Methods, systems, and applications for assessing the effectiveness of plasma treatment of tumors

Abstract

The application discloses a method and system for evaluating the effect of plasma treatment on tumor treatment and application. The method comprises the following steps: (1) obtaining the baseline level of an individual: obtaining the baseline expression level of ATF3 and / or DUSP1 in the tumor sample of a patient before plasma treatment as a first expression level; (2) obtaining the expression level after treatment: obtaining the expression level of ATF3 and / or DUSP1 in the tumor sample of the patient within a detection window period after plasma treatment as a second expression level; (3) up-regulation level evaluation: calculating the up-regulation amplitude of the second expression level relative to the first expression level, and evaluating the effect of plasma treatment according to the principle that the greater the up-regulation amplitude, the more obvious the treatment effect. The application can reliably evaluate the effect of plasma treatment on tumor treatment from the molecular level, thereby obtaining the effect data of plasma treatment on tumor treatment, which can be used in aspects such as analysis and clinical scheme optimization.

Description

Technical Field

[0001] This invention belongs to the field of tumor treatment technology, and more specifically, relates to a method, system, and application for evaluating the therapeutic effect of plasma therapy on tumors. Background Technology

[0002] Plasma is the fourth state of matter, independent of solid, liquid, and gas, and is mainly composed of electrons, ions, molecules, atoms, and a series of reactive free radicals. Over the past two decades, with the rapid development of atmospheric pressure plasma technology, its applications in the biomedical field have received increasing attention, gradually developing into a new discipline—"plasma medicine." Because plasma (also known as atmospheric pressure plasma, cryogenic plasma, or non-equilibrium plasma, abbreviated APP) can be generated in the atmosphere, it interacts with oxygen and nitrogen in the air to produce various reactive oxygen species (ROS) and reactive nitrogen species (RNS), among other reactive particles. Based on the oxidative / nitrifying stress effects of these reactive particles on cells and tissues, numerous studies by domestic and international institutions have confirmed the applications of plasma in sterilization, dermatology, tumor treatment, dentistry, and wound healing.

[0003] The application of plasma in tumor therapy is one of the hot topics in plasma biomedical research. Numerous studies have confirmed the inhibitory effects of plasma on various tumors, including those of the respiratory, digestive, epithelial and stromal, circulatory, immune, urinary, and nervous systems. While it is generally accepted that the active particles of plasma (including ROS and RNS) play a decisive role in its biomedical effects, the function of these active particles is dualistic. Relatively high doses of active particles can induce tumor cell apoptosis, but at lower concentrations, they may promote cell proliferation, damage repair, and cell protection, which is detrimental to tumor therapy.

[0004] The fundamental issue in the clinical application of plasma therapy is how to determine whether there is sufficient plasma treatment to induce tumor apoptosis, while avoiding the physiological protective effect on the tumor due to insufficient plasma treatment dosage.

[0005] Currently, the clinical application of plasma faces multiple bottlenecks: (1) Tumor heterogeneity: Tumors of different pathological types, and even tumors of the same type from different patients, have different cellular metabolic states, antioxidant capacity, and stress pathway response capabilities, resulting in huge differences in sensitivity to the same plasma treatment parameters. (2) Empirical nature of treatment parameters: At present, there is no standard dosimetric system for plasma therapy. Its treatment parameters (such as power, treatment time, and action distance) are mostly based on in vitro cell line experiments or empirical settings, lacking objective indicators that can reflect the biological characteristics of individual tumors to guide the personalized optimization of parameters. (3) Lagging effect assessment: At present, judging the effect of plasma therapy mainly relies on long-term postoperative imaging follow-up (observing whether recurrence occurs) or pathological examination (observing cell necrosis), which cannot accurately evaluate the effect of plasma, and therefore cannot accumulate effective data for clinical guidance and evaluation analysis.

[0006] Applying plasma therapy in clinical practice requires accumulating reliable testing data on the efficacy of plasma therapy, and currently there is a lack of methods for evaluating the efficacy of plasma therapy. Summary of the Invention

[0007] To address the aforementioned deficiencies or improvement needs of existing technologies, this invention provides a method, system, and application for evaluating the therapeutic effect of plasma therapy on tumors. The aim is to discover that ATF3 and DUSP1 genes are pan-cancer targets for plasma anti-tumor therapy, which can be used as biomarkers to quantify the efficacy of plasma therapy on tumors through their expression levels. This provides reliable data for clinical guidance of plasma therapy, supporting analysis and optimization of therapeutic parameters, thereby solving the current technical problem of lacking molecular-level efficacy evaluation data for plasma therapy on tumors.

