Central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) is common. In our study, we built a nomogram to predict CLNM. We retrospectively analyzed 1,392 PTC patients. This group of patients was divided into a training cohort (including 1,009 patients) and a validation cohort (including 383 patients). Analyses of the correlation between inflammatory indicators, ultrasonic characteristics, pathological characteristics and CLNM were conducted. In the training cohort and validation cohort, the metastatic rates of CLNM were 60.16% and 64.23%, respectively. Univariate and multivariate logistic regression analyses demonstrated that Hashimoto’s thyroiditis (HT), calcification, multifocality, capsule invasion, PLR (platelet-lymphocyte ratio) ≤ 130.34, large tumors and middle and lower positions were independent risk factors for CLNM. Then, we constructed a nomogram. The nomogram had good discrimination regardless of whether there was CLNM, with a C-index of 0.809. The calibration curve indicated that the nomogram had good visual and quantitative consistency (p = 0.213). Decision curve analysis showed that the nomogram improved the net clinical benefit with a threshold probability of 0–82% in the training cohort and 0–71% in the validation cohort. We constructed a nomogram to predict CLNM in PTC and assist surgeons in making personalized clinical decisions for PTC.
{"title":"Nomogram to predict central lymph node metastasis in papillary thyroid carcinoma","authors":"Dehui Qiao, Xian Deng, Ruichen Liang, Xu Li, Rongjia Zhang, Zhi Lei, Hui Yang, Xiangyu Zhou","doi":"10.1007/s10585-024-10285-3","DOIUrl":"https://doi.org/10.1007/s10585-024-10285-3","url":null,"abstract":"<p>Central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) is common. In our study, we built a nomogram to predict CLNM. We retrospectively analyzed 1,392 PTC patients. This group of patients was divided into a training cohort (including 1,009 patients) and a validation cohort (including 383 patients). Analyses of the correlation between inflammatory indicators, ultrasonic characteristics, pathological characteristics and CLNM were conducted. In the training cohort and validation cohort, the metastatic rates of CLNM were 60.16% and 64.23%, respectively. Univariate and multivariate logistic regression analyses demonstrated that Hashimoto’s thyroiditis (HT), calcification, multifocality, capsule invasion, PLR (platelet-lymphocyte ratio) ≤ 130.34, large tumors and middle and lower positions were independent risk factors for CLNM. Then, we constructed a nomogram. The nomogram had good discrimination regardless of whether there was CLNM, with a C-index of 0.809. The calibration curve indicated that the nomogram had good visual and quantitative consistency (<i>p</i> = 0.213). Decision curve analysis showed that the nomogram improved the net clinical benefit with a threshold probability of 0–82% in the training cohort and 0–71% in the validation cohort. We constructed a nomogram to predict CLNM in PTC and assist surgeons in making personalized clinical decisions for PTC.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140582306","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 : 2024-04-01Epub Date: 2024-02-28DOI: 10.1007/s10585-024-10275-5
Shengcai Wei, Xinyi Gou, Yinli Zhang, Jingjing Cui, Xiaoming Liu, Nan Hong, Weiqi Sheng, Jin Cheng, Yi Wang
Chemotherapy alters the prognostic biomarker histopathological growth pattern (HGP) phenotype in colorectal liver metastases (CRLMs) patients. We aimed to develop a CT-based radiomics model to predict the transformation of the HGP phenotype after chemotherapy. This study included 181 patients with 298 CRLMs who underwent preoperative contrast-enhanced CT followed by partial hepatectomy between January 2007 and July 2022 at two institutions. HGPs were categorized as pure desmoplastic HGP (pdHGP) or non-pdHGP. The samples were allocated to training, internal validation, and external validation cohorts comprising 153, 65, and 29 CRLMs, respectively. Radiomics analysis was performed on pre-enhanced, arterial phase, portal venous phase (PVP), and fused images. The model was used to predict prechemotherapy HGPs in 112 CRLMs, and HGP transformation was analysed by comparing these findings with postchemotherapy HGPs determined pathologically. The prevalence of pdHGP was 19.8% (23/116) and 45.8% (70/153) in chemonaïve and postchemotherapy patients, respectively (P < 0.001). The PVP radiomics signature showed good performance in distinguishing pdHGP from non-pdHGPs (AUCs of 0.906, 0.877, and 0.805 in the training, internal validation, and external validation cohorts, respectively). The prevalence of prechemotherapy pdHGP predicted by the radiomics model was 33.0% (37/112), and the prevalence of postchemotherapy pdHGP according to the pathological analysis was 47.3% (53/112; P = 0.029). The transformation of HGP was bidirectional, with 15.2% (17/112) of CRLMs transforming from prechemotherapy pdHGP to postchemotherapy non-pdHGP and 30.4% (34/112) transforming from prechemotherapy non-pdHGP to postchemotherapy pdHGP (P = 0.005). CT-based radiomics method can be used to effectively predict the HGP transformation in chemotherapy-treated CRLM patients, thereby providing a basis for treatment decisions.
