NINJ1 Facilitates Abdominal Aortic Aneurysm Formation via Blocking TLR4-ANXA2 Interaction and Enhancing Macrophage Infiltration.

Abdominal aortic aneurysm (AAA) is a common and potentially life-threatening condition. Chronic aortic inflammation is closely associated with the pathogenesis of AAA. Nerve injury-induced protein 1 (NINJ1) is increasingly acknowledged as a significant regulator of the inflammatory process. However, the precise involvement of NINJ1 in AAA formation remains largely unexplored. The present study finds that the expression level of NINJ1 is elevated, along with the specific expression level in macrophages within human and angiotensin II (Ang II)-induced murine AAA lesions. Furthermore, Ninj1flox/flox and Ninj1flox/floxLyz2-Cre mice on an ApoE-/- background are generated, and macrophage NINJ1 deficiency inhibits AAA formation and reduces macrophage infiltration in mice infused with Ang II. Consistently, in vitro suppressing the expression level of NINJ1 in macrophages significantly restricts macrophage adhesion and migration, while attenuating macrophage pro-inflammatory responses. Bulk RNA-sequencing and pathway analysis uncover that NINJ1 can modulate macrophage infiltration through the TLR4/NF-κB/CCR2 signaling pathway. Protein-protein interaction analysis indicates that NINJ1 can activate TLR4 by competitively binding with ANXA2, an inhibitory interacting protein of TLR4. These findings reveal that NINJ1 can modulate AAA formation by promoting macrophage infiltration and pro-inflammatory responses, highlighting the potential of NINJ1 as a therapeutic target for AAA.

[Analysis of multimodal ultrasound in differential diagnosis of salivary gland tumors].

PURPOSE: To explore the differential diagnosis of salivary gland tumors by multimodal ultrasound and to establish a preliminary scoring system by assigning meaningful parameters. METHODS: Seventy-seven tumors from 69 patients with salivary gland tumors were examined by two-dimensional gray-scale ultrasound, color Doppler flow imaging (CDFI), superb microvascular imaging(SMI), real time tissue elastography(RTE) and acoustic radiation force impulse (ARFI). Different scoring schemes were obtained for the assignment and combination of meaningful parameters. The ROC curve of each scheme was drawn, and the one with the largest area under the curve was taken as the best scoring scheme. SPSS 25.0 software package was used for statistical analysis of the data. RESULTS: There were significant differences in tumor shape, boundary, posterior echo, blood flow resistance index, RTE grade and ARFI average value between benign and malignant salivary gland tumors(P<0.05). The scoring scheme 7, which was composed of the above 6 parameters, was the best scoring scheme. When each parameter was assigned a score of 1, the total score was 6, and the area under the curve was 0.944. The sensitivity, specificity and accuracy of distinguishing benign and malignant salivary gland tumors with ≥4 points were 80.0%, 98.4% and 94.8%, respectively. CONCLUSIONS: Application of multimodal ultrasound and establishment of a scoring system can effectively improve the ability of ultrasound in the differential diagnosis of benign and malignant salivary gland tumors.

[Analysis of multimodal ultrasound in differential diagnosis of salivary gland tumors].

PURPOSE: To explore the differential diagnosis of salivary gland tumors by multimodal ultrasound and to establish a preliminary scoring system by assigning meaningful parameters. METHODS: Seventy-seven tumors from 69 patients with salivary gland tumors were examined by two-dimensional gray-scale ultrasound, color Doppler flow imaging (CDFI), superb microvascular imaging(SMI), real time tissue elastography(RTE) and acoustic radiation force impulse (ARFI). Different scoring schemes were obtained for the assignment and combination of meaningful parameters. The ROC curve of each scheme was drawn, and the one with the largest area under the curve was taken as the best scoring scheme. SPSS 25.0 software package was used for statistical analysis of the data. RESULTS: There were significant differences in tumor shape, boundary, posterior echo, blood flow resistance index, RTE grade and ARFI average value between benign and malignant salivary gland tumors(P<0.05). The scoring scheme 7, which was composed of the above 6 parameters, was the best scoring scheme. When each parameter was assigned a score of 1, the total score was 6, and the area under the curve was 0.944. The sensitivity, specificity and accuracy of distinguishing benign and malignant salivary gland tumors with ≥4 points were 80.0%, 98.4% and 94.8%, respectively. CONCLUSIONS: Application of multimodal ultrasound and establishment of a scoring system can effectively improve the ability of ultrasound in the differential diagnosis of benign and malignant salivary gland tumors.

Post-mastectomy immediate breast reconstruction is oncologically safe in well-selected T4 locally advanced breast cancer: a large population-based study and matched case-control analysis.