[0008] To achieve the above objectives, according to one aspect of the present invention, a method for evaluating the efficacy of plasma therapy for tumors is provided, comprising the following steps:

[0009] (1) Obtain individual baseline levels: Obtain the baseline expression levels of ATF3 and / or DUSP1 in the patient's tumor sample before plasma therapy, as the first expression level, denoted as X;

[0010] (2) Obtaining the expression level after treatment: The expression level of ATF3 and / or DUSP1 in the patient's tumor sample during the detection window period after plasma treatment is obtained as the second expression level, denoted as Y;

[0011] (3) Upregulation level assessment: Calculate the upregulation magnitude of the second expression level relative to the first expression level, and assess the effect of plasma therapy according to the principle that the greater the upregulation magnitude, the more obvious the treatment effect.

[0012] Preferably, in the method for verifying the efficacy of plasma therapy for tumors, the detection window time period in step (2) is a time window in which the upregulation of the marker can be stably detected, preferably within 96 hours after treatment, and more preferably within 24 hours.

[0013] Preferably, the method for verifying the efficacy of plasma therapy for tumors assesses the effectiveness of plasma therapy for the patient's biological effects when a statistically significant upregulation of the expression levels of ATF3 and / or DUSP1 is detected; the expression levels are protein expression levels or mRNA expression levels.

[0014] Preferably, in the method for verifying the efficacy of plasma therapy for tumors, the statistically significant upregulation criteria for the expression levels of ATF3 and / or DUSP1 include: the logarithm of the differential expression fold (log2FC) is greater than 1, and log2FC = log2(Y / X).

[0015] According to another aspect of the present invention, a system for evaluating the efficacy of plasma therapy for tumors is provided, comprising a transcriptional information acquisition module, an upregulation level assessment module, and an evaluation module;

[0016] The information acquisition module is used to acquire the baseline expression level of ATF3 and / or DUSP1 in the patient's tumor sample before plasma therapy, as the first expression level, denoted as X; and to acquire the post-treatment expression level of ATF3 and / or DUSP1 in the patient's tumor sample during the detection window period after plasma therapy, as the second expression level, denoted as Y.

[0017] The first expression level X and the second expression level Y are then submitted to the evaluation module.

[0018] The upregulation level assessment module is used to calculate the upregulation magnitude of the second expression level relative to the first expression level, and provide the upregulation magnitude to the assessment module;

[0019] The evaluation module is used to assess the effectiveness of plasma therapy based on the magnitude of the increase, following the principle that the greater the increase, the more obvious the treatment effect.

[0020] Preferably, in the system for evaluating the efficacy of plasma therapy for tumors, the detection window period is a time window in which the upregulation of biomarkers can be stably detected, preferably within 96 hours after treatment, and more preferably within 24 hours.

[0021] Preferably, the system for evaluating the efficacy of plasma therapy for tumors assesses the biological effect of plasma therapy on the patient as effective when a statistically significant upregulation of the expression levels of ATF3 and / or DUSP1 is detected; the expression levels are protein expression levels or mRNA expression levels.

[0022] Preferably, in the system for evaluating the efficacy of plasma therapy for tumors, the statistically significant upregulation criteria for the expression levels of ATF3 and / or DUSP1 include: the logarithm of the differential expression fold (log2FC) is greater than 1, and log2FC = log2(Y / X).

[0023] According to another aspect of the invention, the use of ATF3 and / or DUSP1 expression level detection reagents in the preparation of a detection kit for evaluating the efficacy of plasma therapy for tumors is provided.

[0024] Preferably, in the application, the ATF3 and / or DUSP1 expression level detection reagent is an mRNA expression level detection reagent or a protein expression level detection reagent.

[0025] In summary, compared with the prior art, the above-described technical solutions conceived by this invention can achieve the following beneficial effects:

[0026] This invention first uses bioinformatics methods and experiments to verify that ATF3 and DUSP1 genes are pan-cancer targets of plasma, and determines that the therapeutic effect of plasma is positively correlated with the upregulation of ATF3 and DUSP1 genes. By using the upregulation of ATF3 and / or DUSP1 gene expression levels, the efficacy of plasma therapy for tumors can be reliably evaluated at the molecular level, thereby obtaining efficacy data of plasma therapy for tumors for analysis, clinical protocol optimization, etc. Attached Figure Description

[0027] Figure 1 This involves intersection analysis of differentially expressed genes from 5 datasets.

