CN-116359499-B - Predictive biomarker TBC1D8 for colorectal cancer metastasis of human related to anoxic microenvironment and application thereof

Abstract

The invention discloses application of TBC1D8 as a TBC1 domain family member in preparing a predictive biomarker for prognosis and immunotherapeutic responsiveness of a human colorectal cancer patient. The correlation between TBC1D8 level and clinical characteristics and biological effects thereof is evaluated through the second generation sequencing result of a TCGA database and in-vitro and in-vivo experiments, the fact that the TBC1D8 level is increased and is related to poor prognosis of colorectal cancer patients is found, experimental researches also show that TBC1D8 is related to hypoxia microenvironment and can participate in regulating malignant phenotype of colorectal cancer cells and tumor cell stem property, in addition, TBC1D8 is closely related to infiltration of immunosuppressive macrophages, and experiments show that the reduction of TBC1D8 can obviously inhibit differentiation and infiltration of immunosuppressive macrophages. Thus, TBC1D8 can be used as a biomarker for prognosis of colorectal cancer patients, and can be a new target for treating colorectal cancer of people.

Inventors

• ZOU XI
• Li Jiepin
• LIU YUANJIE
• CHEN YUGEN

Assignees

• 江苏省中医院

Dates

Publication Date

20260505

Application Date

20220713

Claims (2)

1. Use of tbc1d8 protein in the preparation of a predictive biomarker for prognosis of a human colorectal cancer patient.
2. Use of tbc1d8 protein in the preparation of a kit for the prognosis of human colorectal cancer.

Description

Predictive biomarker TBC1D8 for colorectal cancer metastasis of human related to anoxic microenvironment and application thereof Technical Field The invention relates to a TBC1 domain family member, relates to a predictive biomarker TBC1D8 for prognosis of human colorectal cancer, and belongs to the technical field of biomedicine. Background Colorectal cancer (CRC) is one tumor of the gastrointestinal system, with the incidence rate being third among malignant tumors and the mortality rate being second among cancers. Its pathogenesis appears to involve a number of factors and steps, including genetics, diet and lifestyle. Statistics show that the tumor frequently recurs and metastasizes, particularly to the liver, lung, bone, ovary, peritoneum, with five-year survival rates of about 10% for such patients. Methods of treatment for CRC include chemotherapy, surgery, radiation therapy, and molecular targeted therapies. Molecular targeted treatment of CRC has become a hot topic. The number of molecular stratification treatment regimens is increasing, as are the use of biomarkers to guide prediction and treatment decisions. Thus, the identification of novel markers and targets for the treatment of CRC is essential for improving disease prognosis. The TBC (Tre-2/Bub 2/Cdc16, TBC) domain is a conserved amino acid sequence consisting of the domains of the tumor gene Tre-2 and the yeast cell cycle regulator genes Bub2 and Cdc 16. TBC-domain family members have strong conservation and high homology. TBC domains are often in tandem with other domains associated with cell membrane function, suggesting that the biological function of TBC domain proteins is intimately associated with the cell membrane and may mediate the development and progression of cancer or other diseases, some of which have in fact been found to be associated with the development of tumors. High levels of TBC1D7 have been observed in some lung cancers and are associated with poor prognosis in patients. RNAi interference with TBC1D7 in lung cancer cells inhibits cell growth, whereas overexpression of TBC1D7 promotes lung cancer cell proliferation and promotes mouse tumor formation. TBC1D16 also appears to be a driving gene for melanoma, whose overexpression can promote cell growth and gene expression, affect vesicle trafficking, and further affect the development of melanoma. Studies have shown that TBC1D8 is significantly upregulated in aggressive ovarian cancer cells, driving the development of ovarian cancer and metabolic reprogramming. However, little research has been done on its role in CRC. The present study attempts to fill this gap. Disclosure of Invention The invention aims to solve the technical problems of low biomarker accuracy for prognosis judgment of colorectal cancer patients and insufficient capability of metastasis prognosis of colorectal cancer patients in the existing clinical diagnosis. Through intensive research on TBC1D8, a large number of transcriptome data screening and clinical specimens and experimental verification prove that TBC1D8 can be used as a predictive biomarker for human colorectal cancer metastasis or used as a kit component for predicting or screening human colorectal cancer metastasis. The technical scheme adopted by the invention is as follows: A human colorectal cancer or a predictive biomarker for human colorectal cancer metastasis, characterized in that it belongs to the cytochrome C oxidase family GENE CARDS GENE Symbol: COX4I2. A predictive biomarker for human colorectal cancer immunotherapy responsiveness, characterized in that it belongs to TBC1 domain family member GENE CARDS GENE Symbol: TBC1D8. A kit for prognosis prediction or prognosis evaluation of immunotherapy for human colorectal cancer, comprising TBC1D8 protein. The amino acid sequence of the TBC1D8 protein is as follows: Met-Thr-Leu-Lys-Pro-Glu-Glu-Val-Leu-Leu-Lys-Asn-Ala-Leu-Lys-Leu-Trp-Val-Thr-Gln-Lys-Ser-Ser-Cys-Tyr-Phe-Ile-Leu-Gln-Arg-Arg-Arg-Gly-His-Gly-Glu-Gly-Gly-Gly-Arg-Leu-Thr-Gly-Arg-Leu-Val-Gly-Ala-Leu-Asp-Ala-Val-Leu-Asp-Ser-Asn-Ala-Arg-Val-Ala-Pro-Phe-Arg-Ile-Leu-Leu-Gln-Val-Pro-Gly-Ser-Gln-Val-Tyr-Ser-Pro-Ile-Ala-Cys-Gly-Ala-Thr-Leu-Glu-Glu-Ile-Asn-Gln-His-Trp-Asp-Trp-Leu-Glu-Gln-Asn-Leu-Leu-His-Thr-Leu-Ser-Val-Phe-Asp-Asn-Lys-Asp-Asp-Ile-Ala-Ser-Phe-Val-Lys-Gly-Lys-Val-Lys-Ala-Leu-Ile-Ala-Glu-Glu-Thr-Ser-Ser-Arg-Leu-Ala-Glu-Gln-Glu-Glu-Glu-Pro-Glu-Lys-Phe-Arg-Glu-Ala-Leu-Val-Lys-Phe-Glu-Ala-Arg-Phe-Asn-Phe-Pro-Glu-Ala-Glu-Lys-Leu-Val-Thr-Tyr-Tyr-Ser-Cys-Cys-Cys-Trp-Lys-Gly-Arg-Val-Pro-Arg-Gln-Gly-Trp-Leu-Tyr-Leu-Ser-Ile-Asn-His-Leu-Cys-Phe-Tyr-Ser-Phe-Phe-Leu-Gly-Lys-Glu-Leu-Lys-Leu-Val-Val-Pro-Trp-Val-Asp-Ile-Gln-Lys-Leu-Glu-Arg-Thr-Ser-Asn-Val-Phe-Leu-Thr-Asp-Thr-Ile-Arg-Ile-Thr-Thr-Gln-Asn-Lys-Glu-Arg-Asp-Phe-Ser-Met-Phe-Leu-Asn-Leu-Asp-Glu-Val-Phe-Lys-Val-Met-Glu-Gln-Leu-Ala-Asp-Val-Thr-Leu-Arg-Arg-Leu-Leu-Asp-Asn-Glu-Val-Phe-Asp-Leu-Asp-Pro-Asp-Leu-Gln-Glu-Pro-Ser-Gln-Ile-Thr-Lys-Arg-Asp-Leu-Glu-Ala-Arg-Ala-Gln-Asn-Glu-P