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Application of plasma exosome biomarker in screening or curative effect prediction of gastric cancer neoadjuvant chemotherapy sensitive population

A biomarker, chemotherapy-sensitive technology, applied in the field of biomarkers, can solve the problems of inability to directly respond to tumor pathological changes, large patient damage, and difficult to achieve, and achieve the effect of promoting treatment strategies, high sensitivity, and convenient use.

Pending Publication Date: 2022-08-09
BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it remains to be verified whether the use of these molecular typing to guide treatment is beneficial to the clinical treatment of patients; moreover, obtaining enough samples from multiple endoscopic biopsies for molecular profiling is not only harmful to patients, but also expensive in clinical practice. hard to accomplish
[0005] In addition, previous studies mostly screened markers based on patient survival, which is affected by many factors and cannot directly reflect the pathological changes of tumors caused by treatment.
It is more direct and reliable to evaluate the treatment effect by evaluating tumor pathological response, but there are few related biomarkers at present. Exosomal biomarkers for the efficacy of adjuvant chemotherapy or screening drugs for gastric cancer therapy

Method used

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  • Application of plasma exosome biomarker in screening or curative effect prediction of gastric cancer neoadjuvant chemotherapy sensitive population
  • Application of plasma exosome biomarker in screening or curative effect prediction of gastric cancer neoadjuvant chemotherapy sensitive population
  • Application of plasma exosome biomarker in screening or curative effect prediction of gastric cancer neoadjuvant chemotherapy sensitive population

Examples

Experimental program
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Effect test

Embodiment 1

[0064] Example 1 Screening of exosomal RNAs related to the efficacy of neoadjuvant chemotherapy

[0065] 1. Include objects

[0066] We randomly selected 10 healthy volunteers and 20 patients with advanced gastric cancer (AGC) as the included subjects. The healthy volunteers were from Peking University First Hospital, and the gastric cancer patients were from the First Ward of the Gastrointestinal Cancer Center of Peking University Cancer Hospital. Both groups were 90% male, with a male-to-female ratio of 9:1; the mean age was 57 years, and the age range was 43-73 years. All 20 AGC patients received neoadjuvant chemotherapy with SOX (oxaliplatin-seggio) or XELOX (oxaliplatin-capecitabine) regimens (these two regimens are Chinese Society of Clinical Oncology (CSCO) guidelines). (2021 version) recommended regimen), the chemotherapy regimen is: oxaliplatin (130mg / m 2 ) administered intravenously on the first day, Sigiol (40-60 mg / m 2 ) or capecitabine (1000mg / m 2 ) was orall...

Embodiment 2

[0082] Example 2. Validation of exosomal RNA biomarkers associated with neoadjuvant chemotherapy efficacy

[0083]In order to further verify the predictive efficacy of exosomal RNAs, we comprehensively screened 18 exosomal RNAs with high differential multiples (specifically: 9 exosomal miRNAs (miR-27a-3p, miR-335-5p, -454-3p, miR-152-3p, miR-181a-5p, miR-1843, let-7i-5p, miR-130a-3p and miR-1307-3p), 5 exosomal mRNAs (LZIC, KMT2E , DAPP1, DAB2, and SRSF6) and 4 lncRNAs (lncPTMA-209, lncRMRP-202, lncRPS24-210, and lncFTH1-211)), using real-time quantitative PCR (qRT-PCR) in new independent 43 advanced gastric cancer patients validated in a patient cohort. The new 43 patients were also patients with advanced gastric cancer and received neoadjuvant chemotherapy with SOX or XELOX regimen and D2 gastric cancer resection, of which 19 patients had good response and 24 patients had poor response. The treatment method, curative effect standard, plasma collection method, exosome, and ...

Embodiment 3

[0093] Example 3 Construction and validation of exosomal RNA model related to the efficacy of neoadjuvant chemotherapy

[0094] To further explore better evaluation methods, we evaluated 8 exosomal RNAs (including 4 exosomal miRNAs: let-7i-5p, miR-1307-3p, miR-181a-5p and miR-181a) by Z-score method. -1843; 2 exosomal mRNAs: LZIC and SRSF6; and 2 exosomal lncRNAs: lncFTH1-211 and lncPTMA-209) were normalized for the expression of patients in the sequencing group and the validation group, and then multi-indicator Construction of the model.

[0095] Using the method of logistic regression, we firstly constructed two-molecular model group, three-molecular model group and four-molecular model group for the above 8 exosomes. There are 3 bimolecular models, 6 trimolecular models, and 2 tetramolecular models with values ​​greater than 0.80 (Table 4, Figure 5-7 ), and their AUCs in the training set were all greater than 0.90, indicating high specificity, sensitivity and stability...

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Abstract

The invention relates to plasma exosome mRNA, miRNA and / or lncRNA biomarkers and application of the plasma exosome mRNA, miRNA and / or lncRNA biomarkers in screening people sensitive to neoadjuvant chemotherapy of gastric cancer patients, predicting the curative effect of neoadjuvant chemotherapy and screening gastric cancer treatment drugs. According to the application disclosed by the invention, the fact that the plasma exosomes miRNAet-7i-5p, miR-1307-3p, miR-181a-5p and miR-1843, the plasma exosomes mRNA LZIC and SRSF6, and the plasma exosomes lncRNAncFTH1-211 and lncPTMA-209 are in-vivo key molecular characteristics of the gastric cancer patient in response to the neoadjuvant chemotherapy is determined for the first time. Before treatment, people sensitive to neoadjuvant chemotherapy of gastric cancer patients can be effectively screened only through a small amount of blood samples, the curative effect of neoadjuvant chemotherapy can be predicted, and implementation of optimized treatment strategies of the gastric cancer patients is greatly promoted.

Description

technical field [0001] The invention relates to the field of tumor molecular biology, in particular to a biomarker related to neoadjuvant therapy for gastric cancer and its application. Background technique [0002] About 42% of gastric cancers in the world occur in my country, of which about 71% are advanced gastric cancer (AGC). In recent years, the treatment mode of AGC has gradually changed from a single operation to a multidisciplinary comprehensive treatment based on surgery. Several studies have shown that for most advanced stage AGC, the perioperative treatment mode can further improve the survival of patients compared with the mode of standard radical resection combined with postoperative adjuvant chemotherapy. [0003] Neoadjuvant chemotherapy (NACT) is systemic chemotherapy performed before surgery. The purpose is to shrink the tumor, reduce tumor stage, provide drug sensitivity results for postoperative and remove undetected micrometastases, so as to facilitate ...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C12N15/113
CPCC12Q1/6886C12N15/113C12Q2600/106C12Q2600/136C12Q2600/158C12Q2600/178C12N2310/141
Inventor 季加孚李子禹唐小欢郭婷高翔宇邢晓芳陕飞
Owner BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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