Prognostic Analysis Of Clinical Features And Gene Mutation Of Primary Breast Lymphoma

Objective:Lymphoma is an immune system malignant tumor with great heterogeneity,which was divided into two categories:Hodgkin lymphoma?HL?and Non-Hodgkin lymphoma?NHL?.A subset of NHL that is thought to originate outside the lymph nodes or spleen was called primary extranodal Non-Hodgkin lymphoma?PE-NHL?.Despite the relatively high incidence of pe-nhl,primary breast lymphoma?PBL?was rare,with rapid clinical progression,poor prognosis and a high risk of central nervous system recurrence.At present,there is no definite treatment plan for PBL.In order to better guide the establishment of ideal treatment plan and improve the cure rate of this invasive disease,we performed second-generation gene sequencing on the pathological tissues of 16 patients to analyze the relationship between the gene mutation spectrum of PBL and the clinical characteristics and disease prognosis,so as to provide a basis for the clinical diagnosis and targeted therapy of PBL.The most common form of pe-nhl is gastric lymphoma,followed by vessel-ring lymphoma.Other sites include bone,skin,brain,ectoderm,thyroid and testes.Less common sites are breast,lung and bladder.Despite the relatively high incidence of pe-nhl,primary breast lymphoma?PBL?was rare,accounting for 1.7%to 2.2%of extra-lymphadenomas and 0.38%to 0.7%of all Non-Hodgkin lymphomas^[1-6].Through extensive literature review,we found that the Nuclear Factor Kappa-B?NF-?B?signaling pathway plays a crucial role in lymphohematopoietic tumors.NF-?B mediates tumor formation by transcriptional regulation of cell proliferation,angiogenesis,and inhibition of apoptotic genes.Cell tolerance was controlled by stimulating certain genes that inhibit apoptosis in cancer cells and normal cells.Therefore,a better understanding of NF-?B signal and its regulatory factors is essential for the development of targeted therapy.Methods:1. To collect 16 patients with PBL were diagnosed by The Fourth Hospital of Hebei Medical University from June 2009 to October 2019,with pathological diagnosis and complete clinical data.With the application of second-generation sequencing technology,targeted large-scale gene sequencing was performed on the pathological samples of patients to comprehensively analyze the gene expression of PBL and its relationship with disease prognosis.2. The relationship between clinical features and prognosis of patients with primary breast lymphoma was retrospectively analyzed.3.Statistical software SPSS21.0 was used for statistical analysis.Results:1.16 patients'samples were analyzed by second-generation sequencing,and the mutation status was as follows:among the 112 anti-mutant genes,the ones with high mutation frequency were PIM1,MYD88,DTX1,CD79B,KMT2D,TNFAIP3 and ITPKB.The mutation rate of PIM1 gene was 68.75%?11 cases?,the mutation rate of MYD88 gene was 56.25%?9 cases?,and the mutation rate of DTX1,CD79B and KMT2D genes was 31.25%?5 cases?.2. PIM1 gene mutation was correlated with age and pathological type of PBL patients?P=0.015,P=0.024?,and was not significantly correlated with other clinical characteristics?including primary site,Ann Arbor staging,IPI score,lactate dehydrogenase,bone marrow infiltration,B symptoms,ki-67,and beta-2 microglobulin??P>0.05?.TNFAIP3 gene mutation was correlated with the pathological type of PBL patients?P=0.006?,but not with other clinical characteristics.KMT2D gene mutation was correlated with the primary site?P=0.038?,but not with other clinical characteristics.Other high-frequency mutated genes MYD88,DTX1,CD79B and ITPKB had no significant correlation with all the above clinical characteristics?P>0.05?.3. Kathrin-meier survival curve analysis was used to analyze patients'OS and PFS.PIM1,MYD88,CD79B,TNFAIP3,KMT2D,ITPKB and DTX1genes mutated had no significant correlation with the prognosis?P>0.05?,however,there is a tendency to shorten OS and PFS,which may lead to poor prognosis.4. Kaplan-meier survival curve analysis was used to analyze patients'OS and PFS.The age of 60 or more,clinical stage?,IPI score 3 to 5 points,LDH increased,and beta-2 microglobulin increased had no significant correlation with the prognosis?P>0.05?,and there was no statistically significant difference,but there was a tendency to shorten OS and PFS,which may lead to poor prognosis.5. Kaplan-meier survival curve analysis was used to analyze the OS and PFS of the patients.Compared with the single chemotherapy group,the combined chemoradiotherapy group had better OS?P<0.05?.Whether rituximab was used,rituximab combined with CHOP or CHOP-like immunochemotherapy was used,and whether intrasheath injection was used to prevent central infiltration had no significant difference with the prognosis?P>0.05?.Conclusions:1.PIM1,MYD88,DTX1,CD79B,KMT2D,TNFAIP3 and ITPKB are genes with high frequency mutations in PBL.The mutation rate of PIM1 gene was 68.75%?11 cases?,the mutation rate of MYD88 gene was 56.25%?9cases?,and the mutation rate of DTX1,CD79B and KMT2D genes was31.25%?5 cases?,the mutation rate of TNFAIP3 and ITPKB gene was 25%?4cases?,2.Mutations in PIM1,MYD88,DTX1,CD79B,KMT2D,TNFAIP3,and ITPKB genes have been detected in PBL with a tendency to shorten OS and PFS,which may lead to poor prognosis.3.The age of 60 or more,clinical stage?,IPI score 3 to 5 points,LDH increased,and beta-2 microglobulin increased have a tendency to shorten OS and PFS,which may lead to poor prognosis.4.Chemotherapy combined with radiotherapy had a positive effect on the survival prognosis of PBL.