[0028] Figure 2 This is a diagram showing the inhibitory effect of plasma treatment on the proliferation of pituitary tumor cell lines;

[0029] Figure 3 The effects of plasma treatment on the expression of ATF3 and DUSP1 in GH3 cells;

[0030] Figure 4 This is the result of a human validation experiment on plasma treatment of pituitary tumors. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0032] While studies have explored the various biological effects of plasma on tumor cells, the therapeutic efficacy of plasma cannot be evaluated through biochemical testing. This invention addresses the problem of quantitative evaluation and individualized optimization of plasma therapy for tumors. The core idea is to discover and validate molecular biomarkers that specifically and stably reflect the core biological effects induced by plasma. By quantitatively detecting changes in the physiological and biochemical indicators of these biomarkers, objective evidence is provided for efficacy assessment and optimization of treatment parameters, thus achieving a leap from "empirical" to "precision" plasma therapy. Currently, no universally applicable biomarkers reflecting the effects of plasma have been discovered.

[0033] This invention, through in-depth bioinformatics analysis and experimental verification, is the first to discover and confirm that transcription factor ATF3 and its downstream target DUSP1 exhibit significant and consistent upregulation in various types of tumor cells in response to APP treatment. Experiments have confirmed that this upregulation is closely related to APP-induced cellular stress and apoptosis pathway activation, making it a reliable molecular marker for indicating whether APP treatment has successfully elicited the expected biological effects.

[0034] This invention provides a method for evaluating the efficacy of plasma therapy for tumors, the core of which lies in using ATF3 and / or DUSP1 as efficacy indicators. A typical implementation of this method includes the following steps:

[0035] (1) Obtain individual baseline levels: Obtain the baseline expression levels of ATF3 and / or DUSP1 in the patient's tumor sample (such as preoperative puncture biopsy tissue) before plasma therapy, as the first expression level, denoted as X;

[0036] (2) Obtain the expression level after treatment: The expression level of ATF3 and / or DUSP1 in the patient's tumor sample after plasma treatment within the detection window period is taken as the second expression level and denoted as Y; the detection window period is the time window in which the upregulation of the marker can be stably detected, generally within 96 hours after treatment, typically within 24 hours after treatment.

[0037] (3) Upregulation level assessment: Calculate the upregulation magnitude of the second expression level relative to the first expression level, and assess the effect of plasma therapy according to the principle that the greater the upregulation magnitude, the more obvious the treatment effect. Specifically:

[0038] When a statistically significant upregulation of ATF3 and / or DUSP1 expression levels is detected, the biological effect of plasma therapy on the patient is assessed as effective; the expression levels are either protein expression levels or mRNA expression levels.

[0039] The statistically significant upregulation criteria for the expression levels of ATF3 and / or DUSP1 include: the logarithm of the differential expression fold (log2FC) is greater than 1, and log2FC = log2(Y / X), i.e., upregulation to 2-fold; the preferred criteria for the statistically significant upregulation of the expression levels of ATF3 and / or DUSP1 also include: a statistical significance test p-value < 0.05 when the number of biological replicates n ≥ 3.

[0040] This method for evaluating the efficacy of plasma therapy for tumors can be applied clinically to guide the optimization of plasma therapy protocols: by comparing the upregulation of biomarkers induced by different APP treatment parameters (such as power and time), the relative efficacy of each parameter can be quantitatively assessed, thereby selecting the optimal treatment protocol for individual patients.

[0041] In this invention, the expression levels of ATF3 and DUSP1 can be detected by conventional techniques in the art, which can be used to detect the mRNA content of gene transcription or the protein content of gene expression.

[0042] The significant advantages of this invention are:

[0043] (1) Universality of the marker: Experimental data confirm that the upregulation of ATF3 and DUSP1 is a common downstream event in various plasma operating modes (such as different working gases and discharge parameters). Therefore, the evaluation method based on this marker has broad applicability and does not depend on a specific plasma device configuration.

