CN114085910A - Diffuse large B cell lymphoma prognosis model based on MYC/BCL2 dual expression and immune microenvironment, application and prognosis method - Google Patents
Diffuse large B cell lymphoma prognosis model based on MYC/BCL2 dual expression and immune microenvironment, application and prognosis method Download PDFInfo
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Abstract
The invention discloses a diffuse large B cell lymphoma prognosis model based on MYC/BCL2 double expression and immune microenvironment, application and a prognosis method. Based on MYC/BCL2 protein expression level and immune microenvironment, the invention has unique function in prognosis of various DLBCL subtype patients by cooperation of the MYC/BCL2 protein expression level and the immune microenvironment, assists clinicians in judging clinical development and disease outcome of the patients, and realizes accurate layered treatment.
Description
Technical Field
The invention belongs to the technical field of biological and medical examination, and particularly relates to a diffuse large B cell lymphoma prognosis model based on MYC/BCL2 double expression and immune microenvironment, application and a prognosis method.
Background
Diffuse Large B-Cell Lymphoma (DLBCL) is currently the most common adult non-hodgkin Lymphoma, a tumor that is highly aggressive and grows rapidly. Research shows that DLBCL has high heterogeneity in aspects of pathological morphology, immunological phenotype, gene expression and the like, and more evidences show that the DLBCL may not be a truly independent disease species.
The traditional method for evaluating the prognosis of DLBCL patients mainly depends on clinical parameters, and the most commonly used is the International Prognostic Index (IPI), which comprises 5 clinical characteristics such as age, functional state, serum lactate dehydrogenase level, number of accumulated outer bits and AnNarbor stage. Since this evaluation is only a combination of clinical criteria, it does not reflect well the molecular biological characteristics inherent in tumorigenesis. The prognosis of a significant proportion of patients cannot be accurately assessed and presents a completely different survival situation.
In recent years, studies based on gene expression profiles have greatly increased the awareness of DLBCL, and have also enabled further classification, diagnosis and prognosis at the molecular level. In the molecular aspect, DLBCL has been subjected to various studies to report its relevant molecular characteristics. There is a gene rearrangement of DLBCL of about 3/4, and BCL2, BCL6, MYC, etc. belong to the typical rearranged genes of DLBCL. Overall, detection at the molecular level is of great significance for the overall diagnostic assessment of DLBCL.
With the application of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone), the total survival rate of DLBCL can reach 60%, the clinical curative effect of DLBCL is increasingly improved, but patients still have ineffective treatment or relapse rapidly after treatment, the disease progresses rapidly, and the prognosis is poor.
Therefore, the research on the biological characteristics of different subtypes of DLBCL has important theoretical significance and clinical value for making corresponding treatment schemes, and has immeasurable social value.
Disclosure of Invention
The invention aims to solve the technical problems and provides a diffuse large B cell lymphoma prognosis model based on MYC/BCL2 double expression and immune microenvironment, application and a prognosis method.
In order to solve the problems, the invention is realized according to the following technical scheme:
in a first aspect, the invention provides a diffuse large B-cell lymphoma prognosis model based on MYC/BCL2 dual expression and immune microenvironment, which assesses prognostic risk in patients with different diffuse large B-cell lymphoma subtypes based on protein expression levels and tumor immune cell infiltration levels of MYC and BCL 2.
In combination with the first aspect, the present invention also provides embodiment 1 of the first aspect, in particular, the tumor immune cell infiltration degree includes infiltration degrees of NK cells, T cells and macrophages.
In combination with the first aspect, the invention also provides embodiment 2 of the first aspect, in particular, the patients with diffuse large B-cell lymphoma subtype patients comprise EZB subtype, MCD subtype, ST2 subtype, BN2 subtype and LymphGen unclassified subtype.
