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CN-121992101-A - COTL1highApplication of NK cells as biomarkers in liver cancer prognosis

CN121992101ACN 121992101 ACN121992101 ACN 121992101ACN-121992101-A

Abstract

The invention discloses an application of COTL1 high NK cells as biomarkers in liver cancer prognosis. The invention is based on the intensive study of the tumor microenvironment, and finds that COTL1 high NK cells are highly enriched in liver cancer in response to Immune Checkpoint Blockade (ICB) treatment, and are associated with good prognosis. According to the method, the characteristic genes of the COTL1 high NK are analyzed, dynamic and polygenic expression information is obtained, a marker capable of predicting liver cancer prognosis is found, a liver cancer prognosis model is established according to the marker and is used for predicting liver cancer patient prognosis, and the prediction method can obtain dynamic and polygenic tumor microenvironment information and accurately predict liver cancer patient prognosis.

Inventors

  • CHEN YUN
  • YOU WENHUA
  • HU CHUPENG

Assignees

  • 南京医科大学

Dates

Publication Date
20260508
Application Date
20260204

Claims (10)

  1. Use of COTL1 high NK cells or COTL1 high NK characteristic gene expression in liver cancer prognosis.
  2. Application of COTL1 high NK cells or COTL1 high NK cell characteristic gene expression level in preparation of products for predicting liver cancer prognosis.
  3. 3. The application of a reagent and/or an instrument for detecting the expression quantity of COTL1 high NK cells or COTL1 high NK cell characteristic genes in preparing a product for predicting liver cancer prognosis.
  4. 4. The application of a system containing a reagent and/or an instrument for detecting the expression quantity of COTL1 high NK cells or COTL1 high NK cell characteristic genes in preparing a product for predicting liver cancer prognosis.
  5. 5. Use according to claim 3 or 4, wherein the test sample of the product is of human origin.
  6. 6. The use according to claim 3 or 4, wherein the test sample of the product is liver cancer tissue.
  7. 7. The use according to any one of claims 1 to 6, wherein the COTL1 high NK cell signature gene comprises any one or more of ：GZMK、COTL1、RGS1、CSF1、ITGA1、KLRC1、LAG3、HLA-DRA、NR4A2、CCL5、IGHG1、IGKC、LINC01871、 HLA-DRB1、CD74、PTMS、KIR2DL4、GBP5、ITGAE、IL32、ITM2A、STAT1、CLDND1、TNFAIP3、CD44、DUSP2、ITGB1、TRDC、GZMA、IL2RB、APOBEC3G、GBP4、CD69、CYTOR、CD52、CCND2、GBP2、CNN2、GBP1、RPS27、TBCD、JAK3、HLA-DPA1、RPS26、CLEC2B、CCL3、GPR171、RGS2、RPS15A、SLC2A3、PHYKPL、STK17B、VIM、CKLF、CD96、MCL1、PIM2、SH2D1A、HAVCR2、GAPDH、PSME2、RPL23A、TIGIT、TOX、GNAS、RPS17、HOPX、CD63、RPLP1、GPRIN3、DUSP1、 EVL、HSPA1B、RPL28、ERGIC1、MIF、LDHA、UBE2L6 or LAT 2.
  8. 8. A kit comprising a reagent for detecting the expression level of a characteristic gene of COTL1 high NK cells or COTL1 high NK cells.
  9. 9. The kit of claim 8, further comprising instructions for use in the kit.
  10. 10. Use of the kit according to any one of claims 8 or 9 for the preparation of a product for predicting prognosis of liver cancer.

