RESUMO
BACKGROUND: The prognostic value of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) has been extensively studied and verified by the CellSearch® system. Varieties of microfluidic systems have been developed to improve capture efficiency with the lack of standardization and automation. This study systematically verified the positive threshold for prognosis and its guidance value in anti-HER2 therapy based on a novel automated microfluidic system OmiCell®. METHODS: CTCs isolation, enumeration and labeling were performed using the OmiCell® system. CTCs identification and reporting were performed using the DeepSight® scanning system. RESULTS: The capture efficiency and specificity of OmiCell® system was 91.9% and 90%, respectively. Then, 65 MBC patients with known HER2 status of their metastatic tumors were enrolled. In the cohort, we detected ≥ 1 CTCs in 59 patients (90.8%, range: 1-55 CTCs, median = 6), < 8 CTCs in 45 (69.2%) and ≥ 8 CTCs in 20 (30.8%) patients at baseline. The patients with < 8 CTCs had longer PFS than ≥ 8 CTCs (median, 7 vs. 4.4 months, p = 0.028). CTC enumeration was found to be an independent prognostic factor in our cohort. Moreover, we found a weak concordance between tissue HER2 (tHER2) status and the corresponding CTCs (k = 0.16, p = 0.266). The patients with tHER2 positive and cHER2 negative had better PFS compared with patients with both tHER2 and cHER2 positive (median, 8.2 vs. 3.3 months, p = 0.022). CONCLUSIONS: This clinical study shows the prognosis value of a new threshold of CTC number and meanwhile the guidance value of cHER2 status in anti-HER2 therapy.
Assuntos
Neoplasias da Mama , Células Neoplásicas Circulantes , Receptor ErbB-2 , Humanos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Receptor ErbB-2/metabolismo , Prognóstico , Pessoa de Meia-Idade , Idoso , Adulto , Biomarcadores Tumorais/metabolismo , Metástase Neoplásica , Contagem de Células , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Idoso de 80 Anos ou mais , Microfluídica/métodosRESUMO
BACKGROUND: During immunotherapy treatment and survival, identifying symptoms requires a standardized and validated assessment tool. The aim of this study was to translate, validate and use the Chinese version of the Immunotherapy of the M.D. Anderson Symptom Inventory for Early-Phase Trials module (MDASI-Immunotherapy EPT) to assess the symptom burden of cancer patients receiving immunotherapy in China. METHODS: The MDASI-Immunotherapy EPT was translated into Chinese using Brislin's translation model and the back-translation method. In total, 312 Chinese-speaking colorectal cancer patients receiving immunotherapy were enrolled in the trial from August 2021 to July 2022 after receiving definitive diagnoses in our cancer center. The reliability and validity of the translated version was evaluated. RESULTS: Cronbach's α values were 0.964 and 0.935 for the symptom severity and interference scales, respectively. Significant correlations were found between the MDASI-Immunotherapy EPT-C and FACT-G scores (-0.617-0.732, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by ECOG PS (all P < 0.01). The overall mean subscale scores for the core and interference subscales were 1.92 ± 1.75 and 1.46 ± 1.87, respectively. Fatigue, numbness/tingling, and disturbed sleep had the highest scores for the most serious symptoms. CONCLUSION: The MDASI-Immunotherapy EPT-C showed adequate reliability and validity for measuring symptoms among Chinese-speaking colorectal cancer patients receiving immunotherapy. The tool could be used in clinical practice and clinical trials to gather patients' health and quality of life data and manage their symptoms in a timely manner in the future.
RESUMO
BACKGROUND: Little is known about patients' intention for participation in end-of-life decisions (EOLD) in three coastal provinces in southern China. This study aimed to explore the willingness of patients with cancer pain to participate in EOLD and potential influencing factors. METHODS: A multi-center cross-sectional study was performed in three coastal provinces in southern China. Two hundred and thirty patients with cancer pain were recruited and consented to fill out the questionnaires. The patients' willingness to participate in EOLD, demographic and disease-related data was surveyed. RESULTS: In total, 223 patients completed and returned the survey (response rate = 96.95%). One hundred four cases (46.64%) were willing to participate in EOLD. 119 (54.36%) cases not willing to participate in EOLD, respectively. Multivariate logistic regression analysis shows that educational level (OR: 0.683, 95% CI: 0.482-0.966), history of alcoholism (OR: 8.353, 95%CI: 2.535-27.525), Eastern Cooperative Oncology Group (ECOG) score (OR: 0.645, 95% CI: 0.450-0.925) and experience of explosive pain (OR: 6.367, 95% CI: 3.103-13.062) and clinical rescue (OR: 3.844, 95% CI: 1.722-8.577) had significant effects on EOLD intention (P < 0.05). Finally, a predictive model combined above five factors was established, which showed a good discrimination (area under receiver operating characteristic curve: 0.849, 95% CI: 0.796-0.899, P < 0.001) and calibration (Hosmer-Lemeshow Test: Chi-square = 10.103, P = 0.258) for which patients more willing to participate in EOLD. CONCLUSIONS: The willingness of patients with cancer pain to participate in EOLD is at a modest level in three coastal provinces in southern China. Patients with lower educational level, history of alcoholism, better health status and experience of explosive pain and clinical rescue may be more prone to participate in EOLD.