With reference to the first aspect, the present invention also provides embodiment 3 of the first aspect, in particular, the prognostic indicator of the prognostic model for the EZB subtype, wherein protein expression levels of MYC and BCL2 of not less than 70% are prognostic liability factors; the infiltration degree CD56+ NK cells > 3% of NK cells is a favorable factor for prognosis;
the prognosis index of the prognosis model to MCD subtype, the infiltration degree CD8+ T cells of T cells is more than or equal to 5% as a prognosis favorable factor;
for the prognosis indexes of the ST2 subtype of the prognosis model, the infiltration degree T cells of T cells is more than or equal to 24.5%, the infiltration degree Macrophages of Macrophages is more than or equal to 8.8%, and the infiltration degree NK cells of NK cells is more than or equal to 2.9% are poor prognosis factors;
for the prognosis indexes of the prognosis model for the BN2 subtype, protein expression levels of MYC and BCL2 are more than or equal to 70% and are poor prognosis factors, and infiltration degrees of T cells, namely CD4+ T cells, are more than or equal to 12.9% and are favorable prognosis factors;
the prognostic index of the prognostic model to the unclassified subtype of LymphGen is characterized in that the protein expression level of MYC and BCL2 is more than or equal to 70%, the infiltration degree CD56+ NK cells of NK cells is more than or equal to 12.3% and is a prognostic favorable factor, the infiltration degree CD8+ T of T cells is more than or equal to 17.4%, and the infiltration degree Macrophages of Macrophages is less than or equal to 20% and is a prognostic unfavorable factor.
In combination with the first aspect, the present invention also provides the 4 th embodiment of the first aspect, in particular, the prognostic model is established by the following method:
acquiring sample data of a patient with diffuse large B cell lymphoma receiving standard immunochemistry, and performing gene deep sequencing and FISH analysis on tumor-related genes to obtain a gene deep sequencing result and a FISH analysis result;
classifying patients with diffuse large B-cell lymphoma subtype into EZB subtype, MCD subtype, ST2 subtype, BN2 subtype and LymphGen unclassified subtype by adopting a LymphGen typing system;
based on different diffuse large B cell lymphoma subtypes, carrying out relationship risk aiming at the protein expression levels of MYC and BCL2 and prognosis to obtain prognostic indicators of the protein expression levels of MYC and BCL2 in different subtypes;
protein expression of related biomarkers is analyzed through multicolor immunofluorescence histochemistry, diffuse large B cell lymphoma patient samples of different genetic subtypes are compared, and the comparison result obtains that immunity microenvironments of a BN2 subtype and a LymphGen unclassified subtype are more active than those of an MCD subtype, an EZB subtype and an ST2 subtype;
and (3) carrying out relation analysis on T cells, macrophages and NK cells and prognosis to obtain a prognostic index of the tumor immune cell infiltration degree.
In a second aspect, the invention also provides the use of a prognostic model for diffuse large B-cell lymphoma based on MYC/BCL2 dual expression and immune microenvironment for assessing prognostic risk in patients with diffuse large B-cell lymphoma of EZB subtype, MCD subtype, ST2 subtype, BN2 subtype, and LymphGen unclassified subtype.
In a third aspect, the invention also provides a diffuse large B-cell lymphoma prognosis method based on MYC/BCL2 dual expression and immune microenvironment, comprising the following steps:
obtaining tumor tissues of a patient with diffuse large B cell lymphoma, performing gene deep sequencing and FISH (fluorescence in situ hybridization) detection on lymphoma related genes, and determining the subtype of the patient with diffuse large B cell lymphoma;
immunohistochemical detection is carried out on the tumor tissue, fluorescence multiplex immunohistochemical detection of 13 immune cell markers is carried out, and the protein expression level of MYC and BCL2 and the infiltration degree of tumor immune cells are detected;
the patient prognostic risk is assessed based on a prognostic model that assesses prognostic risk in patients with different diffuse large B-cell lymphoma subtypes based on protein expression levels of MYC and BCL2 and the degree of tumor immune cell infiltration.
With reference to the third aspect, the present invention further provides a 1 st preferred embodiment of the third aspect, specifically:
the prognostic indicators of the prognostic model to the EZB subtype, wherein the protein expression levels of MYC and BCL2 are more than or equal to 70 percent as poor prognostic factors; the infiltration degree CD56+ NK cells > 3% of NK cells is a favorable factor for prognosis;
the prognosis index of the prognosis model to MCD subtype, the infiltration degree CD8+ T cells of T cells is more than or equal to 5% as a prognosis favorable factor;
for the prognosis indexes of the ST2 subtype of the prognosis model, the infiltration degree T cells of T cells is more than or equal to 24.5%, the infiltration degree Macrophages of Macrophages is more than or equal to 8.8%, and the infiltration degree NK cells of NK cells is more than or equal to 2.9% are poor prognosis factors;
for the prognosis indexes of the prognosis model for the BN2 subtype, protein expression levels of MYC and BCL2 are more than or equal to 70% and are poor prognosis factors, and infiltration degrees of T cells, namely CD4+ T cells, are more than or equal to 12.9% and are favorable prognosis factors;
the prognostic index of the prognostic model to the unclassified subtype of LymphGen is characterized in that the protein expression level of MYC and BCL2 is more than or equal to 70%, the infiltration degree CD56+ NK cells of NK cells is more than or equal to 12.3% and is a prognostic favorable factor, the infiltration degree CD8+ T of T cells is more than or equal to 17.4%, and the infiltration degree Macrophages of Macrophages is less than or equal to 20% and is a prognostic unfavorable factor.