{"title":"Prediction of transformation in the histopathological growth pattern of colorectal liver metastases after chemotherapy using CT-based radiomics.","authors":"Shengcai Wei, Xinyi Gou, Yinli Zhang, Jingjing Cui, Xiaoming Liu, Nan Hong, Weiqi Sheng, Jin Cheng, Yi Wang","doi":"10.1007/s10585-024-10275-5","DOIUrl":"10.1007/s10585-024-10275-5","url":null,"abstract":"<p><p>Chemotherapy alters the prognostic biomarker histopathological growth pattern (HGP) phenotype in colorectal liver metastases (CRLMs) patients. We aimed to develop a CT-based radiomics model to predict the transformation of the HGP phenotype after chemotherapy. This study included 181 patients with 298 CRLMs who underwent preoperative contrast-enhanced CT followed by partial hepatectomy between January 2007 and July 2022 at two institutions. HGPs were categorized as pure desmoplastic HGP (pdHGP) or non-pdHGP. The samples were allocated to training, internal validation, and external validation cohorts comprising 153, 65, and 29 CRLMs, respectively. Radiomics analysis was performed on pre-enhanced, arterial phase, portal venous phase (PVP), and fused images. The model was used to predict prechemotherapy HGPs in 112 CRLMs, and HGP transformation was analysed by comparing these findings with postchemotherapy HGPs determined pathologically. The prevalence of pdHGP was 19.8% (23/116) and 45.8% (70/153) in chemonaïve and postchemotherapy patients, respectively (P < 0.001). The PVP radiomics signature showed good performance in distinguishing pdHGP from non-pdHGPs (AUCs of 0.906, 0.877, and 0.805 in the training, internal validation, and external validation cohorts, respectively). The prevalence of prechemotherapy pdHGP predicted by the radiomics model was 33.0% (37/112), and the prevalence of postchemotherapy pdHGP according to the pathological analysis was 47.3% (53/112; P = 0.029). The transformation of HGP was bidirectional, with 15.2% (17/112) of CRLMs transforming from prechemotherapy pdHGP to postchemotherapy non-pdHGP and 30.4% (34/112) transforming from prechemotherapy non-pdHGP to postchemotherapy pdHGP (P = 0.005). CT-based radiomics method can be used to effectively predict the HGP transformation in chemotherapy-treated CRLM patients, thereby providing a basis for treatment decisions.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982511","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 : 2024-04-01Epub Date: 2024-02-14DOI: 10.1007/s10585-024-10274-6
Joshua S Suppree, Siddarth Kannan, David M Hughes, Michael D Jenkinson, Rasheed Zakaria
Brain metastases represent a growing healthcare challenge with a rising incidence attributed to earlier detection and improved systemic cancer treatments. We conducted a systematic review and meta-analysis to investigate the local recurrence rate following surgical resection of a brain metastasis without adjuvant therapy. The analysis included four studies with a total of 235 cases. It was found that the rate of local recurrence by 12-months was 48.1% (95% CI 41.2-58.9). These findings underscore the high rate of patients who will experience local recurrence within 12-months of surgery, emphasising the need for vigilant surveillance when omitting adjuvant radiotherapy in favour of systemic treatments with potential but unproven CNS penetrance. The analysis highlights unmet needs in this patient population.