PURPOSE: Although it is well accepted that the survival outcome is most probably unaffected by immediate breast reconstruction (IBR) for T1-T3 tumors, the safety of IBR in T4 locally advanced breast cancer (LABC) remains unclear. METHODS: By using data from the Surveillance, Epidemiology, and End Results (SEER) database, the trend of IBR for female T4 LABC patients undergoing mastectomy, chemotherapy and radiotherapy was explored. The predictors of IBR in T4 LABC were evaluated by multivariate logistic regression. The survival outcomes were compared by means of Cox hazards models adjusting for known clinicopathological variables and stratifying on the T stage and contralateral prophylactic mastectomy (CPM). RESULTS: Altogether 714 cases underwent IBR between 1998 and 2015. The IBR cohort had a lower percentage of cases with T4d disease whereas higher percentage with CPM. The IBR rate was 10.1% and increased from 4.1% in 1998 to 17.7% in 2015. Since 2009, the rate of implant-based IBR exceeded that of the autologous tissue method. An age less than 45 years (OR 2.930, 95% CI 2.299-3.735) and CPM (OR 2.758, 95% CI 2.306-3.299) were the strongest predictors of IBR. In the 1:2 matched case-control analysis, IBR was not an independent prognostic factor for breast cancer specific-survival (BCSS) (HR 0.893, p = 0.236, 95% CI 0.741-1.077) and overall survival (OS) (HR 0.886, p = 0.183, 95% CI 0.741-1.059). BCSS and OS were similar among patients undergoing IBR whether they underwent CPM or not and whether they were inflammatory breast cancer (IBC) or not. CONCLUSIONS: IBR is oncologically safe in well-selected T4 LABC.

The Prognostic Significance of the Oncotype DX Recurrence Score in T1-2N1M0 Estrogen Receptor-Positive HER2-Negative Breast Cancer Based on the Prognostic Stage in the Updated AJCC 8th Edition.

BACKGROUND: This study aimed to evaluate the prognostic significance of the Oncotype DX recurrence score (RS) in T1-2N1M0 estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer based on the prognostic stage in the updated American Joint Commission on Cancer, 8th edition. METHODS: The Surveillance, Epidemiology, and End Results database was searched to identify ER-positive invasive ductal breast cancer in T1-2N1M0 with RS results diagnosed between 2004 and 2012. Patients with RS were categorized into low-risk (RS < 11), intermediate-risk (RS 11-25), and high-risk (RS > 25) groups. The distributions of clinical-pathological characteristics were compared among the RS risk groups using Pearson's Chi square. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared across RS groups using the log-rank statistic. Cox models were fitted to assess the factors independently associated with survival. RESULTS: The study enrolled 4059 cases categorized into prognostic stages IA to IIB. The RS risk groups were positively correlated with pathological prognostic stages (P < 0.001). The RS risk groups differed significantly in terms of BCSS and OS (P < 0.001). According to the multivariate analysis, RS risk group was an independent prognostic factor for BCSS and OS together with the pathological prognostic stage. The subgroup analysis showed similar survival rates across pathological prognostic stages in the RS low-risk group but significant differences in survival rates among pathological prognostic stages in the RS intermediate-risk group. The survival rates among the RS risk groups also differed significantly in pathological prognostic stage IA. CONCLUSIONS: Oncotype DX RS provided independent prognostic significance to complement the prognostic staging system.

Evaluation of the prognostic stage in the 8th edition of the American Joint Committee on Cancer in locally advanced breast cancer: An analysis based on SEER 18 database.

BACKGROUND: The new "prognostic stage" in the 8th edition of the American Joint Committee on Cancer (AJCC) incorporated important biologic factors such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), histologic grade and TNM stage into one system. The objective of this study was to evaluate the "prognostic stage" in locally advanced breast cancer (LABC) based on the Surveillance, Epidemiology, and End Results (SEER) 18 database. METHODS: 10053 LABCs diagnosed between 2010 and 2013 were enrolled. TNM stage was based on AJCC 7th edition. Comparisons of biologic factor proportions among stage changes were performed using Pearson's chi-square test. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier method and log rank testing with pairwise comparisons between different stages was conducted. Cox models were fitted to assess the independent prognostic factors. RESULTS: The prognostic stage grouped LABC into six stages: IB-IIIC among which IB-IIIA had a relatively better survival. It reassigned 74% LABCs to a different tumor stage. 60.4% cases in grade III and 68.3% cases with triple negative breast cancer were upstaged while 57.1% cases with ER/PR dual positivity were down staged. It was an independent prognostic factor of LABC. There were statistically significant survival differences among stage IB-IIIA, IIIB and IIIC. Among each TNM stage, there were statistically significant survival differences among stage changes. CONCLUSIONS: The prognostic stage provided accurate prognostic information for LABC compared with anatomic TNM stage. It will lead to accuracy in prognosis prediction and optimal treatment selection, and therefore, better outcomes.

Impact of central obesity on prognostic outcome of triple negative breast cancer in Chinese women.