Compared with the prior art, the invention has the beneficial effects that:
the research of the invention finds that MYC/BCL2 protein expression level and immune microenvironment have unique functions in the aspect of prognosis of various DLBCL subtype patients in cooperation, and assists clinicians in judging clinical development and disease outcome of the patients to realize accurate layered treatment.
Drawings
Embodiments of the invention are described in further detail below with reference to the attached drawing figures, wherein:
FIG. 1 is that the dual high expression of MYC/BCL2 of the present invention has a significant adverse effect on Overall Survival (OS) of the EZB subtype;
FIG. 2 is that the double high expression of MYC/BCL2 of the present invention has a significant adverse effect on progression-free survival (PFS) of the BN2 subtype;
FIG. 3 is a graph showing that dual high expression of MYC/BCL2 of the present invention has a significant adverse effect on OS (left panel) and PFS (right panel) of the unclassified subtype of LymphGen;
FIG. 4 is a graph showing that NK cell infiltration of the present invention has a significant beneficial effect on OS of EZB subtype;
FIG. 5 is a graph showing that T cell infiltration of the present invention has a significant beneficial effect on OS of the MCD subtype;
FIG. 6 is a graph showing that T cell infiltration (A), macrophage infiltration (B) and NK cell infiltration (C) of the present invention all have significant adverse effects on OS at subtype ST 2;
FIG. 7 is a significant beneficial effect of T cell infiltration of the present invention on PFS of the BN2 subtype;
FIG. 8 is a graph showing that T cell infiltration (A), macrophage infiltration (B) of the present invention have a significant adverse effect on OS of the unclassified subtype of LymphGen; NK cell infiltration (C) had a significant beneficial effect on OS of the unsorted subtype of LymphGen.
Detailed Description
The preferred embodiments of the present invention will be described in conjunction with the accompanying drawings, and it will be understood that they are described herein for the purpose of illustration and explanation and not limitation.
The present invention relates to the noun explanation:
DLBCL (Diffuse Large B-Cell Lymphoma): diffuse large B cell lymphoma;
FISH (fluorescence in situ hybridization): the fluorescent in-situ hybridization technique is an important nonradioactive in-situ hybridization technique, and is characterized in that a probe with fluorescent substances is jointed with target DNA by a special means according to the base complementary pairing principle, and finally, the position of the target DNA can be directly observed by using a fluorescent microscope.
Diffuse large B-cell lymphoma is the most common subtype of non-hodgkin lymphoma, with high clinical and biological heterogeneity. With the continuous development of genome and transcriptome analysis technology, personalized treatment is gradually realized, and DLBCL typing has important significance. Currently, DLBCL can be divided into generation center B cell-like (GCB) and activated B cell-like (ABC) subtypes based on gene expression profiles; DNA mutation based tumor genes and molecular typing methods of the mutated genes, etc. However, in the prior art, no prognosis stratification factors such as DLBCL typing are satisfactory, and the optimal classification method is not yet known, and the value of the classification methods in terms of prognosis and treatment is still unclear.
Therefore, the invention aims to carry out molecular typing on DLBCL patients, researches show that MYC/BCL2 protein expression level and immune microenvironment cooperate to have unique effect on prognosis of various DLBCL subtype patients, is beneficial to prognosis judgment of the patients, can adjust treatment strategies of high-risk group patients in a targeted manner, and has important theoretical significance and clinical value on accurate treatment of the DLBCL.
The invention relates to a diffuse large B-cell lymphoma prognosis model based on MYC/BCL2 double expression and immune microenvironment, which is used for evaluating prognosis risks of patients with different diffuse large B-cell lymphoma subtypes based on protein expression levels of MYC and BCL2 and tumor immune cell infiltration degree.
Wherein the degree of tumor immune cell infiltration comprises the degree of infiltration by NK cells, T cells and macrophages and the patients with diffuse large B-cell lymphoma subtype comprise EZB subtype, MCD subtype, ST2 subtype, BN2 subtype and LymphGen unclassified subtype.
