, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Geriatrics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

PMID: 41830138
DOI: 10.2174/0113862073389839251128150111

Abstract

Introduction: Recent research has revealed that LINC00665 is crucial for cancer cell proliferation and metastasis. Despite its presence, the role of LINC00665 in diagnosing and predicting outcomes in HCC remains poorly studied.

Methods: This study analyzed LINC00665 expression in TCGA and GTEx datasets and examined its association with clinicopathological characteristics. The association between LINC00665 and HCC prognosis was examined through survival and Cox regression analyses. To investigate the pathways associated with LINC00665 in HCC, we conducted GSEA. Additionally, the association between LINC00665 and immune cell infiltration was assessed through a comprehensive immune landscape analysis. Finally, multiple in vitro experiments validated the function of LINC00665 in accelerating HCC progression.

Results: Our study demonstrated a significant upregulation of LINC00665 in hepatocellular carcinoma (HCC). Elevated LINC00665 expression was strongly associated with adverse clinicopathological features, poor prognosis, and an immunosuppressive tumor microenvironment. Gene set enrichment analysis (GSEA) revealed that LINC00665 participates in multiple established oncogenic pathways. Furthermore, we observed noTable alterations in immune cell populations associated with its expression. Functional assays showed that silencing LINC00665 significantly inhibited tumor cell proliferation and invasive potential, highlighting its role as a potential therapeutic target in HCC.

Discussion: This study establishes LINC00665 as a critical oncogenic driver and prognostic biomarker in HCC, closely associated with tumor proliferation, metastasis, and an immunosuppressive microenvironment. While these findings underscore its clinical significance, further experimental and clinical validation is necessary to translate this insight into effective therapeutic strategies.

Conclusions: To sum up, LINC00665 has potential as an oncogenic biomarker in several cancers, underscoring the need for further study.

Keywords: LINC00665.; Liver cancer; biomarkers; pan-cancer; prognosis.