Pub Date : 2024-12-01Epub Date: 2024-06-10DOI: 10.1007/s12094-024-03523-3
Jaime Espinós, José Manuel Aramendía, Antonio González-Martín, Marta Santisteban, Luisa Sánchez, Ángel Vizcay, José Ángel Mínguez, Juan Luis Alcázar
Objective: Various systemic inflammation response indexes (SIRI) have repeatedly been described as prognostic factors in ovarian cancer. They have not been validated in prospective trials and published results are sometimes contradictory. We aimed to explore their role in a cohort of patients diagnosed with stage III and IV ovarian cancer treated at our institution.
Methods: We retrospectively examined the prognostic influence of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), the red cell distribution width (RDW), and the mean platelet volume (MPV).
Results: A total of 77 patients were analyzed. NLR > 2.243 at diagnosis, NLR before primary surgery, MLR at diagnosis, PLR > 289.1 at diagnosis, and PLR at diagnosis were significant in univariate Cox regression for progression-free survival, but none of them retained their significance in the multivariate Cox regression analysis. For overall survival, NLR > = 2.53 at diagnosis, MLR > = 0.245 at diagnosis, and PLR > = 198.3 at diagnosis resulted significant in univariate COX regression; only PLR > = 198.3 at diagnosis retained its significance in the multivariate analysis.
Conclusion: In our cohort, PLR > = 198.3 was an independent prognostic factor for worse OS. The definitive role of SIRI in ovarian cancer has not yet been established. If their value as prognostic factors could finally be established, they would become a simple and economical method to predict prognosis in patients with advanced ovarian cancer. Therefore, it is time to conduct prospective, multicenter studies with larger samples to definitively establish its role in ovarian cancer, if any.
{"title":"Prognostic value of systemic inflammation response indexes obtained from the complete blood count in patients treated for advanced ovarian carcinoma in front line.","authors":"Jaime Espinós, José Manuel Aramendía, Antonio González-Martín, Marta Santisteban, Luisa Sánchez, Ángel Vizcay, José Ángel Mínguez, Juan Luis Alcázar","doi":"10.1007/s12094-024-03523-3","DOIUrl":"10.1007/s12094-024-03523-3","url":null,"abstract":"<p><strong>Objective: </strong>Various systemic inflammation response indexes (SIRI) have repeatedly been described as prognostic factors in ovarian cancer. They have not been validated in prospective trials and published results are sometimes contradictory. We aimed to explore their role in a cohort of patients diagnosed with stage III and IV ovarian cancer treated at our institution.</p><p><strong>Methods: </strong>We retrospectively examined the prognostic influence of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), the red cell distribution width (RDW), and the mean platelet volume (MPV).</p><p><strong>Results: </strong>A total of 77 patients were analyzed. NLR > 2.243 at diagnosis, NLR before primary surgery, MLR at diagnosis, PLR > 289.1 at diagnosis, and PLR at diagnosis were significant in univariate Cox regression for progression-free survival, but none of them retained their significance in the multivariate Cox regression analysis. For overall survival, NLR > = 2.53 at diagnosis, MLR > = 0.245 at diagnosis, and PLR > = 198.3 at diagnosis resulted significant in univariate COX regression; only PLR > = 198.3 at diagnosis retained its significance in the multivariate analysis.</p><p><strong>Conclusion: </strong>In our cohort, PLR > = 198.3 was an independent prognostic factor for worse OS. The definitive role of SIRI in ovarian cancer has not yet been established. If their value as prognostic factors could finally be established, they would become a simple and economical method to predict prognosis in patients with advanced ovarian cancer. Therefore, it is time to conduct prospective, multicenter studies with larger samples to definitively establish its role in ovarian cancer, if any.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3211-3217"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297169","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: Breast cancer (BRCA) is one of the most common malignant tumors. The structural maintenance of chromosome (SMC) gene family has been shown to play an important role in human cancers. However, the role of SMC families in BRCA is unclear. This study aimed to explore the role and potential clinical value of whole SMCs in BRCA.
Methods: TIMER and UALCAN database were used to analysis the expression level. Genetic variations were analyzed by cBioPortal. Promoter methylation and protein level were analyzed by UCLCAN. GO and KEGG were analyzed by Metascape database. Prognostic value of SMCs was analyzed by Kaplan-Meier and multivariate cox regression analyses. Immune infiltration analysis was conducted by CIBERSORT. Immunotherapy outcome prediction was conducted by Cancer Immunome Atlas. Targeted drug therapy outcome prediction was taken by GDSC and R language. The cell viability was tested by CCK8 and migration was tested by wound healing assay. Xenograft model was used to investigate the in vivo role of SMC2.
Results: Expression levels of SMC1A, SMC2, SMC4, SMC5 and SMC6 mRNA were increased in BRCA tissues, and negatively correlated with promoter methylation. Overexpression of SMC2 and SMC4 was negatively correlated with survival. Function of SMCs family regulatory genes was mainly related to ATPase activity. Expression of most SMCs was negatively correlated with immunotherapy and drug therapy outcomes. Interfere SMC2 and SMC4 decreased IC50 values of 5-fluorouracil and oxaliplatin and inhibited the migration of MCF7 cells. Tumor growth and weights were significantly decreased in si-SMC2 groups.