Specifically, the prognostic indicators of the prognostic model for the EZB subtype, wherein the protein expression levels of MYC and BCL2 are more than or equal to 70% as prognostic bad factors; the infiltration degree CD56+ NK cells > 3% of NK cells is a favorable factor for prognosis;
the prognosis index of the prognosis model to MCD subtype, the infiltration degree CD8+ T cells of T cells is more than or equal to 5% as a prognosis favorable factor;
for the prognosis indexes of the ST2 subtype of the prognosis model, the infiltration degree T cells of T cells is more than or equal to 24.5%, the infiltration degree Macrophages of Macrophages is more than or equal to 8.8%, and the infiltration degree NK cells of NK cells is more than or equal to 2.9% are poor prognosis factors;
for the prognosis indexes of the prognosis model for the BN2 subtype, protein expression levels of MYC and BCL2 are more than or equal to 70% and are poor prognosis factors, and infiltration degrees of T cells, namely CD4+ T cells, are more than or equal to 12.9% and are favorable prognosis factors;
the prognostic index of the prognostic model to the unclassified subtype of LymphGen is characterized in that the protein expression level of MYC and BCL2 is more than or equal to 70%, the infiltration degree CD56+ NK cells of NK cells is more than or equal to 12.3% and is a prognostic favorable factor, the infiltration degree CD8+ T of T cells is more than or equal to 17.4%, and the infiltration degree Macrophages of Macrophages is less than or equal to 20% and is a prognostic unfavorable factor.
The invention also provides a method for establishing the prognosis model, wherein each prognosis index is established by the following method:
s100: acquiring sample data of a patient with diffuse large B cell lymphoma receiving standard immunochemistry, and performing gene deep sequencing and FISH analysis on tumor-related genes to obtain a gene deep sequencing result and a FISH analysis result;
s200: classifying patients with diffuse large B-cell lymphoma subtype into EZB subtype, MCD subtype, ST2 subtype, BN2 subtype and LymphGen unclassified subtype by adopting a LymphGen typing system;
s300: based on different diffuse large B cell lymphoma subtypes, carrying out relationship risk aiming at the protein expression levels of MYC and BCL2 and prognosis to obtain prognostic indicators of the protein expression levels of MYC and BCL2 in different subtypes;
s400: protein expression of related biomarkers is analyzed through multicolor immunofluorescence histochemistry, diffuse large B cell lymphoma patient samples of different genetic subtypes are compared, and the comparison result obtains that immunity microenvironments of a BN2 subtype and a LymphGen unclassified subtype are more active than those of an MCD subtype, an EZB subtype and an ST2 subtype;
s500: and (3) carrying out relation analysis on T cells, macrophages and NK cells and prognosis to obtain a prognostic index of the tumor immune cell infiltration degree.
Specifically, the establishment method comprises deep sequencing of 275 lymphoma related genes, FISH detection (detecting BCL2/BCL6 gene rearrangement and TP53 deletion), immunohistochemical detection (detecting MYC/BCL2 protein expression level), and fluorescent multiple immunohistochemical detection of 13 immune cell markers (detecting infiltration levels of T cells, B cells, NK cells and macrophages). The following supplementary description is made for each step of the above-mentioned establishment method:
(1) genetic subtype classification of DLBCL based on genomic sequencing and gene rearrangement data:
step 1: the invention carries out gene deep sequencing and FISH analysis (including BCL2/BCL6 gene rearrangement and TP53 deletion) on the basis of 275 lymphoma related genes in 424 DLBCL patient samples receiving standard immunochemotherapy, and deeply analyzes the gene deep sequencing result and the FISH analysis result.
Step 2: the present invention employs the LymphGen typing system for 128 (30%) DLBCL patient cases. Is further subdivided into EZB (n-73), MCD (n-25), ST2 (n-14), BN2 (n-12) or a53 (n-4) subtypes, while another 296 cases are classified as unclassified subtypes, locating the LymphGen unclassified subtype. In accordance with the results of other related studies, MCD, BN2 and A53 gene subtypes belong mainly to ABC subtypes, while EZB and ST2 are mainly GCB subtypes.
Wherein, the gene deep sequencing and FISH detection results of patient samples are uploaded to a LymphGen typing system (https:// llmpp. nih. gov/LymphGen/index. php) for subtype classification of patients.
It is to be noted that the present inventors have found that gene subtypes do not show a significant effect on prognosis, but they show different gene expression profiles. According to the invention, DLBCL is subjected to molecular stratification through gene deep sequencing and FISH analysis results, and DLBCL patients are better classified and prognostically stratified, so that the method is of great importance for perfecting clinical parameters and biomarkers of characteristic classification and prognostic stratification of DLBCL patients.