Assuntos
Alcoolismo , Dor do Câncer , Neoplasias , Humanos , Estudos Transversais , Neoplasias/complicações , China , Dor , MorteRESUMO
BACKGROUND: Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC). METHODS: In the dose-escalation phase, patients received AA (0.2-1.5 g/kg, 3-h infusion, once daily, days 1-3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed. RESULTS: Thirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1-3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3-4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF. CONCLUSIONS: The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT02969681 .
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácido Ascórbico/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , Povo Asiático , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Totally implantable access port (TIAP) is a subcutaneously implanted, long-term infusion device that is widely used in oncology patients. However, multiple needle insertions into TIAP may lead to pain, anxiety, and dread in patients. This study aimed to compare the effectiveness of Valsalva maneuver, eutectic mixture of local anesthetics (EMLA) cream, and the combination of both in relieving pain of cannulations on TIAP. METHODS: This was a prospective randomized controlled study. We included 223 patients treated with antineoplastic drugs and randomized them into four groups: EMLA Group (Group E), control Group (Group C), Valsalva maneuver Group (Group V), and EMLA cream combing with Valsalva maneuver Group (Group EV). Each group was given the corresponding intervention before non-coring needle insertion. The data on pain scores and overall comfort were collected by numerical pain rating scale (NPRS) and visual analog scale (VAS). RESULTS: Group E and Group EV experienced the least amount of pain scores in needle insertion, which was significantly lower than Group V and Group C (p < 0.05). Meanwhile, Group E and Group EV obtained the highest comfort level, which was significantly higher than group C (p < 0.05). Fifteen patients developed localized skin erythema after the application of medical Vaseline or EMLA cream and subsided within half an hour after rubbing. CONCLUSION: EMLA cream is a safe and effective way to alleviate pain during non-coring needle insertion in TIAP and enhance the overall comfort of patients. We recommend applying EMLA cream 1 h before needle insertion of TIAP, especially in patients having needle phobia or high pain scores from previous non-coring needle insertion.
RESUMO
PURPOSE: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. RESULTS: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. CONCLUSIONS: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.
Assuntos
Antineoplásicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácido Ascórbico/efeitos adversos , Bevacizumab , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila , Glucosefosfato Desidrogenase/uso terapêutico , Humanos , Leucovorina , Neoplasias Retais/etiologiaRESUMO
BACKGROUND: Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin-based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin-induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy. METHODS: In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI-CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity (NCI-CTCAE or the oxaliplatin-specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3-year disease-free survival (DFS) and adverse events. RESULTS: There were no significant differences between the arms in the rate of NCI-CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ-CIPN20 or time to grade 2 neurotoxicity using NCI-CTCAE and the oxaliplatin-specific neuropathy scale. GM1 substantially decreased participant-reported acute neurotoxicity (sensitivity to cold items [P < .01], discomfort swallowing cold liquids [P < .01], throat discomfort [P < .01], muscle cramps [P < .01]). The rates of dose reduction or withdrawal were not significantly different between the arms (P = .08). The 3-year DFS rates were 85% and 83% in the GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms. CONCLUSION: Patients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. (ClinicalTrials.gov number, NCT02251977).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Gangliosídeo G(M1)/administração & dosagem , Oxaliplatina/efeitos adversos , Oxaloacetatos/efeitos adversos , Doenças do Sistema Nervoso Periférico/epidemiologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaloacetatos/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/prevenção & controle , Placebos/administração & dosagem , Índice de Gravidade de DoençaRESUMO
The hematogenous metastatic pattern of gastric cancer (GC) was not fully explored. Here we analyzed the frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from GC patients. Data queried for this analysis included GC patients from the Surveillance, Epidemiology, and End Results Program database from 2010 to 2014. All of statistical analyses were performed using the Intercooled Stata 13.0 (Stata Corporation, College Station, TX). All statistical tests were two-sided. Totally, there were 19 022 eligible patients for analysis. At the time of diagnosis, there were 7792 patients at stage IV, including 3218 (41.30%) patients with liver metastasis, 1126 (14.45%) with lung metastasis, 966 (12.40%) with bone metastasis and 151 (1.94%) with brain metastasis. GC patients with lung or liver metastasis have a higher risk of bone and brain metastasis than those without lung nor liver metastasis. Intestinal subtype had significantly higher rate of liver and lung metastasis, while diffuse type was more likely to have bone metastasis. Proximal stomach had significantly higher risk to develop metastasis than distal stomach. African-Americans had the highest risk of liver metastasis and Caucasian had the highest prone to develop lung and brain metastasis. The median survival for patients with liver, lung, bone, and brain metastasis was 4 months, 3 months, 4 months and 3 months, respectively. It is important to evaluate the status of bone and brain metastasis in GC patients with lung or liver metastasis. Knowledge of metastatic patterns is helpful for clinicians to design personalized pretreatment imaging evaluation for GC patients.
