Cancer & Metabolism最新文献

{"title":"Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response.","authors":"Ceren Yalaz, Esther Bridges, Nasullah K Alham, Christos E Zois, Jianzhou Chen, Karim Bensaad, Ana Miar, Elisabete Pires, Ruth J Muschel, James S O McCullagh, Adrian L Harris","doi":"10.1186/s40170-023-00326-y","DOIUrl":"10.1186/s40170-023-00326-y","url":null,"abstract":"<p><strong>Background: </strong>PDE6H encodes PDE6γ', the inhibitory subunit of the cGMP-specific phosphodiesterase 6 in cone photoreceptors. Inhibition of PDE6, which has been widely studied for its role in light transduction, increases cGMP levels. The purpose of this study is to characterise the role of PDE6H in cancer cell growth.</p><p><strong>Methods: </strong>From an siRNA screen for 487 genes involved in metabolism, PDE6H was identified as a controller of cell cycle progression in HCT116 cells. Role of PDE6H in cancer cell growth and metabolism was studied through the effects of its depletion on levels of cell cycle controllers, mTOR effectors, metabolite levels, and metabolic energy assays. Effect of PDE6H deletion on tumour growth was also studied in a xenograft model.</p><p><strong>Results: </strong>PDE6H knockout resulted in an increase of intracellular cGMP levels, as well as changes to the levels of nucleotides and key energy metabolism intermediates. PDE6H knockdown induced G1 cell cycle arrest and cell death and reduced mTORC1 signalling in cancer cell lines. Both knockdown and knockout of PDE6H resulted in the suppression of mitochondrial function. HCT116 xenografts revealed that PDE6H deletion, as well as treatment with the PDE5/6 inhibitor sildenafil, slowed down tumour growth and improved survival, while sildenafil treatment did not have an additive effect on slowing the growth of PDE6γ'-deficient tumours.</p><p><strong>Conclusions: </strong>Our results indicate that the changes in cGMP and purine pools, as well as mitochondrial function which is observed upon PDE6γ' depletion, are independent of the PKG pathway. We show that in HCT116, PDE6H deletion replicates many effects of the dark retina response and identify PDE6H as a new target in preventing cancer cell proliferation and tumour growth.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"12 1","pages":"5"},"PeriodicalIF":5.9,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729060","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}

{"title":"Circulating metabolome landscape in Lynch syndrome.","authors":"Tiina A Jokela, Jari E Karppinen, Minta Kärkkäinen, Jukka-Pekka Mecklin, Simon Walker, Toni T Seppälä, Eija K Laakkonen","doi":"10.1186/s40170-024-00331-9","DOIUrl":"10.1186/s40170-024-00331-9","url":null,"abstract":"<p><p>Circulating metabolites systemically reflect cellular processes and can modulate the tissue microenvironment in complex ways, potentially impacting cancer initiation processes. Genetic background increases cancer risk in individuals with Lynch syndrome; however, not all carriers develop cancer. Various lifestyle factors can influence Lynch syndrome cancer risk, and lifestyle choices actively shape systemic metabolism, with circulating metabolites potentially serving as the mechanical link between lifestyle and cancer risk. This study aims to characterize the circulating metabolome of Lynch syndrome carriers, shedding light on the energy metabolism status in this cancer predisposition syndrome.This study consists of a three-group cross-sectional analysis to compare the circulating metabolome of cancer-free Lynch syndrome carriers, sporadic colorectal cancer (CRC) patients, and healthy non-carrier controls. We detected elevated levels of circulating cholesterol, lipids, and lipoproteins in LS carriers. Furthermore, we unveiled that Lynch syndrome carriers and CRC patients displayed similar alterations compared to healthy non-carriers in circulating amino acid and ketone body profiles. Overall, cancer-free Lynch syndrome carriers showed a unique circulating metabolome landscape.This study provides valuable insights into the systemic metabolic landscape of Lynch syndrome individuals. The findings hint at shared metabolic patterns between cancer-free Lynch syndrome carriers and CRC patients.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"12 1","pages":"4"},"PeriodicalIF":5.9,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691219","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}