(2) MYC/BCL2 protein expression levels can stratify EZB, BN2, and genetically unpatterned DLBCL:
and step 3: based on different diffuse large B cell lymphoma subtypes, carrying out relationship risk aiming at the protein expression levels of MYC and BCL2 and prognosis to obtain prognostic indicators of the protein expression levels of MYC and BCL2 in different subtypes;
further, the invention groups patient data samples according to MYC protein expression level ≥ 40%: 141 cases of MYC/BCL2 double expression group (73 cases of double high expression group and 68 cases of double expression but not high expression group according to the expression level of MYC protein is more than or equal to 70 percent) and 262 cases of non-MYC/BCL 2 double expression group. The results of the study found that the double high expression of MYC/BCL2 (DhE) had a significant adverse prognostic impact in the case of EZB subtype (fig. 1), BN2 subtype (fig. 2) and the unclassified subtype of LymphGen (fig. 3), but no prognostic impact in the case of MCD and ST2 subtypes.
These results indicate that for clinically poorly prognostic EZB subtypes, further stratification can be achieved by routine immunohistochemical testing of MYC/BCL 2.
(3) The prognostic significance of immune dysregulation and immune microenvironment biomarkers for different DLBCL gene subtypes vary:
and 4, step 4: protein expression of relevant biomarkers was analyzed by multicolor immunofluorescence histochemical analysis to compare diffuse large B-cell lymphoma patient samples of different genetic subtypes.
The tumor microenvironment where the tumor cells are located is composed of tumor cells, various interstitial cells (such as immune cells), extracellular matrix and the like. It is conventionally considered in the art that DLBCL is seen in tumor tissues as diffuse lymphoma cell infiltration, and normal immune cell components are few, and the DLBCL belongs to immune cold tumor.
However, the applicant researches and discovers that the compound plays a crucial role in regulating the onset, the progression and the metastasis of tumors and has a profound influence on the treatment effect. The interaction of DLBCL tumor cells with various immune cells is crucial for the development of the disease, which also increases the complexity of the DLBCL subtype. In order to discuss the prognostic significance of immune disorder and immune microenvironment biomarkers in different DLBCL genetic subtypes, the invention analyzes the protein expression of the immune biomarkers through multicolor immunofluorescence organization and compares DLBCL samples of different genetic subtypes.
And 5: and (3) carrying out relation analysis on T cells, macrophages and NK cells and prognosis to obtain a prognostic index of the tumor immune cell infiltration degree. The research result of the applicant finds that: the BN2 subtype and the LymphGen unclassified subtype are more active than the immune microenvironment of the a53 subtype, MCD subtype, EZB subtype and ST2 subtype.
Further analysis on the relationship between T cells, macrophages and NK cells and prognosis shows that:
results 1: the degree of NK cell infiltration (fig. 4) and T cell infiltration (fig. 5) were prognostic favouring factors in the EZB and MCD subtypes, respectively.
Results 2: in the ST2 subtype samples, the degree of T cell, macrophage and NK cell infiltration were all prognostic adverse factors (fig. 6).
Results 3: in the BN2 subtype, T cell infiltration was a prognostic favourite factor (figure 7).
Results 4: in the non-classified subset of LymphGen, NK cell infiltration showed a favorable prognostic effect, while T cell and macrophage infiltration showed an unfavorable prognostic effect (fig. 8).
These findings indicate that the prognostic significance of immune biomarkers is influenced by the genetic background.
Based on the above comprehensive analysis results, MYC/BCL2 dual high expression, gene subtype and tumor microenvironment have unique roles in DLBCL prognosis, and accurate medical treatment of DCBCL requires complete molecular assessment and more accurate genetic subtype classification.
The invention also provides the application of a diffuse large B-cell lymphoma prognosis model based on MYC/BCL2 dual expression and immune microenvironment, which is used for evaluating the prognosis risk of patients with diffuse large B-cell lymphoma of EZB subtype, MCD subtype, ST2 subtype, BN2 subtype and LymphGen unclassified subtype.
The invention also provides a diffuse large B cell lymphoma prognosis method of the diffuse large B cell lymphoma prognosis model based on MYC/BCL2 dual expression and immune microenvironment, which comprises the following steps:
s1000: tumor tissues of patients with diffuse large B cell lymphoma are obtained, gene deep sequencing and FISH detection of lymphoma related genes are carried out, and the subtype of the patients with diffuse large B cell lymphoma is determined.