Conclusions: Combined bioinformatics and clinical specimen analysis verified SMC2 and SMC4 as independent prognostic factors in BRCA, suggesting their significance for the diagnosis and treatment of BRCA.
{"title":"Identification of SMC2 and SMC4 as prognostic markers in breast cancer through bioinformatics analysis.","authors":"Lili Pei, Yu Li, Hao Gu, Siqi Wang, Wenhao Wu, Siyi Fan, Xiao Shi, Xinxin Si","doi":"10.1007/s12094-024-03521-5","DOIUrl":"10.1007/s12094-024-03521-5","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BRCA) is one of the most common malignant tumors. The structural maintenance of chromosome (SMC) gene family has been shown to play an important role in human cancers. However, the role of SMC families in BRCA is unclear. This study aimed to explore the role and potential clinical value of whole SMCs in BRCA.</p><p><strong>Methods: </strong>TIMER and UALCAN database were used to analysis the expression level. Genetic variations were analyzed by cBioPortal. Promoter methylation and protein level were analyzed by UCLCAN. GO and KEGG were analyzed by Metascape database. Prognostic value of SMCs was analyzed by Kaplan-Meier and multivariate cox regression analyses. Immune infiltration analysis was conducted by CIBERSORT. Immunotherapy outcome prediction was conducted by Cancer Immunome Atlas. Targeted drug therapy outcome prediction was taken by GDSC and R language. The cell viability was tested by CCK8 and migration was tested by wound healing assay. Xenograft model was used to investigate the in vivo role of SMC2.</p><p><strong>Results: </strong>Expression levels of SMC1A, SMC2, SMC4, SMC5 and SMC6 mRNA were increased in BRCA tissues, and negatively correlated with promoter methylation. Overexpression of SMC2 and SMC4 was negatively correlated with survival. Function of SMCs family regulatory genes was mainly related to ATPase activity. Expression of most SMCs was negatively correlated with immunotherapy and drug therapy outcomes. Interfere SMC2 and SMC4 decreased IC<sub>50</sub> values of 5-fluorouracil and oxaliplatin and inhibited the migration of MCF7 cells. Tumor growth and weights were significantly decreased in si-SMC2 groups.</p><p><strong>Conclusions: </strong>Combined bioinformatics and clinical specimen analysis verified SMC2 and SMC4 as independent prognostic factors in BRCA, suggesting their significance for the diagnosis and treatment of BRCA.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2952-2965"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077254","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}
Pub Date : 2024-12-01Epub Date: 2024-05-30DOI: 10.1007/s12094-024-03475-8
Meiying Jiang, Qiyun Yu, Haitao Mei, Yingchao Jian, Rong Xu
Objective: This research was aimed at investigating the early diagnostic value of emission computed tomograph (ECT) whole-body bone imaging combined with PINP and β-CTX for bone metastasis of lung cancer.
Methods: Case data of 86 lung cancer patients were categorized into lung cancer with bone metastasis (LCWBM, 46 cases) and lung cancer without bone metastasis (LCWOBM, 40 cases) groups according to the presence or absence of bone metastasis. Patients' general information were collected. ECT whole-body bone imaging was used to detect bone metastases and the grading of the extent of disease (EOD) in both groups, and electrochemiluminescence was utilized to detect the serum levels of PINP and β-CTX. Spearman correlation analysis was employed to evaluate the correlation between EOD grading and PINP and β-CTX levels. Logistic univariate and multivariate regression was implemented to analyze the risk factors of bone metastasis of lung cancer. Receiver operating characteristic (ROC) curve was applied to analyze the diagnostic efficacy of the single test of ECT whole-body bone imaging, PINP, or β-CTX and the combination of the three tests.
Results: The differences in pathological type, clinical stage and EOD grading, the number of positive ECT cases, and the expression levels of PINP and β-CTX between the LCWBM and LCWOBM groups were statistically significant. In LCWBM patients with different EOD grading, the trends of the expression of PINP and β-CTX were grade 3 > grade 2 > grade 1 and grade 0. Further correlation analyses revealed that EOD grading showed a significant positive correlation with the PINP and β-CTX expression levels. Univariate logistic regression analysis demonstrated that adenocarcinoma, TNM stage IV, ECT positivity, and high expression of PINP and β-CTX were associated with bone metastasis of lung cancer, and multivariate logistic regression analysis indicated that ECT positivity, high expression of PINP and β-CTX were independent risk factors for bone metastasis of lung cancer. The area under the curve (AUC) of ECT, PINP, and β-CTX alone for the diagnosis of bone metastasis of lung cancer were 0.872, 0.888, and 0.874, respectively, and the AUC for the combined diagnosis of the three was 0.963, which was greater than that of any one of the individual indices, with a sensitivity of 86.96% and a specificity of 97.50% at a Youden index of 0.845.