{"title":"Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia","authors":"Guo-Tian Ruan, Li Deng, Hai-Lun Xie, Jin-Yu Shi, Xiao-Yue Liu, Xin Zheng, Yue Chen, Shi-Qi Lin, He-Yang Zhang, Chen-An Liu, Yi-Zhong Ge, Meng-Meng Song, Chun-Lei Hu, Xiao-Wei Zhang, Ming Yang, Wen Hu, Ming-Hua Cong, Li-Chen Zhu, Kun-Hua Wang, Han-Ping Shi","doi":"10.1186/s40170-024-00332-8","DOIUrl":"https://doi.org/10.1186/s40170-024-00332-8","url":null,"abstract":"The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13–1.33), 34% (internal test cohort, 95%CI = 1.11–1.62), and 35% (external validation cohort, 95%CI = 1.14–1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22–1.71; internal test cohort, HR = 1.62, 95%CI = 1.12–2.36; external validation cohort, HR = 1.61, 95%CI = 1.15–2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05–4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42–3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52–4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24–2.55] in patients with cancer cachexia. The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"11 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557563","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}

{"title":"Deficiency of TOP1MT enhances glycolysis through the stimulation of PDK4 expression in gastric cancer","authors":"Hongqiang Wang, Xutao Sun, Chen Yang, Ziqi Li, Danwen Jin, Wenwen Zhu, Ze Yu","doi":"10.1186/s40170-024-00330-w","DOIUrl":"https://doi.org/10.1186/s40170-024-00330-w","url":null,"abstract":"Abnormal glucose metabolism is one of the determinants of maintaining malignant characteristics of cancer. Targeting cancer metabolism is regarded as a new strategy for cancer treatment. Our previous studies have found that TOP1MT is a crucial gene that inhibits glycolysis and cell metastasis of gastric cancer (GC) cells, but the mechanism of its regulation of glycolysis remains unclear. Transcriptome sequencing data, clinic-pathologic features of GC from a variety of public databases, and WGCNA were used to identify novel targets of TOP1MT. Immunohistochemical results of 250 patients with GC were used to analyze the relative expression relationship between TOP1MT and PDK4. The function of TOP1MT was investigated by migration assays and sea-horse analysis in vitro. We discovered a mitochondrial topoisomerase I, TOP1MT, which correlated with a higher risk of metastasis. Functional experiments revealed that TOP1MT deficiency promotes cell migration and glycolysis through increasing PDK4 expression. Additionally, the stimulating effect of TOP1MT on glycolysis may be effectively reversed by PDK4 inhibitor M77976. In brief, our work demonstrated the critical function of TOP1MT in the regulation of glycolysis by PDK4 in gastric cancer. Inhibiting glycolysis and limiting tumor metastasis in GC may be accomplished by suppressing PDK4.","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"54 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139412858","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}

{"title":"Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer","authors":"Federica Tambaro, Giovanni Imbimbo, Elisabetta Ferraro, Martina Andreini, Roberta Belli, Maria Ida Amabile, Cesarina Ramaccini, Giulia Lauteri, Giuseppe Nigri, Maurizio Muscaritoli, Alessio Molfino","doi":"10.1186/s40170-023-00329-9","DOIUrl":"https://doi.org/10.1186/s40170-023-00329-9","url":null,"abstract":"Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different types of GI cancers, and in cachexia. We considered patients with GI cancer (gastric, pancreatic, and colorectal) at their first diagnosis, with/without cachexia, and controls with benign diseases. We collected SAT and total RNA was extracted and ATGL, HSL, PPARα, and MCP1 were analyzed by qRT-PCR. Western blot was performed to evaluate CGI-58, PLIN1 and PLIN5. We found higher expression of ATGL and HSL in GI cancer patients with respect to controls (p ≤ 0.008) and a trend of increase for PPARα (p = 0.055). We found an upregulation of ATGL in GI cancer patients with cachexia (p = 0.033) and without cachexia (p = 0.017) vs controls. HSL was higher in patients with cachexia (p = 0.020) and without cachexia (p = 0.021), compared to controls. ATGL was upregulated in gastric cancer vs controls (p = 0.014) and higher HSL was found in gastric (p = 0.008) and in pancreatic cancer (p = 0.033) vs controls. At the protein level, we found higher CGI-58 in cancer vs controls (p = 0.019) and in cachectic vs controls (p = 0.029), as well as in gastric cancer vs controls (p = 0.027). In our cohort of GI cancer patients, we found a modulation in the expression of genes and proteins involved in lipolysis, and differences were interestingly detected according to cancer type.","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"103 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139079941","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}

