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Low expression of DJ-1 protein with high expression of its mRNA, which may reflect a secretory expression pattern, is predictive of poor outcome in patients with IDC.

In patients with cancer and Parkinson’s disease, the DJ-1 protein may be secreted into the serum during the impaired response of the underlying cell-protective mechanisms. In order to determine the clinical significance of DJ-1 protein in the sera of breast cancer patients, we examined blood samples from a breast cancer group (n = 180) and a non-cancerous control group (n = 300). Higher levels of DJ-1 were detected in the breast cancer group (mean level, 42.7 ng/mL) than the control group (28.3 ng/mL) by ELISA (P = 0.019). Higher DJ-1 levels were significantly associated with advanced clinical grade, according to the TNM classification, negative hormone receptor status, and high Ki-67 labeling index, of biopsied materials; samples showed low DJ-1 protein expression despite upregulated DJ-1 mRNA. DJ-1 isoforms could be detected clearly in 17 blood samples (from 11 breast cancer patients, and 6 non-cancerous controls) by 2-D gel electrophoresis and immunoblot analysis. The isoform at the pI of 6.3 showed the highest intensity in all 11 cancer cases. Conversely, in the 6 non-cancerous cases, isoforms other than the pI 6.3 isoform were highly expressed, and there was a significant difference in the isoform pattern between breast cancer cases and controls (P = 0.00025). These data indicate that high levels of DJ-1, probably of isoform at pI 6.3, is a candidate serum marker of breast cancer.

Upregulation of DJ-1 mRNA is commonly observed in various human cancers such as ductal carcinoma of the breast, non-small cell carcinoma of the lung, pancreatic duct adenocarcinoma, urinary transitional cell carcinoma, and gynecologic carcinoma. At the protein level, intensity and intracellular localization of DJ-1 expression is varied, and the DJ-1 protein regulates cancer progression, clinical aggressiveness, differentiation, cancer cell morphology, and drug sensitivity. Thus, DJ-1 plays a critical role in cancer. Although DJ-1 has an important role within cancer cells, cancer cells secrete DJ-1 outside the cells. DJ-1 may serve as a tumor marker that can be detected from an early stage in the blood, secretory fluids, ascites, or pleural effusion.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 remains a major global crisis and continues to spread relentlessly around the world. In Japan, the number of infected people has incrementally increased since April 2020. The COVID-19 pandemic has exerted a major impact not only on our daily lives but also on healthcare. As the infection continues to spread, many medical institutions have devoted all efforts to minimize the risk of infection not only for patients but also for medical personnel by prioritizing medical care, reserving treatment, and extending consultation intervals. Cancer treatment is one of the priorities for medical care even during an epidemic infection as there is a concern of decreasing curability or therapeutic effect from postponement. As the COVID-19 situation evolves rapidly, we created an informative triage to provide appropriate medical treatment to breast cancer patients. In this triage, we offer guidance on preparing for the impact of the COVID-19 pandemic in breast cancer patients, prioritizing triage and diagnostic procedures, and providing advice on surgical, radiation, and oncological treatments.

Parkinson's disease is associated with DJ-1/Parkinson protein 7 dysfunction. In contrast, hyperactivity of DJ-1 increases the resistance of cancer cells to apoptosis. Recent genetic studies showed that, in addition to apoptosis pathways, DJ-1 is also involved in cellular defense against reactive oxygen species. The activity of apoptotic and cellular defense pathways is key in determining drug sensitivity. DJ-1 overexpression is associated with various cancers. However, we previously found that there were approximately 50 % patients with breast cancers that expressed low levels of DJ-1 protein, despite mRNA upregulation. Furthermore, low DJ-1 expression was a significant predictor of poor clinical outcome in these patients. This study aimed to determine the association between low DJ-1 protein expression and pathological complete remission (pCR) after neoadjuvant chemotherapy in breast cancer patients. Expression of DJ-1 in pre-therapeutic needle biopsies and surgical specimens obtained from 205 breast cancer cases that received neoadjuvant chemotherapy was determined using immunohistochemistry and in situ hybridization. Chemotherapy comprised epirubicin/cyclophosphamide taxane-based regimens with or without the inclusion of trastuzumab. Univariate and multivariate analyses were used to evaluate the predictive value of DJ-1 on pCR. Low DJ-1 protein expression was detected in 45.3 % (93/205) of all breast cancer cases and in 79.6 % (39/49) of pCR cases, irrespective of maintained mRNA levels. DJ-1 expression [hazard ratio (HR): 1.36; 95 % confidence interval (CI): 1.01-1.84] and HER2 status (HR: 0.84; 95 % CI: 0.62-1.14), in contrast to histological grade, hormone receptors status, Ki-67 labeling index, and intrinsic subtype, were significant predictors of pCR. Low DJ-1 expression predicted pCR in luminal A (P = 0.0004), luminal B (P = 0.0194), and triple negative (P = 0.0143) subtypes breast cancer patients and in patients receiving additional trastuzumab treatment (P = 0.008). In conclusion, low DJ-1 protein expression is a significant predictor of pCR after neoadjuvant chemotherapy in breast cancer patients.

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