Conclusion: ECT whole-body bone imaging combined with PINP and β-CTX has high diagnostic value for bone metastasis of lung cancer.
{"title":"Early diagnostic value of ECT whole-body bone imaging combined with PINP and β-CTX for bone metastasis of lung cancer.","authors":"Meiying Jiang, Qiyun Yu, Haitao Mei, Yingchao Jian, Rong Xu","doi":"10.1007/s12094-024-03475-8","DOIUrl":"10.1007/s12094-024-03475-8","url":null,"abstract":"<p><strong>Objective: </strong>This research was aimed at investigating the early diagnostic value of emission computed tomograph (ECT) whole-body bone imaging combined with PINP and β-CTX for bone metastasis of lung cancer.</p><p><strong>Methods: </strong>Case data of 86 lung cancer patients were categorized into lung cancer with bone metastasis (LCWBM, 46 cases) and lung cancer without bone metastasis (LCWOBM, 40 cases) groups according to the presence or absence of bone metastasis. Patients' general information were collected. ECT whole-body bone imaging was used to detect bone metastases and the grading of the extent of disease (EOD) in both groups, and electrochemiluminescence was utilized to detect the serum levels of PINP and β-CTX. Spearman correlation analysis was employed to evaluate the correlation between EOD grading and PINP and β-CTX levels. Logistic univariate and multivariate regression was implemented to analyze the risk factors of bone metastasis of lung cancer. Receiver operating characteristic (ROC) curve was applied to analyze the diagnostic efficacy of the single test of ECT whole-body bone imaging, PINP, or β-CTX and the combination of the three tests.</p><p><strong>Results: </strong>The differences in pathological type, clinical stage and EOD grading, the number of positive ECT cases, and the expression levels of PINP and β-CTX between the LCWBM and LCWOBM groups were statistically significant. In LCWBM patients with different EOD grading, the trends of the expression of PINP and β-CTX were grade 3 > grade 2 > grade 1 and grade 0. Further correlation analyses revealed that EOD grading showed a significant positive correlation with the PINP and β-CTX expression levels. Univariate logistic regression analysis demonstrated that adenocarcinoma, TNM stage IV, ECT positivity, and high expression of PINP and β-CTX were associated with bone metastasis of lung cancer, and multivariate logistic regression analysis indicated that ECT positivity, high expression of PINP and β-CTX were independent risk factors for bone metastasis of lung cancer. The area under the curve (AUC) of ECT, PINP, and β-CTX alone for the diagnosis of bone metastasis of lung cancer were 0.872, 0.888, and 0.874, respectively, and the AUC for the combined diagnosis of the three was 0.963, which was greater than that of any one of the individual indices, with a sensitivity of 86.96% and a specificity of 97.50% at a Youden index of 0.845.</p><p><strong>Conclusion: </strong>ECT whole-body bone imaging combined with PINP and β-CTX has high diagnostic value for bone metastasis of lung cancer.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3116-3123"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176825","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}
Purpose: Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date.
Methods: Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan-Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model.
Results: We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74%) and DFS (87.65 vs. 90.96%) between stage III patients with pT1-3N + (P-LNR ≤ 0.15)M0 and those with pT1-3N0M0. Further analysis demonstrated that CRC patients with pT1-3N + (P-LNR ≤ 0.15)M0 were less likely to benefit from 8 cycles of CAPOX or FOLFOX chemotherapy and suffered fewer adverse events from declining chemotherapy. Comparing with 0-4 cycles versus 8 cycles, the overall survival rates were 91.35 versus 90.19% (P = 0.79), and with a DFS of 87.50 versus 88.24% (P = 0.49), the duration of adjuvant chemotherapy was not an independent risk factor for patients with pT1-3N + (P-LNR ≤ 0.15)M0 (HR: 0.70, 95% CI 0.90-1.30, P = 0.42).
Conclusion: The concept of P-LNR we proposed might have a high clinical application value and accurately enable clinicians to screen out specific CRC patients who decline or prefer limited chemotherapy.
Trial registry: The clinical trial registration number: ChiCTR2300076883.
