Pub Date : 2024-06-01Epub Date: 2024-05-08DOI: 10.1111/1759-7714.15314
Yi Xu, Shiyu Duan, Wen Ye, Zhousan Zheng, Jiaxing Zhang, Ying Gao, Sheng Ye
Background: Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive.
Methods: Western blotting, quantitative real-time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan-Meier curves were employed for survival analysis. CCK-8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA-sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP-GFP-LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2-interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability.
Results: The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki-67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy-related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17.
Conclusions: These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.
{"title":"SLC34A2 promotes cell proliferation by activating STX17-mediated autophagy in esophageal squamous cell carcinoma.","authors":"Yi Xu, Shiyu Duan, Wen Ye, Zhousan Zheng, Jiaxing Zhang, Ying Gao, Sheng Ye","doi":"10.1111/1759-7714.15314","DOIUrl":"10.1111/1759-7714.15314","url":null,"abstract":"<p><strong>Background: </strong>Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive.</p><p><strong>Methods: </strong>Western blotting, quantitative real-time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan-Meier curves were employed for survival analysis. CCK-8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA-sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP-GFP-LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2-interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability.</p><p><strong>Results: </strong>The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki-67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy-related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17.</p><p><strong>Conclusions: </strong>These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-12DOI: 10.1111/1759-7714.15328
Ni Liu, Qi Zheng, Yuqing Zhang, Huimin Wang, Zhihui Zhang, Long He, Chenxi Wei, Handai Xia, Yanguo Liu, Xiuwen Wang
Background: Cancer stem cells (CSCs) are a specific subpopulation of cancer cells with the ability of self-renewal, infinite proliferation, multidifferentiation and tumorigenicity, and play critical roles in cancer progression and treatment resistance. CSCs are tightly regulated by the tumor microenvironment, such as hypoxia; however, how hypoxia regulates CSCs in non-small cell lung cancer (NSCLC) remains unclear.
Methods: The proportion of ALDHhi cells was examined using the Aldefluor assay. Tankyrase inhibitor XAV939 and siRNA were used to inhibit β-catenin while pcDNA3-β-catenin (S33Y) plasmid enhanced the expression of β-catenin. Western blot was administered for protein detection. The mRNA expression was measured by quantitative real-time PCR.
Results: We found that hypoxia led to an increase in the proportion of ALDHhi cells in lung squamous carcinoma (LUSC) H520 cells, while causing a decrease in the ALDHhi cell proportion in lung adenocarcinoma (LUAD) A549 cells. Similarly, β-catenin expression was upregulated in H520 cells but downregulated in A549 cells upon exposure to hypoxia. Mechanically, the proportion of ALDHhi cells in both cell lines was decreased by β-catenin inhibitor or siRNA knockdown, whereas increased after β-catenin overexpression. Furthermore, hypoxia treatment suppressed E-cadherin expression in H520 cells and enhanced N-cadherin and β-catenin expression, while this effect was completely opposite in A549 cells.
Conclusion: The hypoxia-EMT-β-catenin axis functions as an important regulator for the proportion of CSCs in NSCLC and could potentially be explored as therapeutic targets in the future.