Assuntos
Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/secundário , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/secundário , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/história , Neoplasias Encefálicas/história , Feminino , História do Século XXI , Humanos , Neoplasias Hepáticas/história , Neoplasias Pulmonares/história , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Programa de SEER , Fatores Socioeconômicos , Neoplasias Gástricas/história , Estados Unidos/epidemiologiaRESUMO
Nasopharyngeal carcinoma (NPC), which originates from the nasopharynx, is highly prevalent in Southern China and Southeast Asia, and more than 90% of all NPCs are non-keratinizing undifferentiated cells or poorly differentiated squamous cells. Cancer stem cells (CSCs) are capable of self-renewal and have differentiation potential. These properties form the basis of cancer initiation, development, and radiochemoresistance. However, the molecular mechanisms underlying NPC CSC maintenance remain poorly understood. Here, genomic expression profiling using our previously established monoclonal cellular and animal models revealed that interferon regulatory factor 6 (IRF6) was downregulated in highly metastatic NPC cells, cancer stem-like NPC cells and animal models. Functional assays revealed that elevated IRF6 expression suppressed cell proliferation, growth, CSCs properties and enhanced cell chemotherapeutic sensitivity. However, silencing IRF6 resulted in opposing effects. Moreover, we determined that as a tumor suppressor gene and transcription factor, IRF6 directly bound the upstream region of the ATP-binding cassette sub-family G member 2 (ABCG2) DNA element and suppressed target ABCG2 expression in NPC cells. Consistently, an inverse correlation was observed between the mRNA levels of IRF6 and ABCG2 in clinical NPC samples. With these results, we provide the first evidence that IRF6 directly targets the ABCG2 gene and selectively kills CSCs in NPC and that IRF6 may be a valuable tool for developing new CSC-targeted treatment strategies for undifferentiated NPC patients.
Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Células-Tronco Neoplásicas/patologia , Fenótipo , RNA Interferente Pequeno/metabolismoRESUMO
Recruitment rate of clinical trials in cancer patients is pretty low in China. Little is known about factors influencing trial recruitment in Chinese cancer patients. The aim of present study is to evaluate the barriers and facilitators to participation in clinical trials among lymphoma patients in China.From December 2014 to August 2015, the survey was carried out in the Department of Medical Oncology in Sun Yat-sen University Cancer Center. A self-made questionnaire was used among lymphoma patients (Nâ=â331) to evaluate their attitude toward clinical trials. The questionnaire included 2 parts: patients' basic information and whether they were willing to participate in future clinical trials and their reasons.There were 53.5% patients willing to participate in clinical trials. The most common reasons were thirst for new treatments, trust on hospital and doctors, the idea that clinical trials may be more effective than conventional therapy, and to get more management and monitoring. The following patients are more likely to participate in clinical trials: patients who have children (Pâ=â.019) or spouse (Pâ=â.037), cannot afford treatment cost (Pâ=â.019), have tumor relapse (Pâ=â.045), and cared about the medical development (Pâ=â.032). Patients who have little knowledge of clinical trials are less likely to participate in clinical trials (Pâ=â.047).Popularization of knowledge about clinical trial is helpful to improve clinical trial participation in Chinese lymphoma patients.