[0044] (2) Personalization potential of the method: By comparing the “pre-treatment baseline-post-treatment response” model, the method of the present invention can effectively avoid the interference of differences in the genetic background between individuals and directly measure the net biological effect of APP on the tumor of a specific patient, laying the foundation for achieving true personalized precision treatment.

[0045] (3) Prospective clinical translation: The core logic of “molecular marker response” established in this invention provides a clear biological basis and feasible technical path for the future development of faster intraoperative detection technology and intelligent treatment system with integrated real-time feedback.

[0046] The system for evaluating the efficacy of plasma therapy for tumors provided by this invention includes a transcriptional information acquisition module, an upregulation level assessment module, and an evaluation module;

[0047] The information acquisition module is used to acquire the baseline expression level of ATF3 and / or DUSP1 in the patient's tumor sample before plasma therapy, as the first expression level, denoted as X; and to acquire the post-treatment expression level of ATF3 and / or DUSP1 in the patient's tumor sample during the detection window period after plasma therapy, as the second expression level, denoted as Y.

[0048] The first expression level X and the second expression level Y are then submitted to the evaluation module.

[0049] The detection window period is the time window during which the upregulation of the marker can be stably detected, preferably within 96 hours after treatment, and more preferably within 24 hours.

[0050] The upregulation level assessment module is used to calculate the upregulation magnitude of the second expression level relative to the first expression level, and provide the upregulation magnitude to the assessment module;

[0051] The evaluation module is used to assess the effectiveness of plasma therapy based on the magnitude of the increase, following the principle that the greater the increase, the more obvious the treatment effect.

[0052] When a statistically significant upregulation of ATF3 and / or DUSP1 expression levels is detected, the biological effect of plasma therapy on the patient is assessed as effective; the expression levels are either protein expression levels or mRNA expression levels.

[0053] When a statistically significant upregulation of ATF3 and / or DUSP1 expression levels is detected, the biological effect of plasma therapy on the patient is assessed as effective; the expression levels are either protein expression levels or mRNA expression levels.

[0054] The following is an example:

[0055] Example 1: ATF3 and DUSP1 can serve as biomarkers for the inhibitory effect of plasma on tumors.

[0056] First, datasets related to plasma-induced tumor cell apoptosis studies were selected from databases such as GEO, resulting in four datasets (GSE59997, GSE76022, PRJCA000445, and GSE119052). These four datasets underwent quality control and standardization, and the transcriptomic differences induced by the control and plasma-treated tumor cell groups in each dataset were compared. Additionally, a dataset, GSE178148, on the effects of plasma on organoids was included. In this dataset, the direct effect of plasma is also oxidative stress damage, similar to the effect of plasma on tumors. Differentially expressed genes were screened based on an absolute value of log2FC (logarithmic fold change in DEGs between groups) greater than 1 and a P-value < 0.05. After taking the intersection of differentially expressed genes from these five datasets, ATF3 and DUSP1 were found to be differentially expressed, both showing an upregulation trend. Figure 1 ,in Figure 1 Figure A shows the intersection of the gene sets to obtain two genes, ATF3 and DUSP1, which are both upregulated. Figure 1 Figure B shows genes that were not commonly downregulated when the intersection of gene sets was taken; however, no commonly downregulated genes were found when the intersection of differentially regulated genes in the datasets was taken. This suggests that ATF3 and DUSP1 may be two important pan-cancer targets of plasma and could serve as biomarkers of plasma biological effects, which is crucial for studying the mechanisms by which plasma induces cell damage.

[0057] Simultaneously, GO and KEGG functional annotations (clusterProfilerv4.14.4) were performed on high-frequency differentially expressed genes (i.e., differentially expressed genes repeated in three or more datasets). The results showed that these differentially expressed genes were significantly enriched in the MAPK signaling pathway, and also involved in the IL-17 and TNF signaling pathways. GO analysis indicated that these differentially expressed genes are mainly involved in biological processes such as DNA-binding transcription promoter activity, MAP enzyme phosphorylase activity, and positive regulation of apoptosis signaling, with the positive regulation of apoptosis (GO:0043065) showing the highest significance (p=6.11×10⁻⁹). These data suggest that APP may activate apoptosis signaling pathways by regulating the expression of ATF3 and DUSP1. Figure 1 To analyze the intersection of differentially expressed genes in five datasets of plasma-induced apoptosis and perform pathway enrichment analysis, the following steps were taken. Figure 1 Figures A and B show that taking the intersection of the differentially expressed genes in each dataset yields two genes, ATF3 and DUSP1, that are both upregulated.

