PMC9299075_01
Images of the left renal carcinoma and the changes of metastases when the patient took nilapanib. (A) Computed tomography image examination showed an enhancing mass measuring 9.3 cm x 8.2 cm x 7.7 cm (red arrow) in the left renal. (B) Magnetic resonance image examination revealed a significantly reduced mass [7.3 cm x 6.8 cm x 7.0 cm (red arrow)] in the left renal after sorafenib-targeted therapy for 14 months. (C) Before nilapanib; (D) After nilapanib for 2 months; (E) After nilapanib for 4 months; (F) After nilapanib for 5 months. Chest CT showed metastases in the lungs (red circle) and atelectasis in the left lung (green arrows) due to the tumor invasion of the left bronchus, received continuous remission in the first 4 months after nilapanib (C-E). (F) showed that new metastases appeared in the hilus of the left lung, resulting in atelectasis.
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Computed tomography (CT) revealed an enhancing mass measuring 9.3 x 8.2 x 7.7 cm in the left renal ( Figure 1A ), multiple enlarged lymph nodes in the retroperitoneal, and a quasi-circular mass (maximum size 3.0 cm) in the liver but normal alpha-fetoprotein levels (1.54 ng/ml; normal <5.0 ng/ml). In July 2019, after the patient achieved a partial response confirmed by magnetic resonance imaging (MRI) after sorafenib-targeted therapy for 14 months ( Figure 1B ), cytoreductive nephrectomy (CN) was further performed. Cooperative Oncology Group and an 8-grade Visual Analogue Scale (VAS) Pain. Chest CT showed atelectasis in the left lung due to the tumor invasion of the left bronchus and metastases in the right lung ( Figure 1C ). To our excited, the patient displayed a partial response in both lungs after niraparib for 2 months ( Figure 1D ). In the following 2 months, the patient received continuous remission ( Figure 1E ). However, in March 2021, 5 months after taking niraparib, new metastases appeared in the brain and the hilus of the left lung, resulting in atelectasis ( Figure 1F ).
The patient's detailed treatment process and the tumor marker changes. The curve showed that the tumor markers is still in the normal level upon first diagnosis. However, they were already higher than normal when the patient was admitted in our hospital. However, after taking nilapanib, the tumor markers returned to normal again. The blue arrow showed the detailed medication information along the treatment. On the other hand, there is still the lack of specific tumor markers for ccRCC. The changes of LDH and CEA may be inconsistent with changes in the tumors.
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The Lactate Dehydrogenase (LDH) and Carcino-Embryonic Antigen (CEA), which elevated to abnormal when the patient admitted to our hospital, returned to normal again ( Figure 2 ).
Frequencies of BAP1 alteration across cancer types and mechanism of BAP1 in DNA damage repairment. (A)
BAP mutations most commonly occurred in pleural mesotheliomas, cholangiocarcinoma, ocular melanoma, and renal clear cell carcinoma from a total of 32 large-scale TCGA PanCancer Atlas Studies that contained 10,967 samples. (B) Mechanism of BAP1 in DNA damage repairment. BRCA1/BARD1 complex is an E3 ubiquitin ligase and interacts with the recombinase RAD51 to regulate the homologous recombination repairment. BAP1 can be recruited to DNA damage loci and bind to the BRCA1/BARD1 complex. By this, BAP1 can inhibit the E3 ligase activity of BRCA1/BARD1 to protect against additional ubiquitination and deubiquitinate preexisting ubiquitin chains (bent arrow).
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TCGA PanCancer Atlas Studies containing 10,967 samples. The data from these publications are clustered for analysis as shown in  Figure 3A .