脑转移瘤是一项日益严峻的医疗挑战,其发病率的上升归因于早期发现和系统性癌症治疗方法的改进。我们进行了一项系统性回顾和荟萃分析,以研究在不进行辅助治疗的情况下,手术切除脑转移瘤后的局部复发率。分析包括四项研究,共 235 个病例。结果发现,12 个月后的局部复发率为 48.1%(95% CI 41.2-58.9)。这些研究结果表明,手术后12个月内出现局部复发的患者比例很高,强调在放弃辅助放疗而选择具有潜在但未经证实的中枢神经系统穿透性的全身治疗时,需要进行警惕性监测。该分析凸显了这一患者群体尚未得到满足的需求。
{"title":"Letter: Estimating the baseline local recurrence rate for a brain metastasis after neurosurgical resection.","authors":"Joshua S Suppree, Siddarth Kannan, David M Hughes, Michael D Jenkinson, Rasheed Zakaria","doi":"10.1007/s10585-024-10274-6","DOIUrl":"10.1007/s10585-024-10274-6","url":null,"abstract":"<p><p>Brain metastases represent a growing healthcare challenge with a rising incidence attributed to earlier detection and improved systemic cancer treatments. We conducted a systematic review and meta-analysis to investigate the local recurrence rate following surgical resection of a brain metastasis without adjuvant therapy. The analysis included four studies with a total of 235 cases. It was found that the rate of local recurrence by 12-months was 48.1% (95% CI 41.2-58.9). These findings underscore the high rate of patients who will experience local recurrence within 12-months of surgery, emphasising the need for vigilant surveillance when omitting adjuvant radiotherapy in favour of systemic treatments with potential but unproven CNS penetrance. The analysis highlights unmet needs in this patient population.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729129","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 : 2024-04-01Epub Date: 2024-02-16DOI: 10.1007/s10585-024-10266-6
Michele Maffezzoli, Matteo Santoni, Giulia Mazzaschi, Sara Rodella, Eleonora Lai, Marco Maruzzo, Umberto Basso, Davide Bimbatti, Roberto Iacovelli, Annunziato Anghelone, Ondřej Fiala, Sara Elena Rebuzzi, Giuseppe Fornarini, Cristian Lolli, Francesco Massari, Matteo Rosellini, Veronica Mollica, Cecilia Nasso, Alessandro Acunzo, Enrico Maria Silini, Federico Quaini, Massimo De Filippo, Matteo Brunelli, Giuseppe L Banna, Pasquale Rescigno, Alessio Signori, Sebastiano Buti
Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients' counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI). We performed a sub-analysis of a multicentre retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations. Uni- and multivariable Cox regression models were used to assess the correlation between the red cell-based score and progression-free survival (PFS), and overall survival (OS). Logistic regression were used to estimate the correlation between the score and the objective response rate (ORR). The prognostic impact of the red cell-based score on PFS and OS was confirmed in the whole population regardless of the immunotherapy combination used [median PFS (mPFS): 17.4 vs 8.2 months, HR 0.66, 95% CI 0.47-0.94; median OS (mOS): 42.0 vs 17.3 months, HR 0.60, 95% CI 0.39-0.92; p < 0.001 for both]. We validated the prognostic significance of the red cell-based score in patients with mRCC treated with first-line immunotherapy combinations. The score is easy to use in daily clinical practice and it might improve patient counselling.
酪氨酸激酶抑制剂(TKIs)和免疫检查点抑制剂(ICIs)的免疫疗法组合能显著改善mRCC患者的预后。预测和预后因素对改善患者的咨询和管理至关重要。本研究旨在从外部验证之前开发的基于红细胞的评分,包括血红蛋白(Hb)、平均血球容积(MCV)和红细胞分布宽度(RDW),在接受一线免疫疗法组合(TKI 加 ICI 或 ICI 加 ICI)治疗的 mRCC 患者中的预后价值。我们对一项多中心回顾性观察研究(ARON-1 项目)进行了子分析,该研究涉及接受一线免疫疗法组合治疗的 mRCC 患者。我们使用单变量和多变量Cox回归模型评估了基于红细胞的评分与无进展生存期(PFS)和总生存期(OS)之间的相关性。逻辑回归用于估计评分与客观反应率(ORR)之间的相关性。无论使用哪种免疫疗法组合,红细胞评分对PFS和OS的预后影响在整个人群中都得到了证实[中位PFS(mPFS):17.4 vs 8.2个月,HR 0.66,95% CI 0.47-0.94;中位OS(mOS):42.0 vs 17.3个月,HR 0.66,95% CI 0.47-0.94;中位OS(mOS):42.0 vs 17.3个月,HR 0.66,95% CI 0.47-0.94]:42.0 个月 vs 17.3 个月,HR 0.60,95% CI 0.39-0.92; p
{"title":"External validation of a red cell-based blood prognostic score in patients with metastatic renal cell carcinoma treated with first-line immunotherapy combinations.","authors":"Michele Maffezzoli, Matteo Santoni, Giulia Mazzaschi, Sara Rodella, Eleonora Lai, Marco Maruzzo, Umberto Basso, Davide Bimbatti, Roberto Iacovelli, Annunziato Anghelone, Ondřej Fiala, Sara Elena Rebuzzi, Giuseppe Fornarini, Cristian Lolli, Francesco Massari, Matteo Rosellini, Veronica Mollica, Cecilia Nasso, Alessandro Acunzo, Enrico Maria Silini, Federico Quaini, Massimo De Filippo, Matteo Brunelli, Giuseppe L Banna, Pasquale Rescigno, Alessio Signori, Sebastiano Buti","doi":"10.1007/s10585-024-10266-6","DOIUrl":"10.1007/s10585-024-10266-6","url":null,"abstract":"<p><p>Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients' counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI). We performed a sub-analysis of a multicentre retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations. Uni- and multivariable Cox regression models were used to assess the correlation between the red cell-based score and progression-free survival (PFS), and overall survival (OS). Logistic regression were used to estimate the correlation between the score and the objective response rate (ORR). The prognostic impact of the red cell-based score on PFS and OS was confirmed in the whole population regardless of the immunotherapy combination used [median PFS (mPFS): 17.4 vs 8.2 months, HR 0.66, 95% CI 0.47-0.94; median OS (mOS): 42.0 vs 17.3 months, HR 0.60, 95% CI 0.39-0.92; p < 0.001 for both]. We validated the prognostic significance of the red cell-based score in patients with mRCC treated with first-line immunotherapy combinations. The score is easy to use in daily clinical practice and it might improve patient counselling.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740566","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 : 2024-04-01Epub Date: 2024-02-29DOI: 10.1007/s10585-024-10273-7