Description

Application of COTL1 high NK cells as biomarker in liver cancer prognosis Technical Field The invention belongs to the technical field of biomedicine, and particularly relates to application of COTL1 high NK cells in liver cancer prognosis. Background Advanced liver cancer (HCC) is often associated with poor prognosis and negative treatment. Phase III clinical trials indicate that anti-angiogenic therapy in combination with PD-1/PD-L1 blockade can significantly extend the Overall Survival (OS) and progression-free survival of patients with advanced HCC. Despite the significant advances in surgical resection, interventional therapy and immunotherapy, current strategies for treating liver cancer remain limited in efficacy. Only 15-20% of HCC patients benefit from Immune Checkpoint Blockade (ICB) therapy, mainly due to heterogeneity and immunosuppression of Tumor Microenvironment (TME). Thus, there is an urgent need to intensively study the mechanism of immunotherapy resistance to enhance clinical benefit, and to find new biomarkers related to prognosis of liver cancer. The PD-1/PD-L1 immune checkpoint blockade therapy primarily salvages cd8+ T cells and enhances the cd8+ T cell anti-tumor immune response. Whereas cd8+ T cell mediated killing is primarily by recognition of antigens presented by the major histocompatibility complex (MHC-I). The primary reason for poor response to "cold" Tumor Microenvironment (TME) and Immune Checkpoint Blocking (ICB) therapies is due to a lack or down-regulation of tumor-specific MHC-I (tsMHC-I). Most patients initially respond to ICB therapy but experience secondary resistance due to antigen loss as a result of therapeutic stress. However, some patients with MHC-I overexpression still respond to ICB therapy, indicating potential innate immune cells, such as NK cells, to be involved in the anti-tumor immune response mediated by PD-1/PD-L1 therapy. The specific mechanism of tumor-specific MHC-I (tsMHC-I) expression and Immune Checkpoint Blockade (ICB) therapeutic response is currently being studied extensively, describing the correlation between immunotherapeutic response and the level of infiltration of COTL1high NK cells, indicating that COTL1high NK cells may be a prognostic and predictive factor, and therefore, predicting the prognosis of liver cancer based on the characteristics of COTL1 high NK cells is a promising strategy. COTL1 high NK cells present dual features of tissue resident NK cells and adaptive NK cells. In tumor immunity studies, tissue resident NK cells were found to be significantly associated with anti-tumor immunity and critical for cancer immune monitoring. We have found that a population of COTL1 high NK cells is highly enriched in tumor tissue of a well-predicted MHC-I-loss liver cancer patient and significantly enhances Immune Checkpoint Blockade (ICB) therapeutic response. This population of cells is associated with a positive anti-tumor immune response, and the collection of genetic components characteristic of this cell can predict survival prognosis for liver cancer. The tissue resident markers of the cells are (CD 49a, CD103 and ZNF 683) and the adaptive NK cell markers are (KLRC 2, CD52 and IL 32), and in summary, we developed a method for predicting prognosis of liver cancer patients by detecting COTL1 high NK in liver cancer tissues or detecting the characteristic gene expression quantity of COTL1 high NK. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide the application of COTL1 high NK cells in liver cancer prognosis. The technical scheme adopted for solving the technical problems is as follows: In a first aspect, the invention provides the use of COTL1 high NK cells or COTL1 high NK characteristic gene expression levels in liver cancer prognosis. Preferably, the invention also protects the application of the characteristic gene expression quantity of the COTL1 high NK cells or the COTL1 high NK cells in preparing products for predicting liver cancer prognosis. In a second aspect, the invention provides an application of a system for detecting the expression level of COTL1 high NK cells or COTL1 high NK cell characteristic genes in preparing a product for predicting liver cancer prognosis. In specific embodiments, the system for detecting COTL1 high NK cells or COTL1 high NK cell characteristic gene expression levels comprise reagents and/or instrumentation required to detect COTL1 high NK cells or COTL1 high NK cell characteristic gene expression levels. In particular embodiments, the test sample of the product is derived from a human. In a specific embodiment, the test sample of the product is liver cancer tissue. In more specific embodiments, the liver cancer tissue is fresh liver cancer tissue or paraffin-embedded liver cancer tissue. The characteristic gene set of the COTL1 high NK cell characteristic gene expression quantity comprises ：GZMK (Gene ID: 3003)、COTL1 (Gene ID: 23406)、RGS1 (Gene I