背景:癌症干细胞(CSCs)是癌细胞中的一个特殊亚群,具有自我更新、无限增殖、多分化和致瘤能力,在癌症进展和耐药性中发挥着关键作用。CSCs受缺氧等肿瘤微环境的严格调控,但缺氧如何调控非小细胞肺癌(NSCLC)中的CSCs仍不清楚:方法:使用醛氟试验检测ALDHhi细胞的比例。方法:使用Aldefluor试验检测ALDHhi细胞的比例,使用Tankyrase抑制剂XAV939和siRNA抑制β-catenin,同时使用pcDNA3-β-catenin (S33Y)质粒增强β-catenin的表达。蛋白检测采用 Western 印迹法。结果发现,缺氧会导致β-catenin的表达量增加:结果:我们发现缺氧导致肺鳞癌(LUSC)H520 细胞中 ALDHhi 细胞比例增加,而导致肺腺癌(LUAD)A549 细胞中 ALDHhi 细胞比例减少。同样,β-catenin的表达在H520细胞中上调,但在暴露于缺氧的A549细胞中下调。从机理上讲,β-catenin抑制剂或siRNA敲除后,两种细胞系中ALDHhi细胞的比例都会降低,而β-catenin过表达后,ALDHhi细胞的比例会升高。此外,缺氧处理抑制了H520细胞中E-cadherin的表达,增强了N-cadherin和β-catenin的表达,而这一效应在A549细胞中完全相反:结论:缺氧-EMT-β-catenin轴是NSCLC中造血干细胞比例的重要调节因子,未来有可能成为治疗靶点。
{"title":"Hypoxia differently regulates the proportion of ALDH<sup>hi</sup> cells in lung squamous carcinoma H520 and adenocarcinoma A549 cells via the Wnt/β-catenin pathway.","authors":"Ni Liu, Qi Zheng, Yuqing Zhang, Huimin Wang, Zhihui Zhang, Long He, Chenxi Wei, Handai Xia, Yanguo Liu, Xiuwen Wang","doi":"10.1111/1759-7714.15328","DOIUrl":"10.1111/1759-7714.15328","url":null,"abstract":"<p><strong>Background: </strong>Cancer stem cells (CSCs) are a specific subpopulation of cancer cells with the ability of self-renewal, infinite proliferation, multidifferentiation and tumorigenicity, and play critical roles in cancer progression and treatment resistance. CSCs are tightly regulated by the tumor microenvironment, such as hypoxia; however, how hypoxia regulates CSCs in non-small cell lung cancer (NSCLC) remains unclear.</p><p><strong>Methods: </strong>The proportion of ALDH<sup>hi</sup> cells was examined using the Aldefluor assay. Tankyrase inhibitor XAV939 and siRNA were used to inhibit β-catenin while pcDNA3-β-catenin (S33Y) plasmid enhanced the expression of β-catenin. Western blot was administered for protein detection. The mRNA expression was measured by quantitative real-time PCR.</p><p><strong>Results: </strong>We found that hypoxia led to an increase in the proportion of ALDH<sup>hi</sup> cells in lung squamous carcinoma (LUSC) H520 cells, while causing a decrease in the ALDH<sup>hi</sup> cell proportion in lung adenocarcinoma (LUAD) A549 cells. Similarly, β-catenin expression was upregulated in H520 cells but downregulated in A549 cells upon exposure to hypoxia. Mechanically, the proportion of ALDH<sup>hi</sup> cells in both cell lines was decreased by β-catenin inhibitor or siRNA knockdown, whereas increased after β-catenin overexpression. Furthermore, hypoxia treatment suppressed E-cadherin expression in H520 cells and enhanced N-cadherin and β-catenin expression, while this effect was completely opposite in A549 cells.</p><p><strong>Conclusion: </strong>The hypoxia-EMT-β-catenin axis functions as an important regulator for the proportion of CSCs in NSCLC and could potentially be explored as therapeutic targets in the future.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: To determine the safety and efficacy of robot-assisted minimally invasive esophagectomy (RAMIE) for locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoimmunotherapy (NCI).
Methods: Data from patients who underwent RAMIE between January 2020 and June 2022 were retrospectively analyzed. The oncological and operative outcomes of the NCI and surgery-only (S) groups were compared by both unmatched and 1:1 propensity score-matched (PSM) analysis.
Results: A total of 201 patients with ESCC who underwent three-incision RAMIE were included in this study (143 patients in the S group and 58 patients in the NCI group). Of the 58 patients who underwent NCI, a pathologically complete response (pCR) (ypT0N0) was identified in 14 (24.1%) patients. The patients in the NCI group were younger than those in the S group (p = 0.017), and had more advanced cT (p < 0.001) and cN stage diseases (p = 0.002). After 1:1 PSM of the confounders, 55 patients were allocated to each of the NCI and S groups. No significant differences were found in oncological and operative results, including surgical blood loss, operative time, and lymph node harvest (all p > 0.05). However, the NCI group exhibited a lower rate of pulmonary complications than the S group (3.6% vs. 14.5%, p = 0.047). No significant difference between the groups was found for other complications (all p > 0.05).