In the implementation, the invention innovatively carries out gene deep sequencing and FISH detection on a patient sample, uploads the gene deep sequencing and FISH detection results of the patient sample to a LymphGen typing system (https:// llmpp.
In one embodiment, the classification includes an EZB subtype, an MCD subtype, an ST2 subtype, a BN2 subtype, and a LymphGen unclassified subtype.
S2000: immunohistochemical detection of tumor tissues, fluorescence multiplex immunohistochemical detection of 13 immunocyte markers, detection of protein expression levels of MYC and BCL2, and degree of tumor immunocyte infiltration were performed.
S3000: the patient prognostic risk is assessed based on a prognostic model that assesses prognostic risk in patients with different diffuse large B-cell lymphoma subtypes based on protein expression levels of MYC and BCL2 and the degree of tumor immune cell infiltration.
Prognostic model verification
Tumor tissues of DLBCL patients at the initial diagnosis are collected and subjected to deep sequencing of 275 lymphoma-associated genes, FISH detection (detecting BCL2/BCL6 gene rearrangement and TP53 deletion), immunohistochemical detection (detecting MYC/BCL2 protein expression level), and fluorescent multiplex immunohistochemical detection of 13 immune cell markers (detecting infiltration levels of T cells, B cells, NK cells and macrophages).
Uploading LymphGen typing system (https:// llmpp. nih. gov/LymphGen/index. php) to classify the subtype of the patient based on gene deep sequencing and FISH detection results;
follow-up was performed during the treatment of the patients. Until the follow-up deadline no death occurred, the last follow-up date was used as the cutoff value for analysis. The death date is obtained from clinical history, from a death registry or by phone call to patient relatives follow-up. OS is calculated in months and is defined as the time from the time of the disease diagnosis to the time of death or last follow-up due to any cause.
Male patients, 69 years old, classified as EZB subtype based on the LymphGen typing system, assessed prognosis based on MYC/BCL2 protein expression level, immune cell infiltration level:
wherein, MYC/BCL2 is highly expressed (gene protein expression is more than or equal to 70 percent), and NK cell infiltration is 2.6 percent (NK cells is less than 3 percent). The evaluation result indicates that the patient is of a poor prognosis type. The results show that: by the follow-up date, the patients have died, with an overall survival of 6 months, well below the median survival of DLBCL patients, with a poor prognosis.
② female patients, age 45, classified as a LymphGen unclassified subtype based on the LymphGen typing system; based on MYC/BCL2 protein expression level, immune cell infiltration level, prognosis was evaluated:
wherein, MYC/BCL2 double high expression (gene protein expression is more than or equal to 70%); and 8.6% of NK cell infiltration (NK cells < 12.3%), 22.4% of T cell infiltration degree CD8+ T (T cells > 17.4%), 10.9% of macrophage infiltration degree Macrophages (Macrophages < 20%) are prognosis adverse factor evaluation results, and the patient is indicated as a poor prognosis type. The results show that: by the follow-up date, the patients have died, with an overall survival of 7.8 months, well below the median survival of DLBCL patients, with a poor prognosis.
③ female patient, age 67, classified as MCD subtype based on the LymphGen typing system, assessment of prognosis based on MYC/BCL2 protein expression level, immune cell infiltration level:
wherein, MYC/BCL2 double high expression (gene protein expression is more than or equal to 70%); and the degree of infiltration of T cells, CD8+ T4.5% (Tcells > 5%) was the prognostic adverse factor assessment, indicating that the patient was of a poor prognosis type. The results show that: by the follow-up date, the patients had died, with an overall survival of 6 months, which was lower than the median survival of DLBCL patients, with a poorer prognosis.
Female patient, age 35, classified as ST2 subtype based on the LymphGen typing system; determining the subtype of the patient and evaluating the prognosis based on the expression level of MYC/BCL2 protein, the level of infiltration of immune cells:
wherein, the infiltration degree of NK cells is 3.6% (NK cells > 2.9%), the infiltration degree of T cells is CD8+ T is 29% (Tcells > 24.5%), the infiltration degree of Macrophages is 11.3% (Macrophages > 8.8%) is the prognosis adverse factor evaluation result, which indicates that the patient is of poor prognosis type. The results show that: by the follow-up date, the patients had died, with an overall survival of 9.2 months, below the median survival of DLBCL patients, with a poorer prognosis.