Anton Burkhard-Meier, Vindi Jurinovic, Luc M Berclaz, Markus Albertsmeier, Hans Roland Dürr, Alexander Klein, Thomas Knösel, Dorit Di Gioia, Lena M Unterrainer, Nina-Sophie Schmidt-Hegemann, Jens Ricke, Michael von Bergwelt-Baildon, Wolfgang G Kunz, Lars H Lindner
Lymph node metastasis (LNM) occurs in less than 5% of soft tissue sarcoma (STS) patients and indicates an aggressive course of disease. Suspicious lymph nodes (LN) in staging imaging are a frequent topic of discussion in multidisciplinary tumor boards. Predictive markers are needed to facilitate stratification and improve treatment of STS patients. In this study, 56 STS patients with radiologically suspicious and subsequently histologically examined LN were reviewed. Patients with benign (n = 26) and metastatic (n = 30) LN were analyzed with regard to clinical, laboratory and imaging parameters. Patients with LNM exhibited significantly larger short axis diameter (SAD) and long axis diameter (LAD) vs. patients with benign LN (median 22.5 vs. 14 mm, p < 0.001 and median 29.5 vs. 21 mm, p = 0.003, respectively). Furthermore, the presence of central necrosis and high maximal standardized uptake value (SUVmax) in FDG-PET-CT scans were significantly associated with LNM (60 vs. 11.5% of patients, p < 0.001 and median 8.59 vs. 3.96, p = 0.013, respectively). With systemic therapy, a slight median size regression over time was observed in both metastatic and benign LN. Serum LDH and CRP levels were significantly higher in patients with LNM (median 247 vs. 187.5U/L, p = 0.005 and 1.5 vs. 0.55 mg/dL, p = 0.039, respectively). This study shows significant associations between LNM and imaging features as well as laboratory parameters of STS patients. The largest SAD, SUVmax in FDG-PET-CT scan, the presence of central necrosis, and high serum LDH level are the most important parameters to distinguish benign from metastatic LNs.
{"title":"Differentiation of benign and metastatic lymph nodes in soft tissue sarcoma.","authors":"Anton Burkhard-Meier, Vindi Jurinovic, Luc M Berclaz, Markus Albertsmeier, Hans Roland Dürr, Alexander Klein, Thomas Knösel, Dorit Di Gioia, Lena M Unterrainer, Nina-Sophie Schmidt-Hegemann, Jens Ricke, Michael von Bergwelt-Baildon, Wolfgang G Kunz, Lars H Lindner","doi":"10.1007/s10585-024-10273-7","DOIUrl":"10.1007/s10585-024-10273-7","url":null,"abstract":"<p><p>Lymph node metastasis (LNM) occurs in less than 5% of soft tissue sarcoma (STS) patients and indicates an aggressive course of disease. Suspicious lymph nodes (LN) in staging imaging are a frequent topic of discussion in multidisciplinary tumor boards. Predictive markers are needed to facilitate stratification and improve treatment of STS patients. In this study, 56 STS patients with radiologically suspicious and subsequently histologically examined LN were reviewed. Patients with benign (n = 26) and metastatic (n = 30) LN were analyzed with regard to clinical, laboratory and imaging parameters. Patients with LNM exhibited significantly larger short axis diameter (SAD) and long axis diameter (LAD) vs. patients with benign LN (median 22.5 vs. 14 mm, p < 0.001 and median 29.5 vs. 21 mm, p = 0.003, respectively). Furthermore, the presence of central necrosis and high maximal standardized uptake value (SUVmax) in FDG-PET-CT scans were significantly associated with LNM (60 vs. 11.5% of patients, p < 0.001 and median 8.59 vs. 3.96, p = 0.013, respectively). With systemic therapy, a slight median size regression over time was observed in both metastatic and benign LN. Serum LDH and CRP levels were significantly higher in patients with LNM (median 247 vs. 187.5U/L, p = 0.005 and 1.5 vs. 0.55 mg/dL, p = 0.039, respectively). This study shows significant associations between LNM and imaging features as well as laboratory parameters of STS patients. The largest SAD, SUVmax in FDG-PET-CT scan, the presence of central necrosis, and high serum LDH level are the most important parameters to distinguish benign from metastatic LNs.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989488","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 : 2024-04-01Epub Date: 2024-02-24DOI: 10.1007/s10585-024-10280-8
Xiaoman Zhang, Cuicui Xu, Cuicui Wang, Yuhui Pei, Min He, Zhicheng Wan, Jun Hou, Lianghai Wang
Objective: Aberrant expression of CD276 has been reported in malignant tumors. However, the exact role and mechanisms of CD276 influence the progression of esophageal squamous cell carcinoma (ESCC) still need to be understood.
