Method and application of INPP5J in hepatocellular carcinoma diagnosis, treatment and recurrence prediction

Abstract

The invention discloses a method and application of INPP5J in diagnosis, treatment and recurrence prediction of hepatocellular carcinoma, and belongs to the technical field of medical diagnosis, treatment and recurrence prediction, and the method comprises the following steps: step 1, integrating data of metabolic syndrome related liver cancer in a TCGA database based on a KEGG metabolism related gene set, taking an intersection of results of difference analysis with postoperative tumor and surrounding tissue transcriptome sequencing data of the operated metabolic syndrome-related liver cancer patient, and screening 20 metabolism-related genes as risk factors of postoperative high-risk recurrence of the liver cancer patient; by researching the expression and function of the INPP5J in the metabolic syndrome related hepatocellular carcinoma, the invention discloses an important role of the INPP5J in occurrence and development, treatment response and postoperative recurrence prediction of the liver cancer, and provides a new thought and method for precise diagnosis and treatment of the metabolic syndrome related hepatocellular carcinoma.

Description

Technical Field

[0001] The present invention relates to the technical field of medical diagnosis, treatment and prediction of recurrence, and specifically to a method and application of INPP5J in diagnosis, treatment and prediction of recurrence of hepatocellular carcinoma. Background Art

[0002] With the rapid economic development and changes in residents' lifestyles, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) caused by metabolic syndrome are becoming the fastest growing causes of primary liver cancer (hereinafter referred to as "liver cancer").

[0003] Due to the insidious onset of liver cancer and the lack of routine screening methods for metabolic syndrome-related malignant liver cancer, most patients are already in the middle and late stages when they seek medical treatment and cannot undergo radical resection. However, even if they can successfully undergo surgery in the early stages, the postoperative recurrence rate of these patients is significantly higher than that of other early liver cancer patients, with a recurrence rate of up to 48.3%. Therefore, in-depth elaboration of the postoperative recurrence mechanism of this type of liver cancer patients, screening and identification of targeted genes that inhibit tumor recurrence and progression, will help to further improve the long-term survival and quality of life of patients with metabolic syndrome-related liver cancer.

[0004] Inositol polyphosphate-5-phosphatase J (INPP5J) is a key enzyme that activates phosphatidylinositol-3,4,5-triphosphate 5-phosphatase activity and phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity, and is closely related to the regulation of intracellular signal transduction and the occurrence and development of tumors. INPP5J has been shown to be a prognostic marker for a variety of cancers, including lung adenocarcinoma, pancreatic cancer, and ovarian cancer. In metabolic syndrome-related liver cancer, the pathogenic mechanism of INPP5J is still unclear, and there has been no research on the prediction of postoperative recurrence. Therefore, methods and applications of INPP5J in the diagnosis, treatment, and prediction of recurrence of hepatocellular carcinoma are proposed.

[0005] The above information disclosed in this background technology is only used to increase the understanding of the background technology of the present invention and therefore, it may include information that does not constitute the prior art known to a person of ordinary skill in the art. Summary of the invention

[0006] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, one object of the present invention is to propose a method and application of INPP5J in the diagnosis, treatment and prediction of recurrence of hepatocellular carcinoma.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] The method of using INPP5J in diagnosis, treatment and prediction of recurrence of hepatocellular carcinoma comprises the following steps:

[0009] Step 1: Based on the KEGG metabolism-related gene set, the data of metabolic syndrome-related liver cancer in the TCGA database were integrated, and the results of differential analysis of postoperative tumor and surrounding tissue transcriptome sequencing data of patients with metabolic syndrome-related liver cancer who underwent surgery were intersected to screen 20 metabolism-related genes as risk factors for high-risk recurrence in patients with liver cancer after surgery;

[0010] Step 2: Cox univariate analysis was performed on the 20 genes screened to determine the genes associated with the risk of postoperative recurrence;

[0011] Step 3: Evaluate the correlation between INPP5J expression level and overall survival of patients by drawing KM survival curve analysis;

[0012] Step 4: qPCR was performed on tumor tissues and adjacent tissues of 12 patients with metabolic syndrome-related liver cancer who underwent resection surgery to verify the expression level of INPP5J in tumor tissues;

[0013] Step 5: Tumor tissues of 30 patients with metabolic syndrome-related liver cancer after HAIC treatment were selected for qPCR to evaluate the relationship between INPP5J expression level and treatment response;

[0014] Step 6: Analyze the postoperative pathological results and median recurrence-free survival (RFS) of 50 patients with metabolic syndrome-related liver cancer to determine the correlation between INPP5J expression level and postoperative recurrence risk.

[0015] Overall application of INPP5J in the diagnosis, treatment and prediction of recurrence of metabolic syndrome-related hepatocellular carcinoma.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] The present invention first discovered that INPP5J is upregulated in tumor tissues of patients with metabolic syndrome-related hepatocellular carcinoma, and proved that it is associated with the risk of postoperative recurrence, providing a new molecular marker for the early diagnosis of this type of liver cancer. It also first proposed that INPP5J can be used as a therapeutic target for metabolic syndrome-related hepatocellular carcinoma, providing a theoretical basis for the development of new therapeutic drugs.

[0018] The present invention can predict the risk of postoperative recurrence in patients with metabolic syndrome-related hepatocellular carcinoma by detecting the expression level of INPP5J, which helps clinicians to formulate more accurate treatment plans. The present invention found that the expression of INPP5J was significantly lower in patients with partial remission after HAIC treatment, suggesting that INPP5J may promote the progression of metabolic syndrome-related liver cancer as an oncogene and affect the treatment effect. It was found that patients with lower INPP5J expression in postoperative pathological samples had a longer recurrence-free survival period, further confirming the correlation between INPP5J and the risk of postoperative recurrence.

