Tumor immune typing method based on lncRNA markers

An immunophenotyping and marker technology, applied in the field of biomedicine, can solve problems such as the inability to meet individualized immunotherapy

Active Publication Date: 2021-09-07
SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional tumor typing, grading, and staging can no longer meet the needs of individualized immunotherapy, especially the prediction of the curative effect and prognosis of the rapidly developing anti-tumor immunotherapy drugs.

Method used

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  • Tumor immune typing method based on lncRNA markers
  • Tumor immune typing method based on lncRNA markers
  • Tumor immune typing method based on lncRNA markers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1 Screening lncRNA

[0037] 1. Data source

[0038] 348 patients with bladder cancer treated with the PD-L1 inhibitor atotuzumab from the IMvigor 210 trial (NCT02951767 / NCT02108652, http: / / research-pub.gene.com / IMvigor210CoreBiologies) and 70 patients with melanoma from the TCGA immunologic Treatment cohort (https: / / xenabrowser.net / datapages / ?cohort=GDC%20TCGA%20Melanoma%20(SKCM)&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A443). In addition, we included 513 patients with lung adenocarcinoma (LUAD), 493 patients with lung squamous cell carcinoma (LUSC), 1082 patients with breast cancer, 406 patients with bladder cancer and 457 patients with melanoma from multi-cohort studies in TCGA. tumor patients. The data of each research patient includes all of its LncRNA gene expression, CTL expression, tumor microenvironment immune molecule expression and gene expression, and patient survival and prognosis information data.

[0039] 2. lncRNA screening

[0040]...

Embodiment 2

[0047] Verification analysis of embodiment 2 lncRNA in pan-tumor

[0048] For the data of other tumor patients we obtained above, including two groups of melanoma patients (70 cases and 457 cases), 513 cases of lung adenocarcinoma patients, 493 cases of lung squamous cell carcinoma patients, 1082 cases of breast cancer patients and 406 cases For patients with bladder cancer, the process of Example 1 was repeated for validation analysis. The results showed that it had prognostic significance in lung adenocarcinoma, bladder cancer and melanoma (lung adenocarcinoma: HR=0.75, 95% CI (0.57-0.99), P=0.038; bladder cancer: HR=0.68, 95% CI ( 0.51-0.92), P=0.011; melanoma: HR=0.62, 95% CI (0.47-0.81), P Figure 7 ). Therefore, the lncRNA and typing method have significance for anti-tumor immunotherapy efficacy and prognosis prediction of pan-tumor patients.

Embodiment 3

[0049] Example 3 Combined CTL (cytotoxic T lymphocyte) expression type

[0050] According to the current research, it is found that the expression of CTL is closely related to a variety of immune molecules, including a variety of immune cells, immune checkpoints and human leukocyte antigen (see Figure 8 ). Therefore, we tried to analyze the survival prognosis of multiple tumors including bladder cancer, lung adenocarcinoma, breast cancer, Her-2 positive breast cancer, and melanoma, and draw survival curves (such as Figure 9 ). The results showed that the expression of CTL was significantly correlated with the prognosis of patients, and compared with low expression of CTL, patients with high expression of CTL had a significant survival advantage.

[0051] Based on the above, we tried to combine lncRNA grouping and CTL expression to further stratify the bladder cancer patients in the TCGA cohort into four groups, including lncRNA functional type-high expression of CTL, lncRN...

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Abstract

The invention provides a group of long-chain non-coding RNA (lncRNA) markers for tumor immune typing, and the group of long-chain non-coding RNA markers totally comprises 49 lncRNAs. The invention also provides a tumor immune typing method based on the above lncRNA markers. According to the method, 49 lncRNAs are grouped and are combined with the expression quantity of cytotoxic T lymphocytes (CTL) to further classify patients into four groups, including an immune-active class, an immune-exclusion class, an immune-dysfunctional class and an immune-desert class by means of hierarchical clustering. The tumor immune subtype classification method provided by the invention has very strong correlation with prediction of the overall survival rate and the reactivity of anti-tumor immunotherapy, and has the characteristics of high objectivity, accuracy and repeatability. Establishment of the classification method provides a prediction index for the curative effect and the prognosis of the anti-immunotherapy of malignant tumor patients.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a tumor immunotyping method based on lncRNA markers. Background technique [0002] At present, tumor type, grade and stage are the final three indicators for evaluating tumor biological behavior and diagnosis, among which grade and stage are mainly used for evaluating the biological behavior and prognosis of malignant tumors. [0003] The pathological classification of malignant tumors is based on the degree to which the tumor cells are similar or close to normal tissues to their source tissues. The pathological classification of tumors is an important parameter that can best reflect the biological behavior and morphological characteristics of tumor-derived tissue cells. Tumors of different tissue types have different biological behaviors and invasion and metastasis capabilities. At present, the WHO tumor classification standard is a recognized tumor classification scheme,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C12N15/113
CPCC12Q1/6886C12Q2600/112C12Q2600/118C12Q2600/158C12Q2600/178
Inventor 姚和瑞宋尔卫余运芳区绮云张文达李岸霖
Owner SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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