• BMB Reports
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• 제51권12호
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• pp.642-647
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• 2018

Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitination process, is involved in development of various cancers. However, its role in lung adenocarcinoma, has not been well elucidated. In this report, we attempted to investigate expression and function of UBE2S in lung adenocarcinoma. Up-regulation of UBE2S at mRNA, and protein level, was observed in human cancer tissues and lung adenocarcinoma cells. Higher UBE2S expression correlated with poorer prognosis of lung adenocarcinoma patients. UBE2S expression was efficiently suppressed by lentivirus-mediated shRNA strategy in A549 cells, and UBE2S silencing led to reduced cell proliferation, colony formation, and enhanced apoptosis. Inverse results were observed, in UBE2S over-expressed H1299 cells. Microarray analysis indicated that a large number of genes were regulated by UBE2S, and p53 signaling pathway may be critical, to the role of UBE2S in cancer development. Together, UBE2S could be a potential target for lung adenocarcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2021-2023
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• 2012

Purpose: DBC2 (Deleted in Breast Cancer 2) has been indicated to be a tumor suppressor gene in many cancers including lung adenocarcinoma recently. In this study, we aimed to explore the expression status of DBC2 in different subtypes of lung adenocarcinoma (from pre-invasive to invasive lesions), and to determine if downregulation becomes more marked with pathological progression. Methods: We collected 172 tissue samples from different subtypes of lung adenocarcinoma and investigated the frequency of DBC2 loss by immunohistochemistry. Results: Our results indicated that DBC2 downregulation is a relatively frequent event in lung adenocarcinoma. Moreover, as the adenocarcinoma subtype turns to be more invasive, more downregulation occurred. Conclusion: We conclude that loss of DBC2 expression is an early and progressive event in the pathogenesis of lung adenocarcinoma. Positive DBC2 immunohistochemistry may become an indicator for early stage disease and better prognosis of lung adenocarcinomas.

• Tuberculosis and Respiratory Diseases
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• 제73권1호
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• pp.61-66
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• 2012

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (extranodal MZL) is a distinct subgroup of non-Hodgkin's lymphoma. Pulmonary extranodal MZL is a rare entity and accounts for less than 0.5% of primary pulmonary malignancies. Only a few cases of simultaneous occurrence of lung cancer and pulmonary extranodal MZL have been reported. A 60-year-old woman was referred to our hospital with a pulmonary nodule. She was diagnosed with lung adenocarcinoma by percutaneous needle biopsy. The protrusions into the left main bronchus were found by accident while performing bronchoscopy during lung cancer evaluation. The bronchial lesions were diagnosed as extranodal MZL. Although the patient underwent surgical resection for the lung adenocarcinoma, the pulmonary extranodal MZL was left untreated; it was monitored during follow-up visits. To our knowledge, this is the first report of synchronous lung adenocarcinoma and primary extranodal MZL of the main bronchus.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3857-3860
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• 2015

Background: Recent studies revealed a relationship between ground-glass opacity (GGO) ratio on computed tomography (CT) and serum carcinoembryonic antigen (CEA) level in lung adenocarcinoma. Since an association between lepidic histologic pattern and GGO is well accepted, we investigated the link between histologic subtype and serum CEA level in resected lung adenocarcinoma. Materials and Methods: One hundred and eighty-one consecutive patients with resected lung adenocarcinoma were studied retrospectively. The histologic subtype was subdivided into 2 groups: lepidic dominant histologic subtype, including adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic predominant invasive adenocarcinoma versus other subtypes. Results: The 5-year survival of patients with s high serum CEA level was significantly more unfavorable than that with normal levels. Similarly, there was also a relationship between the patient survival and histologic subtype, with favorable survival found in patients with the lepidic dominant histologic subtype. There was a significant relationship between serum CEA level and lepidic dominant histologic subtype overall and in p-stage I patients. Conclusions: Lung adenocarcinomas with non-lepidic dominant histologic subtype are associated with high serum CEA levels.

