System for predicting benefit of adjuvant chemotherapy of small cell lung cancer and identifying chemotherapy drug-resistant treatment target and application

A technology for small cell lung cancer and prognosis, applied in the field of biomedicine, can solve problems such as unclear research, and achieve the effect of improving treatment efficacy

Pending Publication Date: 2021-12-07
CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The abnormality of m6A regulatory elements is closely related to metastasis and abnormal prognosis, but its regulatory mechanism and role in small cell lung cancer, especially chemotherapy resistance, are not clear at present

Method used

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  • System for predicting benefit of adjuvant chemotherapy of small cell lung cancer and identifying chemotherapy drug-resistant treatment target and application
  • System for predicting benefit of adjuvant chemotherapy of small cell lung cancer and identifying chemotherapy drug-resistant treatment target and application
  • System for predicting benefit of adjuvant chemotherapy of small cell lung cancer and identifying chemotherapy drug-resistant treatment target and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] Example 1. Prediction of curative effect of adjuvant chemotherapy for small cell lung cancer and application of drug resistance targets

[0089]Download the GSE40275 cohort from the GEO database (https: / / www.ncbi.nlm.nih.gov / geo / ) as a training cohort for constructing small cell lung cancer prediction models; Lin-fixed paraffin-embedded FFPE tissues served as a validation cohort and an independent cohort for model validation. The clinical characteristics of all patients are shown in Table 1.

[0090] Table 1 Clinical characteristics of patients with small cell lung cancer

[0091]

[0092] Note: NA means not available

[0093] In both the validation cohort and the independent cohort, the inclusion criteria for small cell lung cancer patients were as follows: 1) The patient was diagnosed with small cell lung cancer by the National Cancer Center; 2) The patient’s diagnosis and treatment information was complete; 3) The patient did not receive neoadjuvant therapy befo...

Embodiment 2

[0255] Example 2. Identification of drug-resistant targets for adjuvant chemotherapy in patients with small cell lung cancer

[0256] Select the genes with a coefficient >1 in the prediction model in Example 1—ZCCHC4, METTL5, G3BP1, and RBMX—to explore their mechanism of action in chemotherapy resistance, and identify the target genes of chemotherapy resistance.

[0257] 1. Expression of candidate genes in small cell lung cancer

[0258] Comparing the expression of candidate genes in small cell lung cancer tissue and normal tissue, the results showed that all candidate genes were highly expressed in tumor tissue (P Figure 18 )

[0259] 2. Knock down expression of candidate genes

[0260] The candidate gene was knocked down by transient cell transfection technology, as follows:

[0261] siRNA transfection reagent adopts life technologies TM Lipofectamine RNAiMAX Reagent. The siRNAs targeting ZCCHC4, METTL5, G3BP1 and RBMX genes were siRNAs of siZCCHC4, siMETTL5, siG3BP1 and...

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Abstract

The invention discloses a system for predicting benefit of adjuvant chemotherapy of small cell lung cancer and identifying chemotherapy drug-resistant treatment targets and application. The invention provides an application of ZCCHC4, IGF2BP3, ALKBH5, YTHDF3, METTL5, G3BP1 and RBMX genes as markers in preparation of a product for predicting prognosis of a small cell lung cancer patient. According to the invention, the importance of m6A modification in SCLC is proved, a prediction model for predicting chemotherapy benefits is established, potential treatment targets of small cell lung cancer chemotherapy drug resistance are identified, and the treatment targets are closely related to drug resistance. And further prospective verification on inhibition of tumor growth and tumor chemotherapy drug resistance by the m6A regulating element is beneficial to improvement of the treatment effect of clinical small cell lung cancer.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a system and application for predicting the benefit of adjuvant chemotherapy for small cell lung cancer and identifying targets for chemotherapy-resistant treatment. Background technique [0002] Small cell lung cancer (SCLC) is a highly lethal high-grade neuroendocrine tumor characterized by short doubling time, rapid growth, and early metastatic spread. SCLC accounts for approximately 15% of lung cancers and has a five-year survival rate of less than 7%. Despite the continuous development of new therapeutic measures such as molecular targeted drugs and immune checkpoint inhibitors, there has been no significant breakthrough in the treatment strategies for patients with small cell lung cancer in recent decades, and chemotherapy is still an irreplaceable first-line treatment for patients with small cell lung cancer . However, most SCLC patients rapidly develop drug resistance after t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574G16B15/30G16B20/00G16B40/00G16H50/50A41D31/08A61K45/00A61K45/06A61K31/713A61K33/243A61P35/00
CPCC12Q1/6886G01N33/57423G01N33/57484G16B15/30G16B20/00G16B40/00G16H50/50A41D31/08A61K45/00A61K45/06A61K31/713A61K33/243A61P35/00C12Q2600/118C12Q2600/158C12Q2600/106C12Q2600/136A61K2300/00
Inventor 赫捷孙楠张志慧张超奇张国超
Owner CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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