Chemotherapy is a primary treatment for breast cancer (BC), yet many patients develop resistance over time. This study aims to identify critical factors contributing to chemoresistance and their underlying molecular mechanisms, with a focus on reversing this resistance. We utilized samples from the Gene Expression Omnibus (GEO) and West China Hospital to identify and validate genes associated with chemoresistance. Functional studies were conducted using MDA-MB-231 and MCF-7 cell lines, involving gain-of-function and loss-of-function approaches. RNA sequencing (RNA-seq) identified potential mechanisms. We examined interactions between DNAJC12, HSP70, and AKT using co-immunoprecipitation (Co-IP) assays and established cell line-derived xenograft (CDX) models for in vivo validations. Boruta analysis of four GEO datasets identified DNAJC12 as highly significant. Patients with high DNAJC12 expression showed an 8 % pathological complete response (pCR) rate, compared to 38 % in the low expression group. DNAJC12 inhibited doxorubicin (DOX)-induced cell death through both ferroptosis and apoptosis. Combining apoptosis and ferroptosis inhibitors completely reversed DOX resistance caused by DNAJC12 overexpression. RNA-seq suggested that DNAJC12 overexpression activated the PI3K-AKT pathway. Inhibition of AKT reversed the DOX resistance induced by DNAJC12, including reduced apoptosis and ferroptosis, restoration of cleaved caspase 3, and decreased GPX4 and SLC7A11 levels. Additionally, DNAJC12 was found to increase AKT phosphorylation in an HSP70-dependent manner, and inhibiting HSP70 also reversed the DOX resistance. In vivo studies confirmed that AKT inhibition reversed DNAJC12-induced DOX resistance in the CDX model. DNAJC12 expression is closely linked to chemoresistance in BC. The DNAJC12-HSP70-AKT signaling axis is crucial in mediating resistance to chemotherapy by suppressing DOX-induced ferroptosis and apoptosis. Our findings suggest that targeting AKT and HSP70 activities may offer new therapeutic strategies to overcome chemoresistance in BC.

Primary pleuropulmonary and mediastinal synovial sarcomas (PPMSSs) are extremely rare. The authors present the largest series in an Asian population. Between 2000 and 2015, 26 genetically confirmed PPMSSs were included. The clinicopathologic features of all of the cases were reviewed. Immunohistochemical staining was carried out using the following antibodies: TLE1, cytokeratin (AE1/AE3), EMA, CD99, Bcl-2, CK7, CD34, S-100 protein, and Ki-67. The chromosomal translocation t(X;18)(p11.2;q11.2) was detected by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). We compared the clinical, pathologic, immunohistochemical, and molecular features of this series with that of the previous series and soft tissue synovial sarcomas. This series included 17 males and nine females. The median age was 36.5 years (range, 16–72 years). The tumors involved the lung (76.9 %), pleura (15.4 %), and mediastinum (7.7 %). The median tumor size was 6 cm (range 2.3 ~ 24 cm). The majority of the tumors were well-circumscribed. The tumors were classified as monophasic (84.6 %), biphasic (3.8 %), and poorly differentiated (11.5 %) types. The tumors were graded as French Federation of Cancer Centers (FNCLCC) grade 2 (62.5 %) and FNCLCC 3 (37.5 %). Diffuse immunostaining for TLE1, BCL-2, and CD99 was identified in 91.7, 95.7, and 56.0 % of the tumors, respectively. Focal positivity was seen with EMA (84.6 %), CK7 (55.6 %), cytokeratin (AE1/AE3) (68.0 %), CD34 (5.0 %), and S-100 protein (21.7 %). A high Ki-67 index (≥10 %) was observed in 91.3 % of the tumors. The fusion transcripts included SS18-SSX1 (15/22, 68.2 %), SS18-SSX2 including variants (6/22, 27.3 %), and SS18-SSX4 (1/22, 4.5 %) fusions. The remaining four cases showed positivity for SS18 rearrangement by FISH. Surgical excision of tumors or lobectomy were performed in 20 patients, and seven of the patients underwent adjuvant therapy. Clinical follow-up was available in 73.1 % cases, with a median follow-up of 12.0 months. The median survival time was 14.5 months. Tumor resection (p = 0.024) and no residual tumor (p = 0.004) were associated with an improved overall survival time. PPMSS is a highly aggressive neoplasm. Extensive surgical resection of the tumor and more effective adjuvant therapy should be advocated. PPMSS must be differentiated from similar diseases.