{"title":"A feedback loop of PPP and PI3K/AKT signal pathway drives regorafenib-resistance in HCC","authors":"Huihua Yang, Dahong Chen, Yafei Wu, Heming Zhou, Wenjing Diao, Gaolin Liu, Qin Li","doi":"10.1186/s40170-023-00311-5","DOIUrl":"https://doi.org/10.1186/s40170-023-00311-5","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a principal type of liver cancer with high incidence and mortality rates. Regorafenib is a novel oral multikinase inhibitor for second-line therapy for advanced HCC. However, resistance to regorafenib is gradually becoming a dilemma for HCC and the mechanism remains unclear. In this study, we aimed to reveal the metabolic profiles of regorafenib-resistant cells and the key role and mechanism of the most relevant metabolic pathway in regorafenib resistance. Metabolomics was performed to detect the metabolic alteration between drug-sensitive and regorafenib-resistant cells. Colony formation assay, CCK-8 assay and flow cytometry were applied to observe cell colony formation, cell proliferation and apoptosis, respectively. The protein and mRNA levels were detected by western blot and RT-qPCR. Cell lines of Glucose-6-phosphate dehydrogenase(G6PD) knockdown in regorafenib-resistant cells or G6PD overexpression in HCC cell lines were stably established by lentivirus infection technique. G6PD activity, NADPH level, NADPH/NADP+ ratio, the ratio of ROS positive cells, GSH level, and GSH/GSSG ratio were detected to evaluate the anti-oxidative stress ability of cells. Phosphorylation levels of NADK were evaluated by immunoprecipitation. Metabonomics analysis revealed that pentose phosphate pathway (PPP) was the most relevant metabolic pathway in regorafenib resistance in HCC. Compared with drug-sensitive cells, G6PD enzyme activity, NADPH level and NADPH/NADP+ ratio were increased in regorafenib-resistant cells, but the ratio of ROS positive cells and the apoptosis rate under the conditions of oxidative stress were decreased. Furthermore, G6PD suppression using shRNA or an inhibitor, sensitized regorafenib-resistant cells to regorafenib. In contrast, G6PD overexpression blunted the effects of regorafenib to drug-sensitive cells. Mechanistically, G6PD, the rate-limiting enzyme of PPP, regulated the PI3K/AKT activation. Furthermore, PI3K/AKT inhibition decreased G6PD protein expression, G6PD enzymatic activity and the capacity of PPP to anti-oxidative stress possibly by inhibited the expression and phosphorylation of NADK. Taken together, a feedback loop of PPP and PI3K/AKT signal pathway drives regorafenib-resistance in HCC and targeting the feedback loop could be a promising approach to overcome drug resistance.","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"6 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138715218","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}

{"title":"STEAP4 inhibits cisplatin-induced chemotherapy resistance through suppressing PI3K/AKT in hepatocellular carcinoma","authors":"Binhui Xie, Baiyin Zhong, Zhenxian Zhao, Jie Hu, Jianqiong Yang, Yuankang Xie, Jianhong Zhang, Jianting Long, Xuewei Yang, Heping Li","doi":"10.1186/s40170-023-00323-1","DOIUrl":"https://doi.org/10.1186/s40170-023-00323-1","url":null,"abstract":"Chemotherapy resistance is the leading cause for hepatocellular carcinoma (HCC)-induced death. Exploring resistance generation mechanism is an urgent need for HCC therapy. Here, we found STEAP4 was significantly downregulated in HCC patients with recurrence. Patients with low STEAP4 had poor outcome, suggesting STEAP4 might inhibit chemotherapy resistance. Cell viability assay, colony formation assay, apoptosis assay, soft agar growth assay, and tumor animal model showed STEAP4 inhibited cisplatin resistance. Mechanism analysis showed STEAP4 inhibited PI3K/AKT pathway through directly interacting with AKT. Double knockdown of STEP4 and AKT significantly inhibited cisplatin resistance. We also found STEAP4 expression was negatively correlated with PI3K/AKT pathway activity in clinic specimens. In summary, our findings suggested STEAP4 inhibited cisplatin resistance through suppressing PI3K/AKT pathway activity, providing a target for HCC therapy. ","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"37 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138715006","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}