Assuntos
Ensaios Clínicos como Assunto , Linfoma/terapia , Participação do Paciente , Centros Médicos Acadêmicos , Adulto , China , Família , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Linfoma/economia , Linfoma/epidemiologia , Linfoma/psicologia , Masculino , Pessoa de Meia-Idade , Participação do Paciente/economia , Participação do Paciente/psicologia , Seleção de Pacientes , Recidiva , Inquéritos e Questionários , ConfiançaRESUMO
Trastuzumab has substantial antitumor activity in metastatic gastric cancer. One such mechanism by which it exerts its antitumor activity is antibody-dependent cell-mediated cytotoxicity, which has been reported to be influenced by FcγRIIA and IIIA polymorphisms. This study is the first to assess their impact on trastuzumab efficacy in patients with metastatic gastric cancer. We retrospectively examined 42 Her-2-positive patients receiving fluorouracil and platinum-based chemotherapy and trastuzumab, and 68 Her-2-negative patients receiving fluorouracil and platinum-based chemotherapy only as the first-line treatment. FcγRIIA and IIIA polymorphisms were assessed, and their associations with efficacy in both settings were analyzed. In patients treated with trastuzumab, the FcγRIIA H/H genotype was associated with significantly superior progression-free survival (PFS) (hazard ratio [HR] [95% CI]: 0.36 [0.16-0.82], adjusted HR [95% CI]: 0.18 [0.07-0.48], P=0.001). When combining FcγRIIA and IIIA polymorphisms, the FcγRIIA H/H or FcγRIIIA V/V genotype was associated with a significantly improved disease control rate (P=0.04) and PFS (HR [95% CI]: 0.29 [0.13-0.67], adjusted HR [95% CI]: 0.17 [0.07-0.45], P<0.001). As expected, no association of FcγRIIA and IIIA polymorphisms with efficacy was found in patients receiving chemotherapy only. We concluded that FcγRIIA and IIIA polymorphisms might predict disease control rate and PFS in metastatic gastric cancer patients receiving trastuzumab treatment.
RESUMO
Purpose: Patients with advanced or metastatic adenocarcinoma of the stomach or esophagogastric junction for whom trastuzumab therapy is being considered, assessment for tumor human epidermal growth factor receptor-2 (HER2) status is necessary. Can the HER2 status and Lauren classification of the biopsy sample truly represent the HER2 status in the gastric cancer? Methods: Formalin-fixed, paraffin-embedded sections of 116 pair surgically resected and biopsy specimens as well as 80 pair primary and metastatic lesions of gastric cancer patients were analyzed. Protein expression was assessed using immunohistochemistry (IHC) and graded by the modified scoring criteria for gastric cancer. Gene amplification was evaluated by fluorescence in situ hybridization (FISH) in IHC 2+ cases. Results: The positive rate of HER2 was 11.2% in both surgical and biopsy samples. The consistent rate of HER2 expression was 91.4% (106/116) between biopsy and surgical samples, P=0.666. The positive rate of HER2 was 20.5% in primary and 15.9% in metastatic samples, P=0.1876. The consistent rate of HER2 expression was 90.9% (40/44) between primary and metastatic samples, P=0.580. The consistent rate of Lauren classification was 64.7% (75/116) between biopsy and surgical sample, and 92.5% (74/80) between primary and metastatic samples. Discussion: For gastric cancer, HER2 expression and Lauren classification were highly homogenous in biopsy and surgical samples, primary and their corresponding metastatic samples. The high concordance observed between these two cohorts indicated that the HER2 examination and Lauren classification of biopsy samples from the primary tumor could well represent the metastatic lesions of the patients.
RESUMO
Serglycin is a proteoglycan that was first found to be secreted by hematopoietic cells. As an extracellular matrix (ECM) component, serglycin promotes nasopharyngeal carcinoma (NPC) metastasis and serves as an independent, unfavorable NPC prognostic indicator. The detailed mechanism underlying the roles of serglycin in cancer progression remains to be clarified. Here, we report that serglycin knockdown in NPC cells inhibited cell sphere formation and tumor seeding abilities. Serglycin downregulation enhanced high-metastasis NPC cell sensitivity to chemotherapy. It has been reported that serglycin is a novel ligand for the stem cell marker CD44. Interestingly, we found a positive correlation between serglycin expression and CD44 in nasopharyngeal tissues and NPC cell lines. Further study revealed that CD44 was an ERK-dependent downstream effector of serglycin signaling, and serglycin activated the MAPK/ß-catenin axis to induce CD44 receptor expression in a positive feedback loop. Taken together, our novel findings suggest that ECM serglycin upregulated CD44 receptor expression to maintain NPC stemness by interacting with CD44 and activating the MAPK/ß-catenin pathway, resulting in NPC cell chemoresistance. These findings suggest that the intervention of serglycin/CD44 axis and downstream signaling pathway is a rational strategy for targeting NPC cancer stem cell therapy.