• Oncology Letters
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• 제41권6호
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• pp.3305-3312
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• 2019

Histone H2B monoubiquitination has been shown to play critical roles in diverse cellular processes including DNA damage response. Although recent data indicate that H2B monoubiquitination is strongly connected with tumor progression and regulation, the implications of this modification in lung adenocarcinoma are relatively unknown. In the present study, we demonstrated the clinical implication of H2B monoubiquitination and the potential role of tumor necrosis factor receptor-associated factor-interacting protein (TRAIP) in regulating its modification in lung adenocarcinoma. Immunohistochemical analysis showed that H2B monoubiquitination was significantly downregulated in 68 human lung adenocarcinoma patient samples compared to their normal adjacent tissues. Depletion of TRAIP by specific siRNA treatment markedly decreased ionizing radiation (IR)-induced H2B monoubiquitination. In addition, deletion mutants without RING domain or C-terminus of TRAIP diminished the ability to induce H2B monoubiquitination at lysine 120. Notably, the nuclear expression of TRAIP was positively related with H2B monoubiquitination levels in patients with lung adenocarcinoma. Furthermore, statistical analysis indicated that low levels of both TRAIP and H2B monoubiquitination, not each alone, in patients with lung adenocarcinoma were strongly correlated with poor survival. Taken together, these results suggest that TRAIP is a novel regulator of H2B monoubiquitination in DNA damage response and cancer development in lung adenocarcinoma.

• Tuberculosis and Respiratory Diseases
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• 제83권1호
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• pp.61-70
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• 2020

Background: Circulating tumor cells (CTCs) are frequently detected in patients with advanced-stage malignant tumors and could act as a predictor of poor prognosis. However, there is a paucity of data on the relationship between CTC number and primary tumor volume in patients with lung cancer. Therefore, our study aimed to evaluate the relationship between CTC number and primary tumor volume in patients with lung adenocarcinoma. Methods: We collected blood samples from 21 patients with treatment-naive lung adenocarcinoma and 73 healthy individuals. To count CTCs, we used a CTC enrichment method based on fluid-assisted separation technology. We compared CTC numbers between lung adenocarcinoma patients and healthy individuals using propensity score matching, and performed linear regression analysis to analyze the relationship between CTC number and primary tumor volume in lung adenocarcinoma patients. Results: CTC positivity was significantly more common in lung adenocarcinoma patients than in healthy individuals (p<0.001). The median primary tumor volume in CTC-negative and CTC-positive patients was 10.0 ㎤ and 64.8 ㎤, respectively. Multiple linear regression analysis showed that the number of CTCs correlated with primary tumor volume in lung adenocarcinoma patients (β=0.903, p=0.002). Further subgroup analysis showed a correlation between CTC number and primary tumor volume in patients with distant (p=0.024) and extra-thoracic (p=0.033) metastasis (not in patients with distant metastasis). Conclusion: Our study showed that CTC numbers may be associated with primary tumor volume in lung adenocarcinomas patients, especially in those with distant metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6519-6522
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• 2013

Background: Genetic polymorphisms of TP63 have been suggested to influence susceptibility to lung adenocarcinoma development in East Asian populations. This study aimed to investigate the relationship between common polymorphisms in the TP63 gene and the risk of lung adenocarcinoma, as well as interactions of the polymorphisms with environmental risk factors in Chinese non-smoking females. Methods: A case-control study of 260 cases and 318 controls was conducted. Data concerning demographic and risk factors were obtained for each subject. The genetic polymorphisms were determined by Taqman real-time PCR and statistical analyses were performed using SPSS software. Results: For 10937405, carriers of the CT genotype or at least one T allele (CT/TT) had lower risks of lung adenocarcinoma compared with the homozygous wild CC genotype in Chinese nonsmoking females (adjusted ORs were 0.68 and 0.69, 95%CIs were 0.48-0.97 and 0.50-0.97, P values were 0.033 and 0.030, respectively). Allele comparison showed that the T allele of rs10937405 was associated with a decreased risk of lung adenocarcinoma with an OR of 0.78 (95%CI=0.60-1.01, P=0.059). Our results showed that exposure to cooking oil fumes was associated with increased risk of lung adenocarcinoma in Chinese nonsmoking females (adjusted OR=1.58, 95%CI=1.11-2.25, P=0.011). However, we did not observe a significant interaction of cooking oil fumes and TP63 polymorphisms. Conclusion: TP63 polymorphism might be a genetic susceptibility factor for lung adenocarcinoma in Chinese non-smoking females, but no significant interaction was found with cooking oil fume exposure.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6281-6286
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• 2013