Methods: Bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus databases, along with immunohistochemistry staining, was used to explore the expression patterns of CD276 in ESCC. Cell counting kit-8 and Transwell assays were employed to evaluate the effects of CD276 expression on tumor cell proliferation and motility. Western blotting and Transwell assays were used to explore the potential pathways through which CD276 mediates the progression of ESCC. Moreover, the in vivo role of CD276 in tumor progression was investigated by establishing a lung metastasis mouse model.
Results: A significant upregulation of CD276 was observed in ESCC tissues compared to adjacent tissues. The inhibition of CD276 had no evident impact on ESCC cell proliferation but notably hindered their migratory and invasive properties and the expression of epithelial-mesenchymal transition (EMT) markers. Inversely, overexpressing CD276 led to an upregulation of EMT markers, underscoring the capacity of CD276 to amplify the motility of ESCC cells. Furthermore, CD276 was found to enhance the migratory and invasive abilities of ESCC cells by activating the TGF-β/SMAD signaling but not the PI3K/AKT pathway. In vivo studies demonstrated that CD276 facilitates pulmonary metastasis.
Conclusion: CD276 is significant upregulation in ESCC tissues and facilitates the EMT process in ESCC cells via the TGF-β/SMAD signaling, thus promoting the progression of ESCC.
{"title":"CD276 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma through the TGF-β/SMAD signaling.","authors":"Xiaoman Zhang, Cuicui Xu, Cuicui Wang, Yuhui Pei, Min He, Zhicheng Wan, Jun Hou, Lianghai Wang","doi":"10.1007/s10585-024-10280-8","DOIUrl":"10.1007/s10585-024-10280-8","url":null,"abstract":"<p><strong>Objective: </strong>Aberrant expression of CD276 has been reported in malignant tumors. However, the exact role and mechanisms of CD276 influence the progression of esophageal squamous cell carcinoma (ESCC) still need to be understood.</p><p><strong>Methods: </strong>Bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus databases, along with immunohistochemistry staining, was used to explore the expression patterns of CD276 in ESCC. Cell counting kit-8 and Transwell assays were employed to evaluate the effects of CD276 expression on tumor cell proliferation and motility. Western blotting and Transwell assays were used to explore the potential pathways through which CD276 mediates the progression of ESCC. Moreover, the in vivo role of CD276 in tumor progression was investigated by establishing a lung metastasis mouse model.</p><p><strong>Results: </strong>A significant upregulation of CD276 was observed in ESCC tissues compared to adjacent tissues. The inhibition of CD276 had no evident impact on ESCC cell proliferation but notably hindered their migratory and invasive properties and the expression of epithelial-mesenchymal transition (EMT) markers. Inversely, overexpressing CD276 led to an upregulation of EMT markers, underscoring the capacity of CD276 to amplify the motility of ESCC cells. Furthermore, CD276 was found to enhance the migratory and invasive abilities of ESCC cells by activating the TGF-β/SMAD signaling but not the PI3K/AKT pathway. In vivo studies demonstrated that CD276 facilitates pulmonary metastasis.</p><p><strong>Conclusion: </strong>CD276 is significant upregulation in ESCC tissues and facilitates the EMT process in ESCC cells via the TGF-β/SMAD signaling, thus promoting the progression of ESCC.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139939766","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 : 2024-04-01Epub Date: 2024-02-14DOI: 10.1007/s10585-024-10268-4
Marie-Therese Haider, Vera Freytag, Linda Krause, Tanja Spethmann, Tobias Gosau, Mia C Beine, Christine Knies, Jennifer Schröder-Schwarz, Michael Horn, Kristoffer Riecken, Tobias Lange