[0019] The above summary is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments and features described above, further aspects, embodiments and features of the present invention will be readily apparent by reference to the accompanying drawings and the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is a schematic diagram of the structure of the intersection of three gene sets in the present invention;

[0021] Figure 2 It is a schematic diagram of the structure of the Cox univariate analysis results of the screened genes in the present invention;

[0022] Figure 3 It is a schematic diagram of the relationship between the expression of INPP5J in the present invention and the overall survival of all liver cancer patients in the TCGA database;

[0023] Figure 4 It is a schematic diagram of the relationship between the expression of INPP5J in the present invention and the overall survival of patients with metabolic syndrome-related liver cancer in the TCGA database;

[0024] Figure 5 This is a schematic diagram of the expression level of INPP5J in tumor tissue and adjacent tissue of liver cancer patients with metabolic syndrome related to the present invention;

[0025] Figure 6 It is a schematic diagram of the expression level of INPP5J in tumor tissues of patients with metabolic syndrome-related liver cancer who respond (PR) and those who do not respond (NPR) after HAIC treatment in the present invention;

[0026] Figure 7 It is a structural schematic diagram of the relationship between the expression of INPP5J in postoperative pathological tissue and the recurrence-free survival period of patients with metabolic syndrome-related liver cancer in the present invention. DETAILED DESCRIPTION

[0027] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] The present invention provides a technical solution:

[0029] The method of using INPP5J in diagnosis, treatment and prediction of recurrence of hepatocellular carcinoma comprises the following steps:

[0030] Step 1: Based on the KEGG metabolism-related gene set, the data of metabolic syndrome-related liver cancer in the TCGA database were integrated, and then the results of differential analysis were taken with the postoperative tumor and surrounding tissue transcriptome sequencing data of patients with metabolic syndrome-related liver cancer who underwent surgery at the Sun Yat-sen University Cancer Center, and 20 metabolism-related genes were screened as risk factors for high-risk recurrence in patients with liver cancer after surgery.

[0031] Step 2: Cox univariate analysis was performed on the 20 genes screened, and the results showed that there were 5 genes with statistical differences.

[0032] Step 3: By drawing the KM survival curve analysis, only INPP5J showed a correlation between metabolic syndrome and liver cancer: the high or low expression of INPP5J was not related to the overall survival of patients in the total liver cancer patients in TCGA. After a separate analysis of the metabolic syndrome-related liver cancer patients in TCGA, it was found that the median overall survival of patients with high expression of INPP5J was lower.

[0033] Step 4: qPCR was performed on tumor tissues and adjacent tissues from 12 patients with metabolic syndrome-related liver cancer who underwent resection surgery. It was found that the expression of INPP5J was significantly upregulated in tumor tissues compared with adjacent tissues.

[0034] Step 5: Tumor tissues from 30 patients with metabolic syndrome-related liver cancer after HAIC treatment were selected for qPCR, and it was found that the expression of INPP5J was significantly lower in patients with partial remission, suggesting that INPP5J may act as an oncogene to promote the progression of metabolic syndrome-related liver cancer.

[0035] Step 6: By analyzing the postoperative pathological results and median RFS of 50 patients with metabolic syndrome-related liver cancer, the results showed that patients with lower INPP5J expression in postoperative pathological samples had a longer recurrence-free survival, suggesting that increased INPP5J is associated with a high risk of postoperative recurrence.

[0036] In summary, the present invention studies the expression and function of INPP5J in metabolic syndrome-related hepatocellular carcinoma, reveals its important role in the occurrence and development of liver cancer, treatment response and prediction of postoperative recurrence, and provides new ideas and methods for the precise diagnosis and treatment of metabolic syndrome-related hepatocellular carcinoma.

[0037] Parts not involved in the present invention are the same as the prior art or can be implemented by the prior art. Although the embodiments of the present invention have been shown and described, it is understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for using INPP5J in the diagnosis, treatment and prediction of recurrence of hepatocellular carcinoma, characterized in that: The following steps are involved: Step 1: Based on the KEGG metabolism-related gene set, the data of metabolic syndrome-related liver cancer in the TCGA database were integrated, and the results of differential analysis of postoperative tumor and surrounding tissue transcriptome sequencing data of patients with metabolic syndrome-related liver cancer who underwent surgery were intersected to screen 20 metabolism-related genes as risk factors for high-risk recurrence in patients with liver cancer after surgery; Step 2: Cox univariate analysis was performed on the 20 genes screened to determine the genes associated with the risk of postoperative recurrence; Step 3: Evaluate the correlation between INPP5J expression level and overall survival of patients by drawing KM survival curve analysis; Step 4: qPCR was performed on tumor tissues and adjacent tissues of 12 patients with metabolic syndrome-related liver cancer who underwent resection surgery to verify the expression level of INPP5J in tumor tissues; Step 5: Tumor tissues of 30 patients with metabolic syndrome-related liver cancer after HAIC treatment were selected for qPCR to evaluate the relationship between INPP5J expression level and treatment response; Step 6: Analyze the postoperative pathological results and median recurrence-free survival (RFS) of 50 patients with metabolic syndrome-related liver cancer to determine the correlation between INPP5J expression level and postoperative recurrence risk.

2. The overall application of INPP5J in the diagnosis, treatment and prediction of recurrence of metabolic syndrome-related hepatocellular carcinoma.

Images