Background: To further investigate the molecular basis of lung cancer development, we utilize a microarray to identify differentially expressed genes associated with various TNM stages of adenocarcinoma, a subtype with increasing incidence in recent years in China. Methods: A 35K oligo gene array, covering about 25,100 genes, was used to screen differentially expressed genes among 90 tumor samples of lung adenocarcinoma in various TNM stages. To verify the gene array data, three genes (Zimp7, GINS2 and NAG-1) were confirmed by real-time RT-PCR in a different set of samples from the gene array. Results: First, we obtained 640 differentially expressed genes in lung adenocarcinomas compared to the surrounding normal lung tissues. Then, from the 640 candidates we identified 10 differentially expressed genes among different TNM stages (Stage I, II and IIIA), of which Zimp7, GINS2 and NAG-1 genes were first reported to be present at a high level in lung adenocarcinoma. The results of qRT-PCR for the three genes were consistent with those from the gene array. Conclusions: We identified 10 candidate genes associated with different TNM stages in lung adenocarcinoma in the Chinese population, which should provide new insights into the molecular basis underlying the development of lung adenocarcinoma and may offer new targets for the diagnosis, therapy and prognosis prediction.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3191-3194
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• 2014

Adenocarcinoma of lung has high incidence and a poor prognosis, woith chemotherapy as the main therapeutic tool, most commonly with cisplatin. However, chemotherapy resistance develops in the majority of patients during clinic treatment. Mechanisms of resistance are complex and still unclear. Although annexin play important roles in various tumor resistance mechanisms, their actions in cisplatin-resistant lung adenocarcinoma remain unclear. Preliminary studies by our group found that in cisplatin-resistant lung cancer A549 cells and lung adenocarcinoma tissues, both mRNA and protein expression of annexins A1, A2 and A3 is increased. Using a library of annexin A1, A2 and A3 targeting combined molecules already established by ourselves we found that specific targeting decreased cisplatin-resistance. Taken together, the underlined effects of annexins A1, A2 and A3 on drug resistance and suggest molecular mechanisms in cisplatin-resistant A549 cells both in vivo and in vitro. Furthermore, the study points to improved research on occurrence and development of lung adenocarcinoma, with provision of effective targets and programmes for lung adenocarcinoma therapy in the clinic.

• Clinical and Experimental Pediatrics
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• 제61권1호
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• pp.30-34
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• 2018

Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation, is a rare developmental lung abnormality associated with rhabdomyosarcoma, pleuropulmonary blastoma, and mucinous adenocarcinoma of the lung. We report an unusual case of a 10-day-old male newborn with a left lower lobe pulmonary cyst who underwent lobectomy, which revealed type II CPAM complicated by multifocal mucinous adenocarcinoma. KRAS sequencing revealed a somatic mutation in Codon12 ($GGT{\rightarrow}GAT$), suggesting the development of a mucinous adenocarcinoma in the background of mucinous metaplasia. Mucinous adenocarcinoma is the most common lung tumor associated with CPAM, but it generally occurs in older children and adults. Further, all cases in the literature are of type I CPAM. This case in a neonate indicates that malignant transformation can occur very early in type II CPAM.