[0058] Example 2: Plasma upregulates the expression of ATF3 and DUSP1 and inhibits GH3 activity.

[0059] The GH3 pituitary adenoma cell line was directly treated using a plasma jet device developed by our research group (Journal of Physics D: Applied Physics, 2017, 50(9): 095401). After treatment, the GH3 cells were cultured for 24-96 hours and observed. Cell viability was detected using the CCK-8 assay. The results showed that the cell viability of the control group gradually increased with prolonged culture time, while plasma treatment significantly inhibited the viability of GH3 cells. Figure 2 ). Figure 2 The effect of plasma treatment on the proliferation of pituitary tumor cell lines was observed. n=3, **P<0.01, ***P<0.001 compared with the untreated control group.

[0060] Based on this, we subjected GH3 cells in six-well plates to plasma treatment and extracted RNA and proteins. The expression levels of ATF3 and DUSP1 in GH3 cells were then detected using qRT-PCR and Western blot techniques, respectively. The qRT-PCR primer sequences are shown in Table 1. Mouse anti-ATF3 and DUSP1 antibodies were purchased from Santa Cruz Biotechnology, USA. The results showed that compared with the control group, the mRNA levels and protein expression of ATF3 and DUSP1 gradually increased with prolonged plasma treatment time, reaching the highest expression level after 360 seconds of APP treatment. Figure 3 (Figure A). This part of the results indicates that ATF3 and DUSP1 are important markers of plasma interaction and are closely related to the biological effects of plasma.

[0061] Table 1. qRT-PCR primers for ATF3 and DUSP1.

[0062]

[0063] Effects of plasma treatment on the expression of ATF3 and DUSP1 in GH3 cells, such as Figure 3 As shown, where Figure 3 Figure A shows the changes of ATF3 and DUSP1 at the mRNA transcription level. Figure 3 Figure B shows the changes in protein expression levels of ATF3 and DUSP1; Figure 3 Figure C shows the quantitative analysis of each protein; n=3, **P<0.01, ***P<0.001, ****P<0.0001.

[0064] Example 3: Verification of the effect of plasma on clinically derived primary pituitary tumor cells

[0065] To further confirm the inhibitory effect of plasma on pituitary tumors, we included two patients with invasive pituitary adenomas (Knosp IV, Hardy II, stage D) diagnosed by the Department of Neurosurgery at Beijing Tiantan Hospital. Figure 4 Primary cell cultures were performed using surgically removed tumor tissue, followed by plasma treatment under the same conditions. Results showed that plasma treatment conditions associated with ATF3 and DUSP1 expression had a good inhibitory effect on these two primary pituitary tumor cell lines. The effects of plasma treatment on patient-derived primary pituitary tumor cells were as follows: Figure 4 As shown, (a) the primary cell isolation and culture process, (b) the patient's magnetic resonance imaging and case diagnosis results, and (c) CCK-8 assay showing the inhibition of primary pituitary tumor cell activity by plasma. n=3, **P<0.01, ***P<0.001 compared with the untreated control group.

[0066] Example 4: The Relationship Between the Effects of Plasma and Processing Parameters and Conditions

[0067] Currently, there is a lack of consensus on plasma treatment methods and working conditions. The plasma discharge structures vary widely; the conditions for plasma generation and treatment are complex, such as using air, helium, argon, or various mixed gases to generate plasma; as for treatment methods, some plasmas directly treat tumors, while others indirectly treat tumors using plasma activation liquids, activation gels, or activation ice and other activation medium materials. Although all of these methods can induce tumor death, there is no fair understanding of whether different discharge structures, working gases, and treatment methods have comparable therapeutic effects or how to evaluate the therapeutic effects.

[0068] We used the dataset from Example 1 to screen for high-frequency differentially expressed genes and performed GO and KEGG functional annotation. GO and KEGG enrichment analysis revealed that the differentially expressed genes were mainly enriched in pathways related to tumor proliferation, such as the MAPK signaling pathway, the IL-17 signaling pathway, and the TNF signaling pathway (P<0.05). Further gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) ​​were used to investigate the activation status of these signaling pathways in tumor cells after plasma treatment.