PURPOSE: To evaluate the prognostic effect of central obesity on triple negative breast cancer (TNBC). METHODS: 206 TNBC patients treated from June 2006 to June 2015 were enrolled retrospectively. Body mass index (BMI) ≥25 kg/m(2) was the standard of obesity and waist circumference ≥80 cm was the standard of central obesity. Patient and tumor characteristics were compared between obesity categories. Survival differences between obesity categories were assessed with log-rank test in the univariate analysis and prognostic factors were then investigated by Cox regression analysis. RESULTS: 81 cases were with obesity (39.3 %). 71 cases were with central obesity (34.5 %). Patients with obesity or central obesity tended to be older (P = 0.022 for obesity; P = 0.013 for central obesity) and to have larger tumor size (P = 0.027 for obesity; P = 0.027 for central obesity). By Cox regression analysis, central obesity (DFS: HR 1.759; 95 % CI 1.009-3.065; P = 0.046. OS: HR 2.297; 95 % CI 1.184-4.456; P = 0.014) was identified as an independent prognostic factor. For central obesity with BMI ≥ 25 kg/m(2), the prognostic effect was more apparent (DFS: HR 1.845; 95 % CI 1.059-3.212; P = 0.031. OS: HR 2.377; 95 % CI 1.230-4.593; P = 0.010). CONCLUSION: Central obesity, especially with high BMI, was an independent prognostic factor for TNBC.

Prognostic effect analysis of molecular subtype on young breast cancer patients.

OBJECTIVE: To make a prognostic effect analysis of molecular subtype on young breast cancer patients. METHODS: Totally 187 cases of young breast cancer patients less than 40 years old treated in Obstetrics and Gynecology Hospital of Fudan University between June 2005 and June 2011 were included in our study. We described their clinical-pathological characteristics, disease-free survival (DFS) rate, and overall survival (OS) rate after a median follow-up period of 61 months. The factors associated with prognosis were also evaluated by univariate and multivariate analyses. RESULTS: All patients were premenopausal, with an average age of 35.36±3.88 years old. The mean tumor size was 2.43±1.53 cm. Eighty-one cases had lymph node metastasis (43.3%), 126 cases had lymphovascular invasion (67.4%), and 125 cases had histological grade III (66.8%) disease. Twenty-seven cases (14.4%) were Luminal A subtype, 99 cases (52.9%) were Luminal B subtype, 29 cases (15.5%) were human epidermal growth factor receptor 2 (HER-2) overexpression subtype, while 32 cases (17.1%) were triple negative breast cancer (TNBC) subtype according to 2013 St Gallen expert consensus. One hundred and thirty-five cases underwent mastectomy whereas 52 cases had breast-conserving surgery. One hundred and seventy-eight cases underwent adjuvant or neoadjuvant chemotherapy. Recurrence or metastasis occurred in 29 cases, 13 of which died. The 5-year DFS and OS rates were 84% and 92%. Multivariate analysis showed that nodal status (P=0.041) and molecular subtype (P=0.037) were both independent prognostic factors of DFS, while nodal status (P=0.037) and TNBC subtype (P=0.048) were both independent prognostic factors of OS. CONCLUSIONS: Molecular subtype is an independent prognostic factor of young breast cancer patients. TNBC has a high risk of relapse and death.

Comparison of invasive micropapillary and triple negative invasive ductal carcinoma of the breast.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast and triple negative breast cancer (TNBC) are both aggressive subtypes, but little information is available on their comparison. PATIENTS AND METHODS: Retrospective analysis of 95 IMPC and 200 TNBC-IDC (invasive ductal carcinoma) was conducted to compare the clinicopathologic characteristics and survivals. RESULTS: For IMPC, pN was the independent prognostic factor of local-regional recurrence free survival (LRRFS) (P = 0.045) and metastasis free survival (MFS) (P = 0.048), but not of overall survival (OS) (P = 0.165). For TNBC, pT and lymphovascular invasion (LVI) were both independent prognostic factors of MFS (pT: P = 0.006, LVI: P = 0.010) and OS (pT: P = 0.006, LVI: P = 0.001), but not for LRRFS (pT: P = 0.060, LVI: P = 0.503). IMPC exhibited more aggressive features than TNBC, including larger tumor size, a greater proportion of nodal involvement, and an increased incidence of LVI. After a median follow-up duration of 61 months, 5y-LRRFS rate was lower in IMPC than in TNBC, in entire cohort (71.4 ± 4.8% vs. 89.8 ± 2.2%, P < 0.001) and in node positive cases (64.2 ± 5.9% vs. 81.7 ± 4.4%, P = 0.048). A tendency of lower 5y-MFS rate was observed in TNBC compared with in IMPC, in node positive cases (63.8 ± 5.5% vs. 74.8 ± 5.5%, P = 0.053) and in node negative cases (80.1 ± 3.6% vs. 96.2 ± 3.8%, P = 0.052), but it did not reach significance. 5y-OS was similar between IMPC and TNBC (81.9 ± 4.7% vs. 79.8 ± 3.1%, P = 0.475). CONCLUSIONS: IMPC is featured with high rate of lymph node involvement which is strongly associated with high rate of LRR. TNBC is featured with high rate of early distant metastasis without increase of nodal metastases. The survival is still relatively poor even in node negative cases.