Bioluminescence imaging (BLI) is a non-invasive state-of-the-art-method for longitudinal tracking of tumor cells in mice. The technique is commonly used to determine bone metastatic burden in vivo and also suitable ex vivo to detect even smallest bone micro-metastases in spontaneous metastasis xenograft models. However, it is unclear to which extent ex vivo BLI correlates with alternative methods for metastasis quantification. Here, we compared ex vivo BLI, human DNA-based Alu-qPCR, and histology for the quantification of bone vs. lung metastases, which are amongst the most common sites of metastasis in prostate cancer (PCa) patients and spontaneous PCa xenograft models. Data from 93 immunodeficient mice were considered, each of which were subcutaneously injected with luciferase/RGB-labeled human PCa PC-3 cells. The primary tumors were resected at ~ 0.75 cm³ and mice were sacrificed ~ 3 weeks after surgery and immediately examined by ex vivo BLI. Afterwards, the right lungs and hind limbs with the higher BLI signal (BLIHi bone) were processed for histology, whereas the left lung lobes and hind limbs with the lower BLI signal (BLILo bone) were prepared for Alu-qPCR. Our data demonstrate remarkable differences in the correlation coefficients of the different methods for lung metastasis detection (r ~ 0.8) vs. bone metastasis detection (r ~ 0.4). However, the BLI values of the BLIHi and BLILo bones correlated very strongly (r ~ 0.9), indicating that the method per se was reliable under identical limitations; the overall level of metastasis to contralateral bones was astonishingly similar. Instead, the level of lung metastasis only weakly to moderately correlated with the level of bone metastasis formation. Summarized, we observed a considerable discrepancy between ex vivo BLI and histology/Alu-qPCR in the quantification of bone metastases, which was not observed in the case of lung metastases. Future studies using ex vivo BLI for bone metastasis quantification should combine multiple methods to accurately determine metastatic load in bone samples.
生物发光成像(BLI)是纵向追踪小鼠体内肿瘤细胞的无创先进方法。该技术通常用于确定体内骨转移负荷,也适用于体外检测自发转移异种移植模型中最小的骨微小转移灶。然而,目前还不清楚体内外 BLI 与其他转移量化方法的相关程度。在这里,我们比较了体内外 BLI、基于人类 DNA 的 Alu-qPCR 和组织学对骨转移和肺转移的定量,骨转移是前列腺癌(PCa)患者和自发性 PCa 异种移植模型中最常见的转移部位之一。研究考虑了 93 只免疫缺陷小鼠的数据,每只小鼠都皮下注射了荧光素酶/RGB 标记的人类 PCa PC-3 细胞。原发肿瘤约 0.75 立方厘米处被切除,小鼠在手术后约 3 周被处死,并立即进行体外 BLI 检查。随后,对 BLI 信号较高的右肺和后肢(BLIHi 骨)进行组织学处理,而对 BLI 信号较低的左肺叶和后肢(BLILo 骨)进行 Alu-qPCR 处理。我们的数据表明,在肺转移瘤检测(r ~ 0.8)与骨转移瘤检测(r ~ 0.4)中,不同方法的相关系数存在明显差异。然而,BLIHi 和 BLILo 骨的 BLI 值相关性非常强(r ~ 0.9),这表明在相同的限制条件下,该方法本身是可靠的;对侧骨转移的总体水平惊人地相似。相反,肺转移水平与骨转移形成水平只有微弱到中等程度的相关性。总之,我们观察到体内外 BLI 和组织学/Alu-qPCR 在骨转移的量化方面存在相当大的差异,而在肺转移的情况中却没有观察到这种差异。未来使用体外 BLI 定量骨转移的研究应结合多种方法,以准确确定骨样本中的转移负荷。
{"title":"Comparison of ex vivo bioluminescence imaging, Alu-qPCR and histology for the quantification of spontaneous lung and bone metastases in subcutaneous xenograft mouse models.","authors":"Marie-Therese Haider, Vera Freytag, Linda Krause, Tanja Spethmann, Tobias Gosau, Mia C Beine, Christine Knies, Jennifer Schröder-Schwarz, Michael Horn, Kristoffer Riecken, Tobias Lange","doi":"10.1007/s10585-024-10268-4","DOIUrl":"10.1007/s10585-024-10268-4","url":null,"abstract":"<p><p>Bioluminescence imaging (BLI) is a non-invasive state-of-the-art-method for longitudinal tracking of tumor cells in mice. The technique is commonly used to determine bone metastatic burden in vivo and also suitable ex vivo to detect even smallest bone micro-metastases in spontaneous metastasis xenograft models. However, it is unclear to which extent ex vivo BLI correlates with alternative methods for metastasis quantification. Here, we compared ex vivo BLI, human DNA-based Alu-qPCR, and histology for the quantification of bone vs. lung metastases, which are amongst the most common sites of metastasis in prostate cancer (PCa) patients and spontaneous PCa xenograft models. Data from 93 immunodeficient mice were considered, each of which were subcutaneously injected with luciferase/RGB-labeled human PCa PC-3 cells. The primary tumors were resected at ~ 0.75 cm³ and mice were sacrificed ~ 3 weeks after surgery and immediately examined by ex vivo BLI. Afterwards, the right lungs and hind limbs with the higher BLI signal (BLI<sup>Hi</sup> bone) were processed for histology, whereas the left lung lobes and hind limbs with the lower BLI signal (BLI<sup>Lo</sup> bone) were prepared for Alu-qPCR. Our data demonstrate remarkable differences in the correlation coefficients of the different methods for lung metastasis detection (r ~ 0.8) vs. bone metastasis detection (r ~ 0.4). However, the BLI values of the BLI<sup>Hi</sup> and BLI<sup>Lo</sup> bones correlated very strongly (r ~ 0.9), indicating that the method per se was reliable under identical limitations; the overall level of metastasis to contralateral bones was astonishingly similar. Instead, the level of lung metastasis only weakly to moderately correlated with the level of bone metastasis formation. Summarized, we observed a considerable discrepancy between ex vivo BLI and histology/Alu-qPCR in the quantification of bone metastases, which was not observed in the case of lung metastases. Future studies using ex vivo BLI for bone metastasis quantification should combine multiple methods to accurately determine metastatic load in bone samples.