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Upregulated KLF5 Is a Promising Biomarker for the Diagnosis and Prognosis of Hepatocelluar Carcinoma

  † Co-first authors.

Submitted:

27 August 2026

Posted:

27 August 2026

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Abstract
Background/Objective Krüppel-like factor 5 (KLF5) as a member of the zinc finger protein family has been reported in hepatocellular carcinoma (HCC). However, the KLF5 as a novel biomarker for patients with chronic liver diseases (CLD) remains to be identified. This study investigated the clinical values of KLF5 in CLD malignant transformation. Methods KLF5 transcripts from the TCGA database were analyzed with functions and related signaling pathways. Under the ethics committee consent, microarrays were constructed from HCC and noncancerous tissues. KLF5 distribution and expression were analyzed by multiplex immunofluorescence or Western blotting. Bloods were collected from a cohort of cases with CLD. Serum KLF5 levels were quantitatively detected by an enzyme-linked immune-sorbent assay. Results KLF5 at mRNA levels were signifi-cantly upregulating expressed (P<0.001) in HCC tissues more than these in normal livers from the TCGA database. Strong KLF5 expressions were verified in human HCC cell lines or tissues. Clini-copathological features of high KLF5 levels were remarked related (P<0.001) to tumor size, AFP level, HBV infection, tumor/node/metastasis stage and overall survival rate. Furthermore, the in-cidence of KLF5 in the HCC group were significantly higher (P<0.001) more than those in cases with liver cirrhosis or chronic hepatitis. Also, KLF5 was an independent prognostic factor for HCC. Interestingly, the co-expressions of KLF5 with Wnt3a promoted CLD malignant transfor-mation. Conclusion Upregulated KLF5 was associated with CLD malignancy and could be as a promising diagnostic or prognostic biomarker for HCC.
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