| BackgroundAccording to the 2020 global cancer data released by the International Agency for Research on Cancer(IARC)of the World Health Organization,breast cancer is the most common malignant tumor in women,and its new number reached 2.3 million.Breast cancer is now the most common cancer among Chinese women and the sixth leading cause of death related to cancer.The current breast cancer treatment is based on surgical treatment,supplemented by comprehensive treatments such as radiotherapy,chemotherapy,endocrine therapy,and targeted therapy.The expression of programmed cell death factor 4(PDCD4)is often down-regulated in a variety of cancers including breast,colon,liver,lung,pancreatic and skin cancers.PDCD4 overexpression inhibits cell proliferation,while knocking out the PDCD4 gene promotes cell proliferation.The inhibitory effect of PDCD4 on tumorigenesis is believed to be achieved by inhibiting the translation of a series of genes related to tumor cell proliferation,migration,invasion and metastasis.Stress-activated protein kinase interacting protein 1(SIN1)is an important part of mTORC2 and a key regulator of the AKT pathway.PDCD4 has the characteristics of regulating AKT activity.Tissue microarray technology(TMA)refers to a technique in which partial tumor locations are selected from a complete paraffin specimen(donor wax block),and multiple samples are arranged in a certain order on the acceptor wax block for sectioning and analysis.This technology has an unprecedented degree of standardization.There is no research to prove whether PDCD4 and SIN1 are related in breast cancer,and whether they play a role in the pathological characteristics and clinical prognosis of breast cancer patients in the same pathway.ObjectiveTo study the relationship between PDCD4 and SIN1 and clinicopathological parameters of breast cancer and their influence on survival and prognosis.This study hopes to find new targets for the treatment of breast cancer and provide new directions for the prognosis of breast cancer.Materials and methodsThis study selected a total of 327 breast cancer patients in the same treatment group who underwent surgical treatment at the Breast Surgery Department of Shandong University Qilu Hospital from December 2008 to September 2012.All cases adopted modified radical mastectomy or radical mastectomy.Collect clinical data and pathological results of patients included in the study.Tumor tissue specimens were taken from patients during surgery.All cases included in the study were followed up by telephone,and the deadline for follow-up was January 2021.All paraffin tissues were prepared into tissue microarrays and then sliced.After the slices,PDCD4 antibody and SIN1 antibody were used for immunohistochemical staining.According to the staining intensity and the positive rate of stained cells,the protein expression is judged as positive or negative.Statistics include tissue types,molecular subtypes,histological grades,T staging,pN staging,pTNM staging,Ki-67 positive rate and other clinicopathological data.The relationship between clinicopathological parameters and the expression of PDCD4 protein and SIN1 protein was tested by Pearson χ2.Whether the expression of PDCD4 protein and SIN1 protein was correlated was analyzed by Spearman rank correlation.Kaplan-Meier method was used to analyze the connection between age,tissue type,molecular subtype,histological grade,Ki-67 positive rate,T stage,pN stage,pTNM stage,PDCD4 and SIN1 protein expression,and univariate analysis of overall survival was performed.It was considered statistically significant when P<0.05.Results1.Among the 327 breast cancer patients,183 were younger than 50 years old,and 144 were older than or equal to 50 years old.The relationship between PDCD4 and SIN1 and age was not statistically significant(P=0.751,P=0.903);there was no statistically significant difference in the expression of PDCD4 and SIN1 between age groups(P=0.450).2.There were 259 cases of invasive carcinoma,38 cases of invasive carcinoma combined with carcinoma in situ,and 30 cases of carcinoma in situ.The PDCD4 deletion rate of invasive carcinoma was greater than that of carcinoma in situ,and the difference was statistically significant(P=0.022),and the difference between the other groups was not statistically significant(P>0.05).There was no difference between the positive rate of SIN1 expression and the histological type of breast cancer(P>0.05);the proportion of PDCD4(-)SIN1(+)in invasive carcinoma is higher than that of carcinoma in situ,the difference is statistically significant(P=0.027),and the other histological types have no difference in the expression of PDCD4 and SIN1(P=0.450).3.There were 80 cases of Luminal A breast cancer,119 cases of Luminal B breast cancer,61 cases of Her-2 positive