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Kimihiro Shimizu
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P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.03-09 - Atypical Ubiquitin as a Molecular Target in Lung Cancer (ID 2993)
09:45 - 18:00 | Author(s): Kimihiro Shimizu
- Abstract
Background
Atypical ubiquitin is a newly identified type of posttranslational modification. Although the role of most atypical ubiquitins remains unknown, linear ubiquitin (M1Ub) was shown to regulate activation of NFkB signaling. M1Ub is specifically assembled by an enzyme complex known as linear ubiquitin chain assembly complex (LUBAC), composed of the proteins HOIP, HOIL-1L, and Sharpin. Since the role of M1Ub and LUBAC in lung cancer is unclear, our study aimed to identify the potential value of LUBAC as a molecular target in lung cancer.
Method
We searched for lung cancer cell lines with high LUBAC expression. We inhibited LUBAC activity by siRNA or CRISPR/Cas9 and analyzed effect on tumor proliferation, migration, and tumor formation. We also analyzed prognostic impact of LUBAC expression in lung cancer patients and searched for mutations known to activate LUBAC activity.
Result
Several adenocarcinoma cell lines showed high LUBAC expression. LUBAC inhibition resulted in lower proliferation, migration, and tumor formation, partly via activation of NFkB and ERK signaling. LUBAC knockdown also showed increased apoptosis via activation of caspases. The expression of LUBAC was a significant prognostic factor in survival of lung adenocarcinoma patients. Few patients were identified with a mutation of HOIP related to LUBAC formation, resulting in high LUBAC expression.
Conclusion
We identified that LUBAC components regulate proliferation, migration, and apoptosis in certain lung cancer cell lines. LUBAC expression was also associated with prognosis of lung cancer. LUBAC components may become a potential treatment target in lung cancer.
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P2.05 - Interventional Diagnostic/Pulmonology (ID 168)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Interventional Diagnostics/Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.05-09 - FDG-PET for Predicting Acute Exacerbation of Interstitial Pneumonia After Lung Cancer Surgery (ID 553)
10:15 - 18:15 | Presenting Author(s): Kimihiro Shimizu
- Abstract
Background
Acute exacerbation of interstitial pneumonia (IP) is a critical complication after lung cancer resection. Although FDG-PET is commonly used for preoperative assessment of lung cancer, its role for predicting acute exacerbation of IP after lung cancer resection is unclear.
Method
We retrospectively analyzed data of lung cancer patients that underwent surgical resection at Gunma University Hospital between 2008 and 2016. We analyzed data from patients with IP based on computed tomography findings (IP group). As control, we also analyzed data in patients with no underlying lung disease (normal group) and with emphysema (emphysema group). Patients with sufficient FDG-PET data were selected and a final of 92 patients in the IP group, 21 patients in the normal group, and 20 patients in the emphysema group were enrolled in analysis. The FDG-PET values were measured at the aorta and the basal lung. Aorta values were used for reference and we calculated the basal/aorta ratio and analyzed correlation with preoperative factors, including acute exacerbation of IP and mortality.
Result
The basal/aorta ratio was significantly higher in the IP group when compared to normal and emphysema group (both p<0.01). The incidence of acute exacerbation of IP was 10.9%, and the sensitivity and specificity of basal/aorta value for predicting acute exacerbation of IP were 70.0% and 77.2%, respectively (cutoff of basal/aorta ratio at 0.833). Patients were further classified into high basal/aorta ratio group (n=35) and low basal/aorta ratio group (n=57). The incidence of acute exacerbation of IP was significantly higher in the high basal/aorta ratio group (p=0.035). We also compared the value of basal/aorta ratio in comparison to the existing IP acute exacerbation score. Patients were divided into low score (less than 10, n=64) and high score (higher or equal to 11, n=28). The sensitivity and specificity for predicting acute exacerbation of IP was 60.0% and 82.3%, respectively, and there was no significant difference between the high and low score groups (p=0.062).
Conclusion
The basal/aorta ratio of FDG-PET values showed a significant correlation with the incidence of postoperative acute exacerbation of IP. Since FDG-PET is commonly used for preoperative assessment of lung cancer in Japan, it may be used not only for lung cancer staging but also for surgical indication in IP patients with lung cancer by preoperatively detecting patients at high risk for acute exacerbation.