Conclusion: These findings indicate that NCI could result in a high pCR rate without increased complications in locally advanced ESCC. RAMIE is safe and feasible in patients with ESCC after NCI.
背景:目的:确定新辅助化疗免疫疗法(NCI)后机器人辅助微创食管切除术(RAMIE)治疗局部晚期食管鳞状细胞癌(ESCC)的安全性和有效性:回顾性分析了2020年1月至2022年6月期间接受RAMIE的患者数据。方法:对2020年1月至2022年6月期间接受RAMIE治疗的患者数据进行回顾性分析,通过非匹配和1:1倾向评分匹配(PSM)分析比较NCI组和单纯手术组(S)的肿瘤学和手术结果:本研究共纳入了201例接受三切口RAMIE手术的ESCC患者(S组143例,NCI组58例)。在接受NCI治疗的58名患者中,14名患者(24.1%)获得了病理完全反应(pCR)(ypT0N0)。与 S 组相比,NCI 组患者更年轻(p = 0.017),cT 更晚期(p 0.05)。不过,NCI 组的肺部并发症发生率低于 S 组(3.6% 对 14.5%,P = 0.047)。在其他并发症方面,两组之间没有发现明显差异(P均大于0.05):结论:这些研究结果表明,NCI可为局部晚期ESCC带来较高的pCR率,同时不会增加并发症。对于接受NCI治疗的ESCC患者,RAMIE是安全可行的。
{"title":"Neoadjuvant chemoimmunotherapy followed by robot esophagectomy has no effect on short-term results compared with surgery alone.","authors":"Feng Guo, Xu Zhang, Fangdong Zhao, Hongjing Jiang, Xiaofeng Duan","doi":"10.1111/1759-7714.15334","DOIUrl":"10.1111/1759-7714.15334","url":null,"abstract":"<p><strong>Background: </strong>To determine the safety and efficacy of robot-assisted minimally invasive esophagectomy (RAMIE) for locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoimmunotherapy (NCI).</p><p><strong>Methods: </strong>Data from patients who underwent RAMIE between January 2020 and June 2022 were retrospectively analyzed. The oncological and operative outcomes of the NCI and surgery-only (S) groups were compared by both unmatched and 1:1 propensity score-matched (PSM) analysis.</p><p><strong>Results: </strong>A total of 201 patients with ESCC who underwent three-incision RAMIE were included in this study (143 patients in the S group and 58 patients in the NCI group). Of the 58 patients who underwent NCI, a pathologically complete response (pCR) (ypT0N0) was identified in 14 (24.1%) patients. The patients in the NCI group were younger than those in the S group (p = 0.017), and had more advanced cT (p < 0.001) and cN stage diseases (p = 0.002). After 1:1 PSM of the confounders, 55 patients were allocated to each of the NCI and S groups. No significant differences were found in oncological and operative results, including surgical blood loss, operative time, and lymph node harvest (all p > 0.05). However, the NCI group exhibited a lower rate of pulmonary complications than the S group (3.6% vs. 14.5%, p = 0.047). No significant difference between the groups was found for other complications (all p > 0.05).</p><p><strong>Conclusion: </strong>These findings indicate that NCI could result in a high pCR rate without increased complications in locally advanced ESCC. RAMIE is safe and feasible in patients with ESCC after NCI.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-12DOI: 10.1111/1759-7714.15302
Ying Meng, Hua Zhang, Mingling Xu, Zhenzhen Chen, Lei Wei
Background: Lung cancer, with high morbidity and mortality, is the commonest respiratory system neoplasm, which seriously endangers the life safety of patients. In this study, the effect of PRPS2 on cell progression was preliminarily investigated.
Methods: Immunohistochemical staining, western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to verify the expression level of PRPS2 in lung cancer. Lung cancer cell lines with stable downregulation of PRPS2 were constructed in A549 cells and NCIH460 cells. The function of PRPS2 silencing on the proliferation ability was verified by the EdU and cell colony formation experiment. Scratch and transwell tests were conducted to verify the role of PRPS2 silencing on the migratory and invasive ability of cells. The impact of PRPS2 silencing on cell apoptosis and cell cycle was verified by flow cytometry test. The effects of PRPS2 silencing on apoptosis-associated proteins were assessed by western blot assay. The function of PRPS2 silencing on tumor growth in vivo was studied through xenograft tumor experiment.