breast cancer,and 67 cases of triple negative breast cancer.The PDCD4 deletion rate increased in Luminal A,Luminal B,triple-negative and Her-2 positive breast cancers in turn,and the difference was statistically significant(P=0.000);The positive rate of SIN1 increased in Luminal A,Luminal B,triple-negative and Her-2 positive breast cancers,and the difference was statistically significant(P=0.005).The ratio of PDCD4(-)SIN1(+)in Luminal A,Luminal B,triple-negative and Her-2 positive breast cancers was increased sequentially,and the difference was statistically significant(P=0.000).4.There were a total of 264 cases of breast invasive ductal carcinoma.The histological classification was 11 cases of grade I,184 cases of grade II,and 69 cases of grade ⅢI.The PDCD4 deletion rate in grade I,grade II,and grade Ⅲ breast cancers increased in turn,and the difference was statistically significant(P=0.000);the positive rate of SIN1 increased in grade I,grade Ⅱ,and grade Ⅲ breast cancer,and the difference was statistically significant(P=0.011);the proportion of PDCD4(-)SIN1(+)in grade Ⅰ,grade II,and grade Ⅲ breast cancer increased sequentially,and the difference was statistically significant(P=0.009).5.There were 30 cases of carcinoma in situ(Tis),291 cases were T1 or T2,and 6 cases were T3.The PDCD4 deletion rate of T1/T2 breast cancer is higher than that of carcinoma in situ,the difference is statistically significant(P=0.026),the difference between the other groups is not statistically significant(P>0.05),the positive rate of SIN1 expression and T stage are not statistically significant(P>0.05).The ratio of PDCD4(-)SIN1(+)in breast cancer in T1/T2 stage is higher than that in carcinoma in situ(P=0.035).The other T stages has no statistically significant difference in the expression of PDCD4 and SIN1(P=0.059).6.Pathological lymph node staging was N0/N1 stage in 271 cases,and pathological lymph node staging was N2/N3 stage in 56 cases.There was no significant difference between PDCD4,SIN1 and pN staging(P=0.602,P=0.751);pN staging had no significant difference in the expression of PDCD4 and SIN1(P=0.661).7.The pathological TNM staging was 30 cases of stage 0,238 cases of stage Ⅰ and II,and 59 cases of stage Ⅲ.The PDCD4 deletion rate of stage Ⅰ/Ⅱ breast cancer was higher than that of carcinoma in situ,and the difference was statistically significant(P=0.020).The difference between the other groups was not statistically significant(P>0.05).The positive rate of SIN1 expression and pTNM staging were not statistically significant(P>0.05).The ratio of PDCD4(-)SIN1(+)in stage Ⅰ/Ⅱ breast cancer is higher than that of carcinoma in situ,and the proportion of PDCD4(-)SIN1(+)in stageⅢ breast cancer is higher than that of carcinoma in situ,the difference is statistically significant(P=0.036,P=0.039),and the difference between PDCD4 and SIN1 in other pTNM stages was not statistically significant(P=0.086).8.There were 94 cases of Ki-67%<14%cases of breast cancer,and 228 cases of breast cancer with Ki-67%)14%.The breast cancer with Ki-67%]14%had a higher rate of PDCD4 deletion,high positive rate of SIN1,the difference is statistically significant(P=0.007,P=0.003);Ki-67%)14%group PDCD4(-)SIN1(+)ratio was higher than the Ki-67%<14%group,and the difference was statistically significant(P=0.001).9.The median follow-up time of 327 breast cancer patients was 118 months,35 deaths were followed up,and the overall survival rate was 89.3%.Among them,the N stage is high,the TNM stage is high,and the positive expression of SIN1 indicates a worse overall survival rate(P=0.000,P=0.000,P=0.043);the remaining age,histological type,molecular subtype,histological grade,T stage,Ki-67 expression and PDCD4 expression have nothing to do with the overall survival rate of patients(P>0.05)10.Among 327 breast cancer patients,123 cases(37.6%)were positive for PDCD4 and SIN1,28 cases(8.6%)were negative for PDCD4 and SIN1,and 87(26.6%)cases were negative for PDCD4 and positive for SIN 1,89 cases(27.2%)had positive PDCD4 expression and negative SIN1 expression.The expression of PDCD4 was negatively correlated with the expression of SIN1(r=-0.176,P=0.001).Conclusions1.PDCD4 in breast cancer expression is missing,the higher the degree of malignancy,the more active proliferation,the higher the rate of deletion;SIN1 in breast cancer expression increased,the higher the degree of malignancy,the more active proliferation,the higher the expression rate.2.There is a weak negative correlation between the expression of PDCD4 and SIN1 in breast cancer.3.Breast cancer patients with positive SIN1 expression,high N stage,and high TNM stage have worse prognosis.4.SIN1 can be an important factor in assessing prognosis in breast cancer patients. |
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