Through clinical verification, the gene subtype, MYC/BCL2 protein expression level and immune microenvironment synergistically play a unique role in prognosis of various DLBCL subtype patients, so that the method is not only beneficial to prognosis judgment of the patients, but also beneficial to pertinently adjusting treatment strategies of high-risk group patients, and has important theoretical significance and clinical value for accurate treatment of DLBCL.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention in any way, so that any modification, equivalent change and modification made to the above embodiment according to the technical spirit of the present invention are within the scope of the technical solution of the present invention.
Claims (8)
1. The diffuse large B-cell lymphoma prognosis model based on MYC/BCL2 dual expression and immune microenvironment is characterized in that the prognosis model is used for evaluating the prognosis risk of patients with different diffuse large B-cell lymphoma subtypes based on the protein expression level and the tumor immune cell infiltration degree of MYC and BCL 2.
2. The diffuse large B-cell lymphoma prognosis model based on MYC/BCL2 dual expression and immune microenvironment of claim 1, wherein:
the degree of tumor immune cell infiltration includes the degree of infiltration of NK cells, T cells and macrophages.
3. The diffuse large B-cell lymphoma prognosis model based on MYC/BCL2 dual expression and immune microenvironment of claim 2, said diffuse large B-cell lymphoma subtype patients comprising EZB subtype, MCD subtype, ST2 subtype, BN2 subtype, and LymphGen unclassified subtype.
4. The diffuse large B-cell lymphoma prognosis model based on MYC/BCL2 dual expression and immune microenvironment of claim 3, wherein:
the prognostic indicators of the prognostic model to the EZB subtype, wherein the protein expression levels of MYC and BCL2 are more than or equal to 70 percent as poor prognostic factors; the infiltration degree CD56+ NK cells > 3% of NK cells is a favorable factor for prognosis;
the prognosis index of the prognosis model to MCD subtype, the infiltration degree CD8+ T cells of T cells is more than or equal to 5% as a prognosis favorable factor;
for the prognosis indexes of the ST2 subtype of the prognosis model, the infiltration degree T cells of T cells is more than or equal to 24.5%, the infiltration degree Macrophages of Macrophages is more than or equal to 8.8%, and the infiltration degree NK cells of NK cells is more than or equal to 2.9% are poor prognosis factors;
for the prognosis indexes of the prognosis model for the BN2 subtype, protein expression levels of MYC and BCL2 are more than or equal to 70% and are poor prognosis factors, and infiltration degrees of T cells, namely CD4+ T cells, are more than or equal to 12.9% and are favorable prognosis factors;
the prognostic index of the prognostic model to the unclassified subtype of LymphGen is characterized in that the protein expression level of MYC and BCL2 is more than or equal to 70%, the infiltration degree CD56+ NK cells of NK cells is more than or equal to 12.3% and is a prognostic favorable factor, the infiltration degree CD8+ T of T cells is more than or equal to 17.4%, and the infiltration degree Macrophages of Macrophages is less than or equal to 20% and is a prognostic unfavorable factor.
5. The MYC/BCL2 double expression and immune microenvironment-based diffuse large B-cell lymphoma prognosis model of claim 4, wherein the prognosis index of the prognosis model is established by the following method:
acquiring sample data of a patient with diffuse large B cell lymphoma receiving standard immunochemistry, and performing gene deep sequencing and FISH analysis on tumor-related genes to obtain a gene deep sequencing result and a FISH analysis result;
classifying patients with diffuse large B-cell lymphoma subtype into EZB subtype, MCD subtype, ST2 subtype, BN2 subtype and LymphGen unclassified subtype by adopting a LymphGen typing system;
based on different diffuse large B cell lymphoma subtypes, carrying out relationship risk aiming at the protein expression levels of MYC and BCL2 and prognosis to obtain prognostic indicators of the protein expression levels of MYC and BCL2 in different subtypes;
protein expression of related biomarkers is analyzed through multicolor immunofluorescence histochemistry, diffuse large B cell lymphoma patient samples of different genetic subtypes are compared, and the comparison result obtains that immunity microenvironments of a BN2 subtype and a LymphGen unclassified subtype are more active than those of an MCD subtype, an EZB subtype and an ST2 subtype;
and (3) carrying out relation analysis on T cells, macrophages and NK cells and prognosis to obtain a prognostic index of the tumor immune cell infiltration degree.