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10972982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729128","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 : 2024-03-29DOI: 10.1007/s10585-024-10279-1
Sophia Leduc, Ha-Linh Nguyen, François Richard, Gitte Zels, Amena Mahdami, Maxim De Schepper, Marion Maetens, Anirudh Pabba, Joris Jaekers, Emily Latacz, Ali Bohlok, Evy Vanderheyden, Thomas Van Brussel, Bram Boeckx, Rogier Schepers, Diether Lambrechts, Luc Dirix, Denis Larsimont, Sophie Vankerckhove, Valerio Lucidi, Baki Topal, Imane Bachir, Vincent Donckier, Giuseppe Floris, Peter Vermeulen, Christine Desmedt
Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM.
{"title":"Transcriptomic characterization of the histopathological growth patterns in breast cancer liver metastases.","authors":"Sophia Leduc, Ha-Linh Nguyen, François Richard, Gitte Zels, Amena Mahdami, Maxim De Schepper, Marion Maetens, Anirudh Pabba, Joris Jaekers, Emily Latacz, Ali Bohlok, Evy Vanderheyden, Thomas Van Brussel, Bram Boeckx, Rogier Schepers, Diether Lambrechts, Luc Dirix, Denis Larsimont, Sophie Vankerckhove, Valerio Lucidi, Baki Topal, Imane Bachir, Vincent Donckier, Giuseppe Floris, Peter Vermeulen, Christine Desmedt","doi":"10.1007/s10585-024-10279-1","DOIUrl":"https://doi.org/10.1007/s10585-024-10279-1","url":null,"abstract":"<p><p>Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317902","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 : 2024-03-18DOI: 10.1007/s10585-024-10277-3
Sven Jacob, Ilja Balonov, Vindi Jurinovic, Christian Heiliger, Tengis Tschaidse, Jörg Kumbrink, Thomas Kirchner, Jens Werner, Martin K. Angele, Marlies Michl, Jens Neumann
Rationale
Colorectal Cancer (CRC) represents the third most common type of cancer in Germany and the second most common cancer-related cause of death worldwide. Distant metastases are still the main limit for patient survival. While liver metastases as well as peritoneal carcinomatosis can often either be resected or treated with systemic therapy, little options remain for brain metastases. Additionally, a number of studies has already investigated hepatic, peritoneal, pulmonary as well as continuing distant metastases in colorectal cancer. Yet, with respect to tumor biology and brain metastases, little is known so far.
Material and methods
Two cohorts, M0 without distant spread and BRA with brain metastases were build. RNA was isolated from paraffin embedded specimen. Gene expression was performed by an RNA NanoString-Analysis using the nCounter® PanCancer Progression Panel by NanoString-Technologies (Hamburg, Germany). Results were analysed by principal component analysis, gene expression and pathway analysis using commonly available databases such as KEGG as benchmark for comparison.
Results
We were able to determine a gene signature that provides a sophisticated group separation between M0 and BRA using principal component analysis. All genes with strong loading characteristics on principal component 1 were cross-referenced with the subsequently performed accurate gene set enrichment analysis (GSEA). The GSEA revealed a clear dysregulation of the TGFβ pathway in compared cohorts M0 and BRA. Interestingly, the targeted pathways analysis of the identified genes confirmed that in fact almost all strong loading genes of PC1 play a role in the TGFβ pathway.
Conclusion
Our results suggest the TGFβ pathway as a crucial player in the development of brain metastases in primary CRC. In some types of colorectal cancer, downregulation of the TGFβ pathway might hinder primary colorectal cancer to metastasize to the nervous system. While the paradoxical functioning of the TGFβ pathway is still not fully understood, these shed light on yet another clinical implication of this complex pathway.