{"title":"A HIF-1α inhibitor combined with palmitic acid and L-carnitine treatment can prevent the fat metabolic reprogramming under hypoxia and induce apoptosis in hepatocellular carcinoma cells","authors":"Shohei Matsufuji, Yoshihiko Kitajima, Kazuki Higure, Naoya Kimura, Sachiko Maeda, Kohei Yamada, Kotaro Ito, Tomokazu Tanaka, Keita Kai, Hirokazu Noshiro","doi":"10.1186/s40170-023-00328-w","DOIUrl":"https://doi.org/10.1186/s40170-023-00328-w","url":null,"abstract":"A hypoxic environment often persists within solid tumors, including hepatocellular carcinoma (HCC). Hypoxia-inducible factor-1α (HIF-1α) can accelerate cancer malignancy by inducing hypoxia-dependent expression of various genes. Tumor hypoxia can also induce metabolic reprogramming of fatty acid (FA) metabolism, through which HIF-1α plays an essential role in diminishing fatty acid β-oxidation (FAO) in hypoxic cancer cells. We aimed to investigate potential new drug therapy options for targeting hypoxic cancer cells within HCC tumors, specifically through combining HIF-1α inhibition with palmitic acid (PA) + L-carnitine (LC) treatment to effectively induce apoptosis in hypoxic HCC cells. To test this hypothesis, in vitro and in vivo studies were performed. We first demonstrated that hypoxia-dependent apoptosis was induced by an overload of PA in two HCC cell lines (HepG2 and Hep3B) via excessive production of reactive oxygen species (ROS). Moreover, this observed PA-induced apoptosis was enhanced by HIF-1α knockdown (KD) in these cells under hypoxia. In addition, the combination of PA with FAO activator LC increased FAO activity and led to stronger cell death than PA alone in hypoxic HIF-1α KD cells, specifically through further ROS generation. To clarify the mechanism of hypoxia-induced FA metabolism reprogramming, expression levels of the genes encoding FAO enzymes CPT1A, ACSL1, MCAD, and LCAD, FA transporter CD36, and FA esterification enzymes DGAT and APGAT were analyzed using HIF-1α KD and scramble control (SC) cells. The results suggested that HIF-1α could repress mRNA expression of the FAO-related enzymes and CD36, while it upregulated FA esterification gene expression. This suggested a central role for HIF-1α in hypoxia-induced reprogramming of FA metabolism in HCC cells. Using a nude mouse model, PA administration was found to induce apoptosis from ROS overproduction in HIF-1α KD tumors compared with SC tumors. Additional LC treatment synergistically enhanced the PA-induced apoptosis in HIF-1α KD tumors. Finally, in vivo therapy composed of HIF-1α inhibitor YC-1 with PA + LC could induce ROS-mediated apoptosis in HepG2 tumors without significant toxicity. A combination therapy of YC-1 with PA + LC may be a unique anti-tumor therapy for targeting hypoxic HCC cells, specifically by ROS overproduction leading to forced FAO activation.","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"21 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138561473","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}