6. Use of a prognostic model for diffuse large B-cell lymphoma based on MYC/BCL2 dual expression and immune microenvironment, characterized in that the prognostic model is used to assess the prognostic risk in patients with diffuse large B-cell lymphoma of EZB subtype, MCD subtype, ST2 subtype, BN2 subtype and the unsorted subtype of LymphGen.
7. The diffuse large B cell lymphoma prognosis method based on MYC/BCL2 dual expression and immune microenvironment is characterized by comprising the following steps:
obtaining tumor tissues of a patient with diffuse large B cell lymphoma, performing gene deep sequencing and FISH (fluorescence in situ hybridization) detection on lymphoma related genes, and determining the subtype of the patient with diffuse large B cell lymphoma;
performing immunohistochemical detection on the tumor tissue, performing fluorescence multiplex immunohistochemical detection on immune cell markers, and detecting protein expression levels of MYC and BCL2 and tumor immune cell infiltration degree;
the patient prognostic risk is assessed based on a prognostic model that assesses prognostic risk in patients with different diffuse large B-cell lymphoma subtypes based on protein expression levels of MYC and BCL2 and the degree of tumor immune cell infiltration.
8. The diffuse large B-cell lymphoma prognosis method according to claim 7, based on MYC/BCL2 dual expression and immune microenvironment, characterized by:
the prognostic indicators of the prognostic model to the EZB subtype, wherein the protein expression levels of MYC and BCL2 are more than or equal to 70 percent as poor prognostic factors; the infiltration degree CD56+ NK cells > 3% of NK cells is a favorable factor for prognosis;
the prognosis index of the prognosis model to MCD subtype, the infiltration degree CD8+ T cells of T cells is more than or equal to 5% as a prognosis favorable factor;
for the prognosis indexes of the ST2 subtype of the prognosis model, the infiltration degree T cells of T cells is more than or equal to 24.5%, the infiltration degree Macrophages of Macrophages is more than or equal to 8.8%, and the infiltration degree NK cells of NK cells is more than or equal to 2.9% are poor prognosis factors;
for the prognosis indexes of the prognosis model for the BN2 subtype, protein expression levels of MYC and BCL2 are more than or equal to 70% and are poor prognosis factors, and infiltration degrees of T cells, namely CD4+ T cells, are more than or equal to 12.9% and are favorable prognosis factors;
the prognostic index of the prognostic model to the unclassified subtype of LymphGen is characterized in that the protein expression level of MYC and BCL2 is more than or equal to 70%, the infiltration degree CD56+ NK cells of NK cells is more than or equal to 12.3% and is a prognostic favorable factor, the infiltration degree CD8+ T of T cells is more than or equal to 17.4%, and the infiltration degree Macrophages of Macrophages is less than or equal to 20% and is a prognostic unfavorable factor.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101470112A (en) * | 2007-12-28 | 2009-07-01 | 上海交通大学医学院附属瑞金医院 | Molecule mark for diffuse large b-cell lymphoma treating guide and prognosis judgment |
| WO2009082856A1 (en) * | 2007-12-28 | 2009-07-09 | Ruijin Hospital Affiliated To The Shanghai Jiao Tong University Medical School | Molecule marker used for prognosticating diffuse large b cell lymphoma |
-
2021
- 2021-11-12 CN CN202111335942.1A patent/CN114085910A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101470112A (en) * | 2007-12-28 | 2009-07-01 | 上海交通大学医学院附属瑞金医院 | Molecule mark for diffuse large b-cell lymphoma treating guide and prognosis judgment |
| WO2009082856A1 (en) * | 2007-12-28 | 2009-07-09 | Ruijin Hospital Affiliated To The Shanghai Jiao Tong University Medical School | Molecule marker used for prognosticating diffuse large b cell lymphoma |
Non-Patent Citations (2)
| Title |
|---|
| LEO MERIRANTA等: "Molecular background delineates outcome of double protein expressor diffuse large B-cell lymphoma", BLOOD ADVANCES, vol. 4, no. 15, 11 August 2020 (2020-08-11), pages 3742 - 3753 * |
| 黄玉洁等: "基于肿瘤免疫微环境的弥漫大B 细胞淋巴瘤预后分析", 肿瘤预防与治疗, vol. 34, no. 2, 28 February 2021 (2021-02-28), pages 108 - 116 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117153252A (en) * | 2023-08-31 | 2023-12-01 | 山东第一医科大学附属省立医院(山东省立医院) | Prognosis biomarker for patients with diffuse large B cell lymphoma, and system and application thereof |
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