目的:多项研究发现,一些 III 期结直肠癌(CRC)患者无法从标准辅助化疗中获益。然而,迄今为止还没有统一的筛查标准:纳入2016年1月至2018年12月期间在3个中心接受治疗的病理确诊结肠腺癌患者。根据不同分期和阳性旁淋巴结比(P-LNR)将患者分为四组[队列1:pT1-3N0M0,队列2:pT1-3N+(P-LNR≤0.15)M0,队列3:pT4N0M0,队列4:除pT1-3N+(P-LNR≤0.15)M0外的III期患者],并采用Kaplan-Meier法进一步比较总生存期。采用cox比例危险度模型进行单变量和多变量分析:我们对 5581 例连续的 CRC 患者进行了回顾性分析,并对 2861 例符合条件的患者进行了进一步分析。在我们的研究中,P-LNR的最佳临界值为0.15。pT1-3N+(P-LNR≤0.15)M0的III期患者与pT1-3N0M0的患者在OS(91.36% vs. 93.74%)和DFS(87.65% vs. 90.96%)方面无明显差异。进一步分析表明,pT1-3N +(P-LNR ≤ 0.15)M0 的 CRC 患者从 8 个周期的 CAPOX 或 FOLFOX 化疗中获益的可能性较小,且因拒绝化疗而发生的不良事件较少。0-4个周期与8个周期相比,总生存率为91.35%对90.19%(P=0.79),DFS为87.50%对88.24%(P=0.49),辅助化疗持续时间不是pT1-3N+(P-LNR≤0.15)M0患者的独立危险因素(HR:0.70,95% CI 0.90-1.30,P=0.42):结论:我们提出的P-LNR概念可能具有较高的临床应用价值,可使临床医生准确筛选出拒绝或倾向于有限化疗的特定CRC患者:临床试验注册号:ChiCTR2300076883ChiCTR2300076883。
{"title":"Survival analysis in pT1-3 and paracolic lymph-node invasion colorectal cancer: the prognostic role of positive paracolic lymph-node ratio for adjuvant chemotherapy.","authors":"Xiaochuang Feng, Weilin Liao, Yuqing Tang, Xiaojiang Yi, Tieqiao Tian, Hongming Li, Jiaxin Lin, Xinquan Lu, Jin Wan, Jiahao Wang, Haijun Deng, Chuangqi Chen, Dechang Diao","doi":"10.1007/s12094-024-03470-z","DOIUrl":"10.1007/s12094-024-03470-z","url":null,"abstract":"<p><strong>Purpose: </strong>Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date.</p><p><strong>Methods: </strong>Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan-Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model.</p><p><strong>Results: </strong>We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74%) and DFS (87.65 vs. 90.96%) between stage III patients with pT1-3N + (P-LNR ≤ 0.15)M0 and those with pT1-3N0M0. Further analysis demonstrated that CRC patients with pT1-3N + (P-LNR ≤ 0.15)M0 were less likely to benefit from 8 cycles of CAPOX or FOLFOX chemotherapy and suffered fewer adverse events from declining chemotherapy. Comparing with 0-4 cycles versus 8 cycles, the overall survival rates were 91.35 versus 90.19% (P = 0.79), and with a DFS of 87.50 versus 88.24% (P = 0.49), the duration of adjuvant chemotherapy was not an independent risk factor for patients with pT1-3N + (P-LNR ≤ 0.15)M0 (HR: 0.70, 95% CI 0.90-1.30, P = 0.42).</p><p><strong>Conclusion: </strong>The concept of P-LNR we proposed might have a high clinical application value and accurately enable clinicians to screen out specific CRC patients who decline or prefer limited chemotherapy.</p><p><strong>Trial registry: </strong>The clinical trial registration number: ChiCTR2300076883.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2993-3002"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089308","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}
Background: The aim of this study is to explore the prognostic value and immune signature of ITGB4 expression in lung adenocarcinoma (LUAD) brain metastasis.
Methods: We comprehensively screened genes associated with LUAD brain metastasis by integrating datasets from the GEO database and TMT-based quantitative proteomics profiles. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival, and a risk model was constructed. The biological functions were explored via GO and KEGG analysis. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. In addition, we use TIMER to explore the collection of ITGB4 Expression and Immune Infiltration Level in LUAD. The ability of ITGB4 to regulate tumor metastasis was further assessed by migration, invasion assay and Western-blot in H1975-BrM4 cells.
Results: We found that ITGB4 was the only gene with high clinical diagnostic and prognostic value in LUAD. Enrichment analysis indicated that ITGB4 is associated with brain metastasis, infiltration of immune cells, and the response to immunotherapy. ITGB4 expression can effectively predict the outcomes of patients with LUAD who are receiving anti-PD-1 therapy. ITGB4 knockdown inhibited the invasion, migration of H1975-BrM4 brain metastasis cells, as well as epithelial-mesenchymal transition (EMT) abilities. The heightened expression of ITGB4 protein was shown to promote EMT and enhance the metastatic potential. ITGB4 promotes the progression in H1975-BrM4 cells via MEK/ERK signaling pathway.
Conclusions: Our findings indicate that the expression of ITGB4 is linked to the occurrence of brain metastasis and infiltration of immune cells, suggesting that ITGB4 might be a clinical treatment target for LUAD.