[0069] We further employed the GSVA scoring method to analyze the differences between the plasma treatment group and the control group, the direct treatment group and the indirect treatment group, and the group using rare gases (such as He / Ar) or air as the working gas. This invention calculated the GSVA score differences for 20 significantly different pathways (10 upregulated and 10 downregulated) selected from the primary or secondary conditions (rare gas vs. air, direct vs. indirect treatment) (see Tables 2-3).

[0070] Table 2. Comparison of GSVA scores (PValue) of plasma treatment on upregulated KEGG pathways

[0071]

[0072] Table 3. Comparison of GSVA scores (PValue) of plasma treatment on upregulated KEGG pathways

[0073]

[0074] The results showed that significant differences in scores were observed between the treatment and control groups among the top 20 signaling pathways with significant differences. However, no significant differences were found in pathway scores caused by the working gas (rare gas and air) or the mode of action (direct versus indirect treatment) of the plasma. The experimental data in this study confirm that the efficacy of plasma therapy is only related to whether plasma treatment is used, and is unrelated to other secondary factors such as discharge conditions, working gas, and treatment method. Plasma inhibits cancer by upregulating the expression levels of pan-cancer target genes ATF3 and DUSP1. ATF3 and DUSP1 are pan-cancer targets of plasma; as long as changes in the expression levels of ATF3 and DUSP1 are detected, this method can be applied to evaluate the efficacy of plasma treatment for cancer treatment regardless of discharge conditions, working gas, or treatment method.

[0075] In summary, we first performed quality control and bioinformatics analysis on the sequencing data of the control and plasma-treated groups in the enrolled datasets. Based on the five enrolled datasets (GSE59997, GSE76022, PRJCA000445, GSE178148, and GSE119052), we identified two pan-cancer targets of plasma, ATF3 and DUSP1. These genes were upregulated in all five plasma-treated groups, suggesting that they may be closely related to the effects of plasma. We experimentally verified the upregulation of mRNA and protein expression of these two genes after plasma treatment. Furthermore, based on bioinformatics analysis, we found that factors such as the working gas and treatment method of the plasma had no significant impact on its effectiveness. We then validated the effects of plasma and its influence on the expression of ATF3 and DUSP1 in a common intracranial pituitary tumor. Based on this, we optimized the plasma treatment conditions and used these conditions to verify its inhibitory effect on clinically derived primary pituitary tumor cells.

[0076] These studies demonstrate that ATF3 and DUSP1 can indirectly reflect the treatment effect of plasma, assist in the optimization of plasma treatment parameters, and can be used in the treatment of clinical tumors to inhibit tumor activity.

[0077] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A system for evaluating the efficacy of plasma therapy for pituitary tumors, characterized in that, It includes a transcription information acquisition module, an upregulation level assessment module, and an evaluation module; The information acquisition module is used to acquire the baseline expression level of ATF3 and / or DUSP1 in the patient's tumor sample before plasma therapy, as the first expression level, denoted as X; and to acquire the post-treatment expression level of ATF3 and / or DUSP1 in the patient's tumor sample within the detection window time period after plasma therapy, as the second expression level, denoted as Y; the detection window time period is the time window in which the upregulation of the marker can be stably detected, which is within 96 hours after treatment; The first expression level X and the second expression level Y are then submitted to the evaluation module. The upregulation level assessment module is used to calculate the upregulation magnitude of the second expression level relative to the first expression level, and provide the upregulation magnitude to the assessment module; The evaluation module is used to assess the efficacy of plasma therapy based on the upregulation magnitude, following the principle that the greater the upregulation magnitude, the more significant the therapeutic effect. When a statistically significant upregulation of ATF3 and / or DUSP1 expression levels is detected, the biological effect of plasma therapy on the patient is assessed as effective. The criteria for a statistically significant upregulation of ATF3 and / or DUSP1 expression levels include: the logarithm of the differential expression fold (log2FC) is greater than 1, and log2FC = log2(Y / X).

2. The system for evaluating the efficacy of plasma therapy for pituitary tumors as described in claim 1, characterized in that, The expression level refers to either the protein expression level or the mRNA expression level.

3. Application of ATF3 and / or DUSP1 expression level detection reagents in the preparation of a detection kit for evaluating the efficacy of plasma therapy for pituitary tumors.

4. The application as described in claim 3, characterized in that, The ATF3 and / or DUSP1 expression level detection reagent is an mRNA expression level detection reagent or a protein expression level detection reagent.

Images