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. 2024 Jul 7;24(1):811.
doi: 10.1186/s12885-024-12586-y.

KK-LC-1, a biomarker for prognosis of immunotherapy for primary liver cancer

Sihui Zhu  1   2   3 , Yuncheng Jin  1   3 , Mingzhen Zhou  1   3 , Lin Li  1   3   4 , Xueru Song  1   3 , Xinyu Su  1   3 , Baorui Liu  5   6 , Jie Shen  7   8
Affiliations

KK-LC-1, a biomarker for prognosis of immunotherapy for primary liver cancer

Sihui Zhu et al. BMC Cancer. .

Abstract

Purpose: There is mounting evidence that patients with liver cancer can benefit from Immune checkpoint inhibitors. However, due to the high cost and low efficacy, we aimed to explore new biomarkers for predicting the efficacy of immunotherapy.

Methods: Specimens and medical records of liver cancer patients treated at Drum Tower Hospital of Nanjing University were collected, and the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in tissues as well as the corresponding antibodies in serum were examined to find biomarkers related to the prognosis of immunotherapy and to explore its mechanism in the development of liver cancer.

Results: KK-LC-1 expression was found to be 34.4% in histopathological specimens from 131 patients and was significantly correlated with Foxp3 expression (P = 0.0356). The expression of Foxp3 in the tissues of 24 patients who received immunotherapy was significantly correlated with overall survival (OS) (P = 0.0247), and there was also a tendency for prolonged OS in patients with high expression of KK-LC-1. In addition, the expression of KK-LC-1 antibody in the serum of patients who received immunotherapy with a first efficacy evaluation of stable disease (SD) was significantly higher than those with partial response (PR) (P = 0.0413).

Conclusions: Expression of KK-LC-1 in both tissues and serum has been shown to correlate with the prognosis of patients treated with immunotherapy, and KK-LC-1 is a potential therapeutic target for oncological immunotherapy.

Keywords: Biomarkers; Hepatocellular carcinoma; Immunotherapy.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
a: High expression of KK-LC-1. b: Low expression of KK-LC-1. c: Searching the TCGA database and plotting survival curves based on KK-LC-1 expression, patients with high KK-LC-1 expression had lower OS than those with low KK-LC-1 expression (P = 0.0040). d: Relationship between KK-LC-1 expression level and OS in patients
Fig. 2
Fig. 2
a: High expression of Foxp3. b: Low expression of Foxp3. c: Relationship between Foxp3 expression levels and the OS in patients. d: KK-LC-1 showed a significant negative correlation with Foxp3 expression. e: Relationship between KK-LC-1 expression levels and the OS in patients
Fig. 3
Fig. 3
a: The relationship between the expression of KK-LC-1 antibody with the efficacy of immunotherapy before this treatment. b: The relationship between the expression of KK-LC-1 antibody with the efficacy of immunotherapy after this treatment. c: (1) Changes in KK-LC-1 antibody expression before and after immunotherapy in patients with PR. (2) Changes in KK-LC-1 antibody expression before and after immunotherapy in patients with SD. d: Relationship between tumor regression rate and patient survival. e. The rate of tumor regression in patients tends to decrease in absolute value over time
Fig. 4
Fig. 4
a: Antigenic peptides stimulate PBMCs. b: Validation of the cytotoxicity of reactive T cells against tumor cells with differential expression of KK-LC-1 in vitro
Fig. 5
Fig. 5
a: Differential genes of sh-hep-1-KK-LC-1 and sk-hep-1-con cells. b: GO pathway enriched by differential genes of sh-hep-1-KK-LC-1 and sk-hep-1-con cells. c: Differential genes enriched in MAPK signaling pathway. d: KEGG pathway enriched by differential genes of sh-hep-1-KK-LC-1 and sk-hep-1-con cells
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