{"title":"ITGB4 is a prognostic biomarker and correlated with lung adenocarcinoma brain metastasis.","authors":"Jingjing Zhang, Lingjie Li, Weiwei Luo, Shenglin Ma, Yanyan Zhao","doi":"10.1007/s12094-024-03527-z","DOIUrl":"10.1007/s12094-024-03527-z","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study is to explore the prognostic value and immune signature of ITGB4 expression in lung adenocarcinoma (LUAD) brain metastasis.</p><p><strong>Methods: </strong>We comprehensively screened genes associated with LUAD brain metastasis by integrating datasets from the GEO database and TMT-based quantitative proteomics profiles. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival, and a risk model was constructed. The biological functions were explored via GO and KEGG analysis. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. In addition, we use TIMER to explore the collection of ITGB4 Expression and Immune Infiltration Level in LUAD. The ability of ITGB4 to regulate tumor metastasis was further assessed by migration, invasion assay and Western-blot in H1975-BrM4 cells.</p><p><strong>Results: </strong>We found that ITGB4 was the only gene with high clinical diagnostic and prognostic value in LUAD. Enrichment analysis indicated that ITGB4 is associated with brain metastasis, infiltration of immune cells, and the response to immunotherapy. ITGB4 expression can effectively predict the outcomes of patients with LUAD who are receiving anti-PD-1 therapy. ITGB4 knockdown inhibited the invasion, migration of H1975-BrM4 brain metastasis cells, as well as epithelial-mesenchymal transition (EMT) abilities. The heightened expression of ITGB4 protein was shown to promote EMT and enhance the metastatic potential. ITGB4 promotes the progression in H1975-BrM4 cells via MEK/ERK signaling pathway.</p><p><strong>Conclusions: </strong>Our findings indicate that the expression of ITGB4 is linked to the occurrence of brain metastasis and infiltration of immune cells, suggesting that ITGB4 might be a clinical treatment target for LUAD.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2979-2992"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077255","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}
Introduction: Prostate cancer is a common urology malignant in males, ranking second globally. The disease is especially severe when diagnosed alongside hypertension. MKI67 is an established marker of neoplastic cell proliferation in humans, but the significance of its prognostic value in patients with prostate cancer and hypertension requires further research.
Methods: In this retrospective analysis, we evaluated 296 hypertensive prostate cancer patients between March 2, 2012, and November 1, 2015. We used Cox regression models and prediction analysis to assess overall survival. Furthermore, we created a nomogram and verified its accuracy using a calibration curve.
Results: Of all participants, 101 (34.12%) died. Our multi-factor analysis revealed that MKI67 expression was associated with an increased hazard ratio of death (> fivefold) (Hazard Ratio 5.829, 95% CI 3.349-10.138, p value < 0.01) and progression (twofold) (HR 2.059, 95% CI 1.368-3.102, p value < 0.01). Our Lasso analysis model displayed that several factors, including heart failure, smoking, ACS, serum albumin, Gealson score, prognostic nutritional index, MKI67 expression, surgery, and stage were high risks of prostate cancer. To ensure each covariate's contribution to cancer prognosis, we created a Cox model nomogram, which accurately predicted the risk of death (C-statistic of 0.8289) and had a proper calibration plot for risk assessment.
Conclusion: MKI67 expression predicts poor outcomes for overall mortality in prostate cancer and hypertension patients. Additionally, our cross-validated multivariate score, which includes MKI67, demonstrated accuracy efficacy of predicting prognosis.
{"title":"MKI67 with arterial hypertension predict a poor survival for prostate cancer patients, a real-life investigation.","authors":"Yongqiang Zhou, Weihai Chen, Hao Jiang, Yuke Zhang, Zheng Ma, Zhenfan Wang, Chen Xu, Minjun Jiang, Jianchun Chen, Zhijun Cao","doi":"10.1007/s12094-024-03505-5","DOIUrl":"10.1007/s12094-024-03505-5","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer is a common urology malignant in males, ranking second globally. The disease is especially severe when diagnosed alongside hypertension. MKI67 is an established marker of neoplastic cell proliferation in humans, but the significance of its prognostic value in patients with prostate cancer and hypertension requires further research.</p><p><strong>Methods: </strong>In this retrospective analysis, we evaluated 296 hypertensive prostate cancer patients between March 2, 2012, and November 1, 2015. We used Cox regression models and prediction analysis to assess overall survival. Furthermore, we created a nomogram and verified its accuracy using a calibration curve.</p><p><strong>Results: </strong>Of all participants, 101 (34.12%) died. Our multi-factor analysis revealed that MKI67 expression was associated with an increased hazard ratio of death (> fivefold) (Hazard Ratio 5.829, 95% CI 3.349-10.138, p value < 0.01) and progression (twofold) (HR 2.059, 95% CI 1.368-3.102, p value < 0.01). Our Lasso analysis model displayed that several factors, including heart failure, smoking, ACS, serum albumin, Gealson score, prognostic nutritional index, MKI67 expression, surgery, and stage were high risks of prostate cancer. To ensure each covariate's contribution to cancer prognosis, we created a Cox model nomogram, which accurately predicted the risk of death (C-statistic of 0.8289) and had a proper calibration plot for risk assessment.</p><p><strong>Conclusion: </strong>MKI67 expression predicts poor outcomes for overall mortality in prostate cancer and hypertension patients. Additionally, our cross-validated multivariate score, which includes MKI67, demonstrated accuracy efficacy of predicting prognosis.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3037-3049"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094409","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}
Pub Date : 2024-12-01Epub Date: 2024-06-12DOI: 10.1007/s12094-024-03561-x
Fengchao Liu, Susu Ye, Liu Zhao, Qinghui Niu
Cancer stem cells (CSCs) are a group of tumor cells with high tumorigenic ability and self-renewal potential similar to those of normal stem cells. CSCs are the key "seeds" for tumor development, metastasis, and recurrence. A better insight into the key mechanisms underlying CSC survival improves the efficiency of cancer therapy via specific targeting of CSCs. Insulin-like growth factor (IGF)/IGF-1 receptor (IGF-1R) signaling plays an important role in the maintenance of cancer stemness. However, the effect of IGF/IGF-1R signaling on stemness and CSCs and the underlying mechanisms are still controversial. Based on the similarity between CSCs and normal stem cells, this review discusses emerging data on the functions of IGF/IGF-1R signaling in normal stem cells and CSCs and dissects the underlying mechanisms by which IGF/IGF-1R signaling is involved in CSCs. On the other hand, this review highlighted the role of IGF/IGF-1R signaling blockade in multiple CSCs as a potential strategy to improve CSC-based therapy.