Results: In comparison with normal tissues, PRPS2 was upregulated in lung cancer tissues. PRPS2 knockdown notably hindered the migratory ability, invasive ability and proliferation, but accelerated cell apoptosis. In vivo experiments confirmed that PRPS2 silencing blocked the growth of transplanted tumors.
Conclusion: In lung cancer, PRPS2 silencing suppressed the malignant progression, indicating that PRPS2 might be a novel biomarker for lung cancer treatment and diagnosis.
{"title":"Regulatory mechanism and expression level of PRPS2 in lung cancer.","authors":"Ying Meng, Hua Zhang, Mingling Xu, Zhenzhen Chen, Lei Wei","doi":"10.1111/1759-7714.15302","DOIUrl":"10.1111/1759-7714.15302","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer, with high morbidity and mortality, is the commonest respiratory system neoplasm, which seriously endangers the life safety of patients. In this study, the effect of PRPS2 on cell progression was preliminarily investigated.</p><p><strong>Methods: </strong>Immunohistochemical staining, western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to verify the expression level of PRPS2 in lung cancer. Lung cancer cell lines with stable downregulation of PRPS2 were constructed in A549 cells and NCIH460 cells. The function of PRPS2 silencing on the proliferation ability was verified by the EdU and cell colony formation experiment. Scratch and transwell tests were conducted to verify the role of PRPS2 silencing on the migratory and invasive ability of cells. The impact of PRPS2 silencing on cell apoptosis and cell cycle was verified by flow cytometry test. The effects of PRPS2 silencing on apoptosis-associated proteins were assessed by western blot assay. The function of PRPS2 silencing on tumor growth in vivo was studied through xenograft tumor experiment.</p><p><strong>Results: </strong>In comparison with normal tissues, PRPS2 was upregulated in lung cancer tissues. PRPS2 knockdown notably hindered the migratory ability, invasive ability and proliferation, but accelerated cell apoptosis. In vivo experiments confirmed that PRPS2 silencing blocked the growth of transplanted tumors.</p><p><strong>Conclusion: </strong>In lung cancer, PRPS2 silencing suppressed the malignant progression, indicating that PRPS2 might be a novel biomarker for lung cancer treatment and diagnosis.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-06DOI: 10.1111/1759-7714.15321
Wei Fu, Lixin Liu, Suiju Tong
Background: Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood.
Methods: Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase-like 3 (METTL3), and insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)-qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay.
Results: BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR-treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A-IGF2BP3-dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo.
Conclusion: BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3-mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment.
{"title":"Berberine inhibits the progression of breast cancer by regulating METTL3-mediated m6A modification of FGF7 mRNA.","authors":"Wei Fu, Lixin Liu, Suiju Tong","doi":"10.1111/1759-7714.15321","DOIUrl":"10.1111/1759-7714.15321","url":null,"abstract":"<p><strong>Background: </strong>Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood.</p><p><strong>Methods: </strong>Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase-like 3 (METTL3), and insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)-qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay.</p><p><strong>Results: </strong>BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR-treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A-IGF2BP3-dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo.</p><p><strong>Conclusion: </strong>BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3-mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-08DOI: 10.1111/1759-7714.15327
Wei Guo, Tan Wang, Qilin Huai, Lei Guo, Xiaobing Wang, Jie He
Background: Alterations in epigenetic factors are recognized as key contributors to the emergence of human cancer. The active and reversible alteration of N6-methyladenosine (m6A) RNA is crucial for controlling gene activity and determining cellular destiny. Even with these insights, the triggering of KIAA1429 (also called VIRMA) and its role in lung adenocarcinoma (LUAD) is mostly unclear. As a result, the objective of this study was to elucidate how KIAA1429 contributes to cancer development in LUAD.
Methods: This study utilized multiple methods for investigation, encompassing the in vitro functional examination of KIAA1429 in lung adenocarcinoma cells, transcriptome sequencing, methylation RNA immunoprecipitation sequencing (MeRIP-seq), as well as RNA stability tests to ascertain the half-life and stability of the target genes.