{"title":"The classification of obesity based on metabolic status redefines the readmission of non-Hodgkin's lymphoma-an observational study.","authors":"Hang Dong, Honglin Guo, Jing Du, Yiping Cheng, Dawei Wang, Junming Han, Zinuo Yuan, Zhenyu Yao, Ran An, Xiaoqin Wu, Kyle L Poulsen, Zhixiang Wang, Shanshan Shao, Xiude Fan, Zhen Wang, Jiajun Zhao","doi":"10.1186/s40170-023-00327-x","DOIUrl":"10.1186/s40170-023-00327-x","url":null,"abstract":"<p><strong>Background: </strong>The relationship between obesity and non-Hodgkin's lymphoma (NHL) was controversial, which may be due to the crudeness definition of obesity based on body mass index (BMI). As obesity and metabolic abnormalities often coexist, we aimed to explore whether the classification of obesity based on metabolic status can help to evaluate the real impact of obesity on the readmission of NHL.</p><p><strong>Methods: </strong>In this retrospective cohort study, utilizing the 2018 Nationwide Readmissions Database, we identified NHL-related index hospitalizations and followed them for non-elective readmission. The patients with NHL were classified as metabolically healthy non-obese (MHNO) and obese (MHO) and metabolically unhealthy non-obese (MUNO) and obese (MUO). Readmission rates for each phenotype were calculated at 30-day intervals. Multiple COX regression was used to analyze the association of metabolic-defined obesity with 30-day, 90-day, and 180-day readmission rates in patients with NHL.</p><p><strong>Results: </strong>There were 22,086 index hospitalizations with NHL included. In the multivariate COX regression, MUNO was associated with increased 30-day (HR = 1.113, 95% CI 1.036-1.195), 90-day (HR = 1.148, 95% CI 1.087-1.213), and 180-day readmission rates (HR = 1.132, 95% CI 1.077-1.189), and MUO was associated with increased 30-day (HR=1.219, 95% CI: 1.081-1.374), 90-day (HR = 1.228, 95% CI 1.118-1.348), and 180-day readmission rates (HR = 1.223, 95% CI 1.124-1.33), while MHO had no associations with readmission rates.</p><p><strong>Conclusions: </strong>The presence of metabolic abnormalities with or without obesity increased the risk of non-selective readmission in patients with NHL. However, obesity alone had no associations with the risk of non-selective readmission, suggesting that interventions for metabolic abnormalities may be more important in reducing readmissions of NHL patients.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"11 1","pages":"24"},"PeriodicalIF":5.9,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10698918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497922","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}

{"title":"Metabolic changes preceding bladder cancer occurrence among Korean men: a nested case-control study from the KCPS-II cohort.","authors":"Youngmin Han, Unchong Kim, Keum Ji Jung, Ji-Young Lee, Kwangbae Lee, Sang Yop Shin, Heejin Kimm, Sun Ha Jee","doi":"10.1186/s40170-023-00324-0","DOIUrl":"10.1186/s40170-023-00324-0","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BLCA) research in Koreans is still lacking, especially in focusing on the prediction of BLCA. The current study aimed to discover metabolic signatures related to BLCA onset and confirm its potential as a biomarker.</p><p><strong>Methods: </strong>We designed two nested case-control studies using Korean Cancer Prevention Study (KCPS)-II. Only males aged 35-69 were randomly selected and divided into two sets by recruitment organizations [set 1, BLCA (n = 35) vs. control (n = 35); set 2, BLCA (n = 31) vs. control (n = 31)]. Baseline serum samples were analyzed by non-targeted metabolomics profiling, and OPLS-DA and network analysis were performed. Calculated genetic risk score (GRS) for BLCA from all KCPS participants was utilized for interpreting metabolomics data.</p><p><strong>Results: </strong>Critical metabolic signatures shown in the BLCA group were dysregulation of lysine metabolism and tryptophan-indole metabolism. Furthermore, the prediction model consisting of metabolites (lysine, tryptophan, indole, indoleacrylic acid, and indoleacetaldehyde) reflecting these metabolic signatures showed mighty BLCA predictive power (AUC: 0.959 [0.929-0.989]). The results of metabolic differences between GRS-high and GRS-low groups in BLCA indicated that the pathogenesis of BLCA is associated with a genetic predisposition. Besides, the predictive ability for BLCA on the model using GRS and five significant metabolites was powerful (AUC: 0.990 [0.980-1.000]).</p><p><strong>Conclusion: </strong>Metabolic signatures shown in the present research may be closely associated with BLCA pathogenesis. Metabolites involved in these could be predictive biomarkers for BLCA. It could be utilized for early diagnosis, prognostic diagnosis, and therapeutic targets for BLCA.</p>","PeriodicalId":9418,"journal":{"name":"Cancer & Metabolism","volume":"11 1","pages":"23"},"PeriodicalIF":5.9,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486722","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}