{"title":"The role of IGF/IGF-1R signaling in the regulation of cancer stem cells.","authors":"Fengchao Liu, Susu Ye, Liu Zhao, Qinghui Niu","doi":"10.1007/s12094-024-03561-x","DOIUrl":"10.1007/s12094-024-03561-x","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a group of tumor cells with high tumorigenic ability and self-renewal potential similar to those of normal stem cells. CSCs are the key \"seeds\" for tumor development, metastasis, and recurrence. A better insight into the key mechanisms underlying CSC survival improves the efficiency of cancer therapy via specific targeting of CSCs. Insulin-like growth factor (IGF)/IGF-1 receptor (IGF-1R) signaling plays an important role in the maintenance of cancer stemness. However, the effect of IGF/IGF-1R signaling on stemness and CSCs and the underlying mechanisms are still controversial. Based on the similarity between CSCs and normal stem cells, this review discusses emerging data on the functions of IGF/IGF-1R signaling in normal stem cells and CSCs and dissects the underlying mechanisms by which IGF/IGF-1R signaling is involved in CSCs. On the other hand, this review highlighted the role of IGF/IGF-1R signaling blockade in multiple CSCs as a potential strategy to improve CSC-based therapy.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2924-2934"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307260","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}
Pub Date : 2024-12-01Epub Date: 2024-05-25DOI: 10.1007/s12094-024-03507-3
Xusheng Tang, Xiaojuan Hu, Lin Yuan, Hainan Yang, Yunfen Luo, Da Liu, Qingjun Hu, Changguo Shan, Tao Lin, Linbo Cai, Zhaoming Zhou, Xin Jin, Ming Lei, Weiping Hong
Background: To assess the genetic characteristics of central nervous system (CNS) metastases from non-small-cell lung cancer (NSCLC), we gathered the genetic profiles of brain metastases (BM) and leptomeningeal metastases (LM). Our objective was to identify genetic factors contributing to poorer overall survival (OS) in NSCLC patients with LM.
Methods: This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing.
Results: Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044).
Conclusions: Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.
{"title":"Different genetic profiles contribute to worse overall survival in patients with leptomeningeal metastases of non-small-cell lung cancer.","authors":"Xusheng Tang, Xiaojuan Hu, Lin Yuan, Hainan Yang, Yunfen Luo, Da Liu, Qingjun Hu, Changguo Shan, Tao Lin, Linbo Cai, Zhaoming Zhou, Xin Jin, Ming Lei, Weiping Hong","doi":"10.1007/s12094-024-03507-3","DOIUrl":"10.1007/s12094-024-03507-3","url":null,"abstract":"<p><strong>Background: </strong>To assess the genetic characteristics of central nervous system (CNS) metastases from non-small-cell lung cancer (NSCLC), we gathered the genetic profiles of brain metastases (BM) and leptomeningeal metastases (LM). Our objective was to identify genetic factors contributing to poorer overall survival (OS) in NSCLC patients with LM.</p><p><strong>Methods: </strong>This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing.</p><p><strong>Results: </strong>Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044).</p><p><strong>Conclusions: </strong>Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3058-3064"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097250","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}
Pub Date : 2024-12-01Epub Date: 2024-06-11DOI: 10.1007/s12094-024-03511-7
Enric Carcereny, Delvys Rodriguez-Abreu, Rafael Lopez, Fabio Franco, Maria Guirado, Bartomeu Massutí, Manuel Cobo, Ana Blasco, Guillermo Suay, Edel Del Barco, Ana Laura Ortega, Maria Angeles Sala, Patricia Cordeiro, Reyes Bernabé, José Luís González Larriba, Joaquim Bosch-Barrera, Julia Calzas, Joaquín Casal, Airam Padilla, Alfredo Sánchez-Hernandez, Mariano Provencio
Background: Non-small cell lung cancer (NSCLC) accounts for the vast majority of all diagnosed lung cancers. According to their histology, most NSCLCs are considered non-squamous cell carcinoma (NSCC), and up to 85% of the latter may lack either one of the two main actionable oncogenic drivers (i.e., EGFR mutations and ALK rearrangements).