Results: The results indicated that modifying the expression of KIAA1429 regulated the proliferation and metastasis of LUAD. By employing transcriptome sequencing alongside MeRIP-seq analysis, the research pinpointed genes affected by m6A alterations triggered by KIAA1429. In a more detailed manner, it was discovered that KIAA1429 plays a regulatory role in the expression of ARHGAP30. Suppressing KIAA1429 results in reduced m6A levels in the mRNA of the target gene ARHGAP30, boosting its stability and expression, thus inhibiting tumor proliferation and metastasis.
Conclusion: This study revealed the activation mechanism and pivotal function of KIAA1429 in LUAD tumor development, paving the way for molecular-based interventions for LUAD.
{"title":"KIAA1429 regulates lung adenocarcinoma proliferation and metastasis through the PI3K/AKT pathway by modulating ARHGAP30 expression.","authors":"Wei Guo, Tan Wang, Qilin Huai, Lei Guo, Xiaobing Wang, Jie He","doi":"10.1111/1759-7714.15327","DOIUrl":"10.1111/1759-7714.15327","url":null,"abstract":"<p><strong>Background: </strong>Alterations in epigenetic factors are recognized as key contributors to the emergence of human cancer. The active and reversible alteration of N6-methyladenosine (m6A) RNA is crucial for controlling gene activity and determining cellular destiny. Even with these insights, the triggering of KIAA1429 (also called VIRMA) and its role in lung adenocarcinoma (LUAD) is mostly unclear. As a result, the objective of this study was to elucidate how KIAA1429 contributes to cancer development in LUAD.</p><p><strong>Methods: </strong>This study utilized multiple methods for investigation, encompassing the in vitro functional examination of KIAA1429 in lung adenocarcinoma cells, transcriptome sequencing, methylation RNA immunoprecipitation sequencing (MeRIP-seq), as well as RNA stability tests to ascertain the half-life and stability of the target genes.</p><p><strong>Results: </strong>The results indicated that modifying the expression of KIAA1429 regulated the proliferation and metastasis of LUAD. By employing transcriptome sequencing alongside MeRIP-seq analysis, the research pinpointed genes affected by m6A alterations triggered by KIAA1429. In a more detailed manner, it was discovered that KIAA1429 plays a regulatory role in the expression of ARHGAP30. Suppressing KIAA1429 results in reduced m6A levels in the mRNA of the target gene ARHGAP30, boosting its stability and expression, thus inhibiting tumor proliferation and metastasis.</p><p><strong>Conclusion: </strong>This study revealed the activation mechanism and pivotal function of KIAA1429 in LUAD tumor development, paving the way for molecular-based interventions for LUAD.</p>","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). METHODS This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. RESULTS The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001). CONCLUSION HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline 18F-FDG PET/CT might be promising to identify patients with poor prognosis.