{"title":"TGFβ signalling pathway impacts brain metastases profiles in locally advanced colorectal cancer","authors":"Sven Jacob, Ilja Balonov, Vindi Jurinovic, Christian Heiliger, Tengis Tschaidse, Jörg Kumbrink, Thomas Kirchner, Jens Werner, Martin K. Angele, Marlies Michl, Jens Neumann","doi":"10.1007/s10585-024-10277-3","DOIUrl":"https://doi.org/10.1007/s10585-024-10277-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Rationale</h3><p>Colorectal Cancer (CRC) represents the third most common type of cancer in Germany and the second most common cancer-related cause of death worldwide. Distant metastases are still the main limit for patient survival. While liver metastases as well as peritoneal carcinomatosis can often either be resected or treated with systemic therapy, little options remain for brain metastases. Additionally, a number of studies has already investigated hepatic, peritoneal, pulmonary as well as continuing distant metastases in colorectal cancer. Yet, with respect to tumor biology and brain metastases, little is known so far.</p><h3 data-test=\"abstract-sub-heading\">Material and methods</h3><p>Two cohorts, M0 without distant spread and BRA with brain metastases were build. RNA was isolated from paraffin embedded specimen. Gene expression was performed by an RNA NanoString-Analysis using the nCounter® PanCancer Progression Panel by NanoString-Technologies (Hamburg, Germany). Results were analysed by principal component analysis, gene expression and pathway analysis using commonly available databases such as KEGG as benchmark for comparison.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We were able to determine a gene signature that provides a sophisticated group separation between M0 and BRA using principal component analysis. All genes with strong loading characteristics on principal component 1 were cross-referenced with the subsequently performed accurate gene set enrichment analysis (GSEA). The GSEA revealed a clear dysregulation of the TGFβ pathway in compared cohorts M0 and BRA. Interestingly, the targeted pathways analysis of the identified genes confirmed that in fact almost all strong loading genes of PC1 play a role in the TGFβ pathway.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our results suggest the TGFβ pathway as a crucial player in the development of brain metastases in primary CRC. In some types of colorectal cancer, downregulation of the TGFβ pathway might hinder primary colorectal cancer to metastasize to the nervous system. While the paradoxical functioning of the TGFβ pathway is still not fully understood, these shed light on yet another clinical implication of this complex pathway.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140154242","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 : 2024-03-15DOI: 10.1007/s10585-024-10269-3
Sarah Libring, Emily D Berestesky, Cynthia A Reinhart-King
As a major energy source for cells, mitochondria are involved in cell growth and proliferation, as well as migration, cell fate decisions, and many other aspects of cellular function. Once thought to be irreparably defective, mitochondrial function in cancer cells has found renewed interest, from suggested potential clinical biomarkers to mitochondria-targeting therapies. Here, we will focus on the effect of mitochondria movement on breast cancer progression. Mitochondria move both within the cell, such as to localize to areas of high energetic need, and between cells, where cells within the stroma have been shown to donate their mitochondria to breast cancer cells via multiple methods including tunneling nanotubes. The donation of mitochondria has been seen to increase the aggressiveness and chemoresistance of breast cancer cells, which has increased recent efforts to uncover the mechanisms of mitochondrial transfer. As metabolism and energetics are gaining attention as clinical targets, a better understanding of mitochondrial function and implications in cancer are required for developing effective, targeted therapeutics for cancer patients.
{"title":"The movement of mitochondria in breast cancer: internal motility and intercellular transfer of mitochondria.","authors":"Sarah Libring, Emily D Berestesky, Cynthia A Reinhart-King","doi":"10.1007/s10585-024-10269-3","DOIUrl":"https://doi.org/10.1007/s10585-024-10269-3","url":null,"abstract":"<p><p>As a major energy source for cells, mitochondria are involved in cell growth and proliferation, as well as migration, cell fate decisions, and many other aspects of cellular function. Once thought to be irreparably defective, mitochondrial function in cancer cells has found renewed interest, from suggested potential clinical biomarkers to mitochondria-targeting therapies. Here, we will focus on the effect of mitochondria movement on breast cancer progression. Mitochondria move both within the cell, such as to localize to areas of high energetic need, and between cells, where cells within the stroma have been shown to donate their mitochondria to breast cancer cells via multiple methods including tunneling nanotubes. The donation of mitochondria has been seen to increase the aggressiveness and chemoresistance of breast cancer cells, which has increased recent efforts to uncover the mechanisms of mitochondrial transfer. As metabolism and energetics are gaining attention as clinical targets, a better understanding of mitochondrial function and implications in cancer are required for developing effective, targeted therapeutics for cancer patients.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136571","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}