Objective: Our analysis aimed to describe the clinical and epidemiological characteristics of Spanish patients suffering from NSCC with no actionable oncogenic driver in daily clinical practice.
Design: A retrospective, cross-sectional, descriptive analysis.
Methods: We analyzed the records of all Spanish patients with advanced NSCC diagnosed between January 2011 and January 2020 and included in the Spanish Thoracic Tumor Registry database. We evaluated the presence of metastasis and molecular profiling at the time of diagnosis and treatments received. We also assessed overall survival (OS) and progression-free survival (PFS) according to first-line treatment.
Results: One thousand seven hundred ninety-seven Spanish patients with NSCC were included. They were mainly men (73.2%), smokers (current [44.4%] and former [44.4%]) and presented adenocarcinoma histology (97.6%). Most patients had at least one comorbidity (80.4%) and one metastatic site (96.8%), and a non-negligible number of those tested were PD-L1 positive (35.2%). Notably, the presence of liver metastasis indicated a shorter median OS and PFS than metastasis in other locations (p < 0.001). Chemotherapy was more often prescribed than immunotherapy as first-, second-, and third-line treatment in that period. In first-line, the OS rates were similar in patients receiving either regimen, but PFS rates significantly better in patients treated with immunotherapy (p = 0.026). Also, a high number of patients did not reach second- and third-line treatment, suggesting the failure of current early diagnostic measures and therapies.
Conclusions: This analysis of the most lethal tumor in Spain could highlight the strengths and the weaknesses of its clinical management and set the ground for further advances and research.
{"title":"Advanced non-squamous NSCLC with no actionable oncogenic driver in Spain: a cross-sectional descriptive analysis of data from the Thoracic Tumor Registry.","authors":"Enric Carcereny, Delvys Rodriguez-Abreu, Rafael Lopez, Fabio Franco, Maria Guirado, Bartomeu Massutí, Manuel Cobo, Ana Blasco, Guillermo Suay, Edel Del Barco, Ana Laura Ortega, Maria Angeles Sala, Patricia Cordeiro, Reyes Bernabé, José Luís González Larriba, Joaquim Bosch-Barrera, Julia Calzas, Joaquín Casal, Airam Padilla, Alfredo Sánchez-Hernandez, Mariano Provencio","doi":"10.1007/s12094-024-03511-7","DOIUrl":"10.1007/s12094-024-03511-7","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) accounts for the vast majority of all diagnosed lung cancers. According to their histology, most NSCLCs are considered non-squamous cell carcinoma (NSCC), and up to 85% of the latter may lack either one of the two main actionable oncogenic drivers (i.e., EGFR mutations and ALK rearrangements).</p><p><strong>Objective: </strong>Our analysis aimed to describe the clinical and epidemiological characteristics of Spanish patients suffering from NSCC with no actionable oncogenic driver in daily clinical practice.</p><p><strong>Design: </strong>A retrospective, cross-sectional, descriptive analysis.</p><p><strong>Methods: </strong>We analyzed the records of all Spanish patients with advanced NSCC diagnosed between January 2011 and January 2020 and included in the Spanish Thoracic Tumor Registry database. We evaluated the presence of metastasis and molecular profiling at the time of diagnosis and treatments received. We also assessed overall survival (OS) and progression-free survival (PFS) according to first-line treatment.</p><p><strong>Results: </strong>One thousand seven hundred ninety-seven Spanish patients with NSCC were included. They were mainly men (73.2%), smokers (current [44.4%] and former [44.4%]) and presented adenocarcinoma histology (97.6%). Most patients had at least one comorbidity (80.4%) and one metastatic site (96.8%), and a non-negligible number of those tested were PD-L1 positive (35.2%). Notably, the presence of liver metastasis indicated a shorter median OS and PFS than metastasis in other locations (p < 0.001). Chemotherapy was more often prescribed than immunotherapy as first-, second-, and third-line treatment in that period. In first-line, the OS rates were similar in patients receiving either regimen, but PFS rates significantly better in patients treated with immunotherapy (p = 0.026). Also, a high number of patients did not reach second- and third-line treatment, suggesting the failure of current early diagnostic measures and therapies.</p><p><strong>Conclusions: </strong>This analysis of the most lethal tumor in Spain could highlight the strengths and the weaknesses of its clinical management and set the ground for further advances and research.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3218-3225"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307259","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}
Pub Date : 2024-12-01Epub Date: 2024-05-25DOI: 10.1007/s12094-024-03482-9
Manyi Xu, Yanhua Wang, Keda Shao, Yue Hao, Zhengbo Song
Background: The efficacy of afatinib or pyrotinib has been demonstrated in HER2-positive advanced non-small cell lung cancer (NSCLC) patients; however, the efficacy of pyrotinib after afatinib progression has yet to be determined.