{"title":"Intratumoral metabolic heterogeneity by 18F-FDG PET/CT to predict prognosis for patients with thymic epithelial tumors.","authors":"Fangfang Chao, Ran Wang, Xingmin Han, Wenpeng Huang, Ruihua Wang, Yanxia Yu, Xuyang Lin, Ping Yuan, Meng Yang, Jianbo Gao","doi":"10.1111/1759-7714.15331","DOIUrl":"https://doi.org/10.1111/1759-7714.15331","url":null,"abstract":"BACKGROUND\u0000The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs).\u0000\u0000\u0000METHODS\u0000This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed.\u0000\u0000\u0000RESULTS\u0000The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001).\u0000\u0000\u0000CONCLUSION\u0000HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline 18F-FDG PET/CT might be promising to identify patients with poor prognosis.","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140970912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne With Mikkelsen, Anna Christine Nilsson, Helene Broch Tenstad, Soeren Thue Lillevang, Nasrin Asgari
IntroductionSmall‐cell lung cancer (SCLC) may be associated with neuronal autoantibodies and paraneoplastic neurological syndromes. It has been suggested that neuronal autoantibodies, especially antineuronal nuclear antibody type 1 (Hu) autoantibodies, are associated with longer survival of patients with SCLC. The objective of this study was to determine the frequency and distribution of neuronal autoantibodies at the time of diagnosis of SCLC patients and assess survival rates in relation to autoimmunity.MethodsIn this retrospective study, serum from 40 patients with biopsy‐proven SCLC at the time of diagnosis was studied prior to treatment. The sera originated from a cancer registry at the Oncology Department, Vejle Hospital from 2007 to 2010. The sera were analyzed blindly to clinical status for the presence of neuronal autoantibodies. Medical records were reviewed for neurological symptoms.ResultsNeuronal autoantibodies were detected in 22/40 (55%) of the SCLC patients. A broad range of neurological symptoms was recorded in 28/40 (70%) patients, of which 14/28 (50%) were positive for neuronal autoantibodies. The most frequently detected autoantibodies were Hu (7/40, 17.5%) followed by GAD65 (6/22, 15.0%). Striational and P/Q‐ or N‐type voltage‐gated calcium channel antibodies were less common, with each found in five patients (12.5%). Eight patients (20%) had coexisting autoantibodies. Autoantibody‐positivity was not associated with survival.ConclusionNeuronal autoantibodies were at time of diagnosis found in approximately half of the treatment‐naïve SCLC patients. Neither autoantibody positivity at diagnosis nor neurological manifestations correlated with survival and their clinical importance requires further studies in larger, prospective cohorts.
{"title":"Initial screening for neuronal autoantibodies and their putative impact on survival in patients with small‐cell lung cancer","authors":"Anne With Mikkelsen, Anna Christine Nilsson, Helene Broch Tenstad, Soeren Thue Lillevang, Nasrin Asgari","doi":"10.1111/1759-7714.15318","DOIUrl":"https://doi.org/10.1111/1759-7714.15318","url":null,"abstract":"IntroductionSmall‐cell lung cancer (SCLC) may be associated with neuronal autoantibodies and paraneoplastic neurological syndromes. It has been suggested that neuronal autoantibodies, especially antineuronal nuclear antibody type 1 (Hu) autoantibodies, are associated with longer survival of patients with SCLC. The objective of this study was to determine the frequency and distribution of neuronal autoantibodies at the time of diagnosis of SCLC patients and assess survival rates in relation to autoimmunity.MethodsIn this retrospective study, serum from 40 patients with biopsy‐proven SCLC at the time of diagnosis was studied prior to treatment. The sera originated from a cancer registry at the Oncology Department, Vejle Hospital from 2007 to 2010. The sera were analyzed blindly to clinical status for the presence of neuronal autoantibodies. Medical records were reviewed for neurological symptoms.ResultsNeuronal autoantibodies were detected in 22/40 (55%) of the SCLC patients. A broad range of neurological symptoms was recorded in 28/40 (70%) patients, of which 14/28 (50%) were positive for neuronal autoantibodies. The most frequently detected autoantibodies were Hu (7/40, 17.5%) followed by GAD65 (6/22, 15.0%). Striational and P/Q‐ or N‐type voltage‐gated calcium channel antibodies were less common, with each found in five patients (12.5%). Eight patients (20%) had coexisting autoantibodies. Autoantibody‐positivity was not associated with survival.ConclusionNeuronal autoantibodies were at time of diagnosis found in approximately half of the treatment‐naïve SCLC patients. Neither autoantibody positivity at diagnosis nor neurological manifestations correlated with survival and their clinical importance requires further studies in larger, prospective cohorts.","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BackgroundAtezolizumab, one of the immune checkpoint inhibitors, has been approved as an adjuvant treatment following resection and platinum‐based chemotherapy in patients with stage II–IIIA non‐small cell lung cancer with 1% or more programmed death ligand‐1 (PD‐L1) expression. The Food and Drug Administration (FDA) has approved SP263 as a companion diagnostic assay for adjuvant treatment with atezolizumab; however, in clinical practice, the 22C3 assay is most commonly used for advanced non‐small cell lung cancer. Therefore, our study aimed to compare two PD‐L1 assays, SP263 and 22C3, to evaluate whether 22C3 could replace SP263 when deciding whether to administer adjuvant atezolizumab.MethodsWe retrospectively and prospectively analyzed 98 patients who underwent surgical resection at Kanagawa Cancer Center (Japan). An immunohistochemistry assay was performed for all the cases with both SP263 and 22C3. We statistically analyzed the concordance of PD‐L1 expression between SP263 and 22C3 assays.ResultsThe concordance between the two assays using Cohen's kappa was κ = 0.670 (95% CI: 0.522–0.818) at the 1% cutoff and κ = 0.796 (95% CI: 0.639–0.954) at the 50% cutoff. The Spearman correlation coefficient of 0.874 (p < 0.01) indicated high concordance. PD‐L1 expression with 22C3 resulted slightly higher than that with SP263.ConclusionsThis study showed a high concordance of PD‐L1 expression with the SP263 and 22C3 assays. Further studies examining the therapeutic effects of adjuvant atezolizumab are required.
