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Biomarker and application thereof in prognosis prediction of intrahepatic cholangiocellular carcinoma

A technology of biomarkers and inner bile duct, applied in the field of biomedicine, can solve the problem of little understanding of the role, and achieve a comprehensive effect of selection

Pending Publication Date: 2021-10-22
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the existing studies on methylation and intrahepatic cholangiocarcinoma mainly focus on the methylation level of single or multiple common tumor suppressor genes, such as CDH1, SOCS3, p15, hMLH1, APC, ARIDEAOPCML, etc. The remaining genes, as well as the role of methylation levels in specific gene regions on genes, in predicting long-term prognosis in intrahepatic cholangiocarcinoma are poorly understood

Method used

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  • Biomarker and application thereof in prognosis prediction of intrahepatic cholangiocellular carcinoma
  • Biomarker and application thereof in prognosis prediction of intrahepatic cholangiocellular carcinoma
  • Biomarker and application thereof in prognosis prediction of intrahepatic cholangiocellular carcinoma

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Embodiment 1

[0054] This example includes a multicenter and retrospective cohort of patients. Patients who underwent curative hepatectomy at West China Hospital of Sichuan University, Zhongshan Hospital of Fudan University, and Tianjin Medical University Cancer Hospital from May 2010 to July 2019 were studied. Considering clinicopathological and molecular heterogeneity, only patients with intrahepatic cholangiocarcinoma were included. All patients were first diagnosed with intrahepatic cholangiocarcinoma histologically, and patients with recurrent intrahepatic cholangiocarcinoma were not included. The study protocol was approved by the ethics committees of the three hepatobiliary centers and written informed consent was obtained from each patient before surgery.

[0055] A total of 334 patients selected from three hepatobiliary centers were divided into training and validation groups. Among them, 164 patients from the West China Hospital of Sichuan University (WCHSU cohort) were the trai...

Embodiment 2

[0060] Whole-genome DNA methylation sequencing was used for the patients in the training group to obtain the methylation level of the genome, and genes such as regions with identical CpG sites, regions with NA numbers not less than 16, and regions with a methylation level of 0 were removed. After regions, 1,028,088 gene regions were initially screened out of 1,606,362 gene regions.

[0061] Subsequently, further screening was performed from the initially screened gene regions. Such as figure 1 As shown, after further removing 12 gene regions with a methylation level of 0, 350 gene regions were screened using univariate Cox analysis, consistency index calculation, and coefficient of variation calculation. The 350 gene regions meet the following conditions: (1) p-value less than 0.001 in univariate Cox analysis; (2) C-index greater than 0.65; and (3) CV value greater than 0.2.

[0062] Finally, the LASSO Cox algorithm is used to compress high-dimensional data, and candidate ge...

Embodiment 3

[0069] In order to verify the stability of the GMS model, the GMS survey was first conducted in the training group (WCHSU cohort), and the C index of overall survival (OS) was 0.779 (95% CI: 0.738-0.820).

[0070] Such as image 3 As shown in (A), in the training group, the areas under the curve (AUC) of the overall survival at 1 year, 2 years, and 3 years were 0.859, 0.842, and 0.880, respectively. When applying the GMS model, the optimal cut-off value of the GMS model is determined to be -3.10 according to the surv_cutpoint function in the "survminer" package. By comparing the patient's GMS score with the cut-off value, the patients were divided into GMS low value group (GMS-low) and GMS high value group (GMS-high). Among them, there were 98 patients in the GMS low value group and 66 patients in the GMS high value group. Such as image 3 As shown in (B), the median overall survival period of the 98 patients in the low GMS group was 55.5±3.5 months, and the 1-year, 3-year,...

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Abstract

The invention relates to a biomarker and application thereof in prognosis prediction of intrahepatic cholangiocarcinoma, the biomarker is selected from a gene region of at least one gene of LIX1L, LINC01822, TUBA4A, AC023481.1, MFSD1, AC097173.1, FAM153B, STEAP2 / STEAP2-AS1, CDKN2B, FAM205BP, GAD2, LETMD1, RASSF3, AC073592.4, GOLGA6B, ORC6 and TMEM106A, and the gene region is an enhancer, a promoter, an exon, an intron, a 5'untranslated region or a 3 'untranslated region of the gene. Whole genome DNA methylation sequencing is adopted, the overall epigenetic change of the intrahepatic cholangiocarcinoma is described in the whole genome range, and the value of methylation levels of 17 gene areas in prognosis of the intrahepatic cholangiocarcinoma is systematically evaluated.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a biomarker and a model, product and system for predicting the prognosis of intrahepatic cholangiocarcinoma using the biomarker. Background technique [0002] Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant tumor arising from the liver itself, accounting for 4.8-12.0% of primary liver cancer, and its prognosis is poor. The incidence and mortality of intrahepatic cholangiocarcinoma have continued to rise over the past few decades. Complete surgical resection is the only option for long-term survival of patients with resectable intrahepatic cholangiocarcinoma, and the 5-year overall survival rate (overall survival, OS) of some patients is about 25.0-39.8%. [0003] The highly aggressive biological behavior of intrahepatic cholangiocarcinoma and the lack of specific symptoms and signs make most patients exhibit relatively advanced disease when they are first dia...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C12N15/11G16B20/30G16B40/00
CPCC12Q1/6886G16B20/30G16B40/00C12Q2600/154C12Q2600/118Y02A50/30
Inventor 曾勇高强孙德强袁克非陈璐陈星
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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