Method: Patients with HER2 mutated advanced lung adenocarcinoma administered afatinib or pyrotinib monotherapy were enrolled. Those who received pyrotinib after afatinib were further analyzed to determine the efficacy and safety of pyrotinib after progression on afatinib. Survival curves were plotted with the Kaplan-Meier method. A swimming plot was used to describe the specific treatments. Additionally, patient-derived tumor organoids (PDTOs) were established from HER2-amplified NSCLC patient samples to investigate the antitumor activity of pyrotinib in HER2-amplified tumor cells in vitro.
Results: A total of 99 patients were enrolled, 13 of whom were administered pyrotinib after progression on afatinib. No statistical difference in PFS of pyrotinib was observed between patients whether be treated after afatinib progression or not (6.7 months vs. 4.4 months, P = 0.817), thus indicating that progression on afatinib did not affect the efficacy of pyrotinib. Further analysis was conducted on the former patients, which comprising eight patients administered interval chemotherapy after progression on afatinib. Two patients achieved PR after pyrotinib treatment. No independent factors were found to influence the PFS of pyrotinib. PDTOs confirmed the anti-tumor activity of pyrotinib in NSCLC tumor cells with HER2 amplification.
Conclusions: Progression after prior afatinib treatment does not influence the efficacy of pyrotinib treatment. Pyrotinib may be a salvage option for patients with HER2 mutation who have experienced progression on afatinib.
背景:阿法替尼或吡罗替尼对HER2阳性晚期非小细胞肺癌(NSCLC)患者的疗效已得到证实;然而,阿法替尼治疗进展后吡罗替尼的疗效尚未确定:方法:研究人员招募了接受阿法替尼或派罗替尼单药治疗的HER2突变晚期肺腺癌患者。对阿法替尼治疗后接受吡罗替尼治疗的患者进行进一步分析,以确定阿法替尼治疗进展后吡罗替尼的疗效和安全性。采用 Kaplan-Meier 法绘制生存曲线。游泳图用于描述特定的治疗方法。此外,还从HER2扩增的NSCLC患者样本中建立了患者衍生肿瘤器官组织(PDTOs),以研究吡罗替尼在体外HER2扩增肿瘤细胞中的抗肿瘤活性:共有99名患者入组,其中13名患者在阿法替尼治疗进展后接受了吡罗替尼治疗。阿法替尼治疗进展与否的患者服用吡罗替尼的PFS无统计学差异(6.7个月 vs. 4.4个月,P = 0.817),这表明阿法替尼治疗进展不影响吡罗替尼的疗效。进一步的分析是针对阿法替尼治疗进展后接受间歇化疗的前患者,其中包括8名患者。有两名患者在接受了吡罗替尼治疗后获得了PR。没有发现影响派罗替尼 PFS 的独立因素。PDTOs证实了派罗替尼在HER2扩增的NSCLC肿瘤细胞中的抗肿瘤活性:结论:先前阿法替尼治疗后的病情进展不会影响派罗替尼的疗效。对于阿法替尼治疗后出现进展的HER2突变患者,派罗替尼可能是一种挽救选择。
{"title":"Pyrotinib as a salvage treatment for patients with HER-2 positive advanced lung adenocarcinoma after the progression of afatinib treatment.","authors":"Manyi Xu, Yanhua Wang, Keda Shao, Yue Hao, Zhengbo Song","doi":"10.1007/s12094-024-03482-9","DOIUrl":"10.1007/s12094-024-03482-9","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of afatinib or pyrotinib has been demonstrated in HER2-positive advanced non-small cell lung cancer (NSCLC) patients; however, the efficacy of pyrotinib after afatinib progression has yet to be determined.</p><p><strong>Method: </strong>Patients with HER2 mutated advanced lung adenocarcinoma administered afatinib or pyrotinib monotherapy were enrolled. Those who received pyrotinib after afatinib were further analyzed to determine the efficacy and safety of pyrotinib after progression on afatinib. Survival curves were plotted with the Kaplan-Meier method. A swimming plot was used to describe the specific treatments. Additionally, patient-derived tumor organoids (PDTOs) were established from HER2-amplified NSCLC patient samples to investigate the antitumor activity of pyrotinib in HER2-amplified tumor cells in vitro.</p><p><strong>Results: </strong>A total of 99 patients were enrolled, 13 of whom were administered pyrotinib after progression on afatinib. No statistical difference in PFS of pyrotinib was observed between patients whether be treated after afatinib progression or not (6.7 months vs. 4.4 months, P = 0.817), thus indicating that progression on afatinib did not affect the efficacy of pyrotinib. Further analysis was conducted on the former patients, which comprising eight patients administered interval chemotherapy after progression on afatinib. Two patients achieved PR after pyrotinib treatment. No independent factors were found to influence the PFS of pyrotinib. PDTOs confirmed the anti-tumor activity of pyrotinib in NSCLC tumor cells with HER2 amplification.</p><p><strong>Conclusions: </strong>Progression after prior afatinib treatment does not influence the efficacy of pyrotinib treatment. Pyrotinib may be a salvage option for patients with HER2 mutation who have experienced progression on afatinib.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3050-3057"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141096809","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}