{"title":"Comparison of SP263 and 22C3 pharmDx assays to test programmed death ligand‐1 (PD‐L1) expression in surgically resected non‐small cell lung cancer","authors":"Naoko Shigeta, Shuji Murakami, Tomoyuki Yokose, Tetsuya Isaka, Kanako Shinada, Takuya Nagashima, Hiroyuki Adachi, Shunsuke Shigefuku, Kotaro Murakami, Jun Miura, Noritake Kikunishi, Kozue Watabe, Haruhiro Saito, Hiroyuki Ito","doi":"10.1111/1759-7714.15319","DOIUrl":"https://doi.org/10.1111/1759-7714.15319","url":null,"abstract":"BackgroundAtezolizumab, one of the immune checkpoint inhibitors, has been approved as an adjuvant treatment following resection and platinum‐based chemotherapy in patients with stage II–IIIA non‐small cell lung cancer with 1% or more programmed death ligand‐1 (PD‐L1) expression. The Food and Drug Administration (FDA) has approved SP263 as a companion diagnostic assay for adjuvant treatment with atezolizumab; however, in clinical practice, the 22C3 assay is most commonly used for advanced non‐small cell lung cancer. Therefore, our study aimed to compare two PD‐L1 assays, SP263 and 22C3, to evaluate whether 22C3 could replace SP263 when deciding whether to administer adjuvant atezolizumab.MethodsWe retrospectively and prospectively analyzed 98 patients who underwent surgical resection at Kanagawa Cancer Center (Japan). An immunohistochemistry assay was performed for all the cases with both SP263 and 22C3. We statistically analyzed the concordance of PD‐L1 expression between SP263 and 22C3 assays.ResultsThe concordance between the two assays using Cohen's kappa was <jats:italic>κ</jats:italic> = 0.670 (95% CI: 0.522–0.818) at the 1% cutoff and <jats:italic>κ</jats:italic> = 0.796 (95% CI: 0.639–0.954) at the 50% cutoff. The Spearman correlation coefficient of 0.874 (<jats:italic>p</jats:italic> < 0.01) indicated high concordance. PD‐L1 expression with 22C3 resulted slightly higher than that with SP263.ConclusionsThis study showed a high concordance of PD‐L1 expression with the SP263 and 22C3 assays. Further studies examining the therapeutic effects of adjuvant atezolizumab are required.","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well‐established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89‐year‐old female, diagnosed with epidermal growth factor receptor (EGFR)‐mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis.
{"title":"Concomitant osimertinib and antituberculosis therapy in an elderly patient with EGFR‐mutated lung cancer and pulmonary tuberculosis: A case report","authors":"Hiroaki Matsuura, Hisao Higo, Tadahiro Kuribayashi, Akihiko Tamaoki, Takamasa Nakasuka, Mari Uno, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Nobuaki Miyahara, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Kadoaki Ohashi","doi":"10.1111/1759-7714.15324","DOIUrl":"https://doi.org/10.1111/1759-7714.15324","url":null,"abstract":"The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well‐established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89‐year‐old female, diagnosed with epidermal growth factor receptor (<jats:italic>EGFR</jats:italic>)‐mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis.","PeriodicalId":23338,"journal":{"name":"Thoracic Cancer","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}