Decreased survival in cervical cancer patients with thromboembolic events

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16034-16034
Author(s):  
G. M. Jacobson ◽  
M. Goodheart ◽  
B. Smith ◽  
J. Lammli
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Gynecologic Oncology ◽  
Retrospective Chart Review ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
P Value ◽  
Thromboembolic Events ◽  
The University

16034 Background: We have previously reported on the incidence of thromboembolic events (TE) in cervical cancer patients treated with definitive chemoradiation.Patients with TE seemed to have decreased survival compared to those without TE. We reviewed a larger cohort to compare the survival of cervical cancer patients with and without TE. Materials and Methods: We performed a retrospective chart review of cervical cancer patients diagnosed and treated at the University for Iowa from January 1997 until December 2003. Data sources included the University of Iowa Tumor Registry, the Gynecologic Oncology Tumor Data Base, and the relevant ICD-9 codes to identify cervical carcinoma and types of TE in both inpatients and outpatients. Statistical analysis included the Pearson chi-squared test for categorical variable, and the two-sample t-test for continuous factors. Log-rank tests were used for survival analysis along with the generation of Kaplan-Meier survival curves. Multivariate analysis was performed with Cox proportional hazards regression. All tests are two sided and carried out at the 5% level of significance. Results: Three hundred and fifty nine (359) patients were treated with surgery or chemoradiation; thirty-six patients (10%) developed TE. There were significant associations between thromboembolic status and pelvic irradiation (p=0.0493), chemotherapy (p=0.0118), and stage (p=0.0197). Survival could not be estimated for patients not experiencing a thromboembolism; survival did not drop below 50% by the end of follow-up. Median survival time for patients with thromboembolism was 4.5 years. According to log-rank test, this difference was significant (p-value<0.0001). Conclusion: The incidence of thromboembolic events in this cohort of cervical cancer patients was 10%. TE was associated with a significant decrease in survival. No significant financial relationships to disclose.

scholarly journals Survival Analysis and Prognostic Predictor Study of Colorectal Cancer Patients with Single-Site Metastasis

2021 ◽  
pp. 1-18
Author(s):  
Jaydutt V. Vadgama ◽  
Wenhong Deng ◽  
Katrina M Schrode ◽  
Magda Shaheen ◽  
Jaydutt V. Vadgama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Proportional Hazards ◽  
Regional Lymph Node ◽  
Measurement Data ◽  
Gene Mutations ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
P Value ◽  
Term Survival

Metastatic colorectal cancer (mCRC) patients have various metastasis patterns, which reflect diverse biological characteristics of different patient subgroups. We analyse the prognosis of mCRC patients according to the metastatic site and clarify the relationship between tumor or patient characteristics and the metastatic sites. The whole sequencing and clinical data of 2329 CRC patients were obtained from TCGA and a database of the MSKCC. Kruskal Wallis Tests were used to analyse measurement data. Survival was illustrated by Kaplan-Meier curves, with P value determined by Log-rank Test. Hazard’s ratio was determined through the univariate and multivariate COX proportional hazards regression model. The mortality rate of CRC patients with liver-only metastasis (mCRC-liver) did not increase versus nonmetastatic patients. The survival rate of patients with non-regional lymph node-only metastasis (mCRCNRLN) was lower versus mCRC-liver. Mutations of KRAS and TCF7L2 genes were associated with mortality of mCRC-liver. APC mutation was associated with reduced mortality in mCRC-lung and mCRCNRLN. BRAF mutation was associated with increased mortality of mCRC-peritoneum. In a multivariate COX analysis, gender affected the survival rate of mCRC-liver. Age and the number of gene mutations affected the survival rate of mCRC-lung and mCRC-NRLN respectively. Receiving chemotherapy is an unfavourable factor for prognosis of mCRC-liver, but the length of chemotherapy treatment is an advantageous prognosis factor. This study depicts the long-term survival features of a group of mCRC patients. These findings promoted our understanding of the prognosis characteristics of CRC and have positive guiding significance for clinical management of CRC patients.

Early carcinoembryonic antigen (CEA) dynamics to predict fruquintinib efficacy in FRESCO, a 3+ line metastatic colorectal carcinoma (mCRC) phase III trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16001-e16001
Author(s):  
Yuxian Bai ◽  
Shukui Qin ◽  
Jin Li ◽  
Yanhong Deng ◽  
Lei Yang ◽  
...  
Keyword(s):  
Placebo Group ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Rank Test ◽  
P Value ◽  
Radiological Evaluation

e16001 Background: The FRESCO phase 3 trial demonstrated a significant survival benefit with fruquintinib vs. placebo in the third-line or later therapy of mCRC patients. CEA levels are widely used in conjunction with imaging to monitor response to systemic therapy in patients with mCRC. Herein, we undertook post-hoc analyses of FRESCO patient data to investigate the early changes in CEA during treatment, as well as potential relationships with efficacy parameters. Methods: Patients were included if baseline CEA was abnormal according to local lab reference range. Serum CEA levels were measured at baseline and Day 1 of each cycle (except for Cycle 1). Early CEA change was analyzed at first radiological evaluation (C3D1, Week 8), CEA response was defined as ≥ 50% decrease from baseline, and CEA progression was defined as ≥ 100% increase from baseline. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated through Cox proportional hazards model; p-value was generated from log rank test. Results: 88.4% (245/277) and 94.9% (130/137) of patients had an abnormal baseline CEA in the fruquintinib group and placebo group, respectively. Median baseline CEA values were similar between treatment groups. After 2 cycles of treatment, the proportion of patients had CEA response was significantly higher in the fruquintinib group than placebo group (30.0% vs. 1.3%, p < 0.001). In the fruquintinib group, patients with early CEA response (n = 63) had longer median OS (12.8 vs. 7.8 months, HR = 0.45, p < 0.001) and median PFS (5.6 vs. 3.7 months, HR = 0.49, p < 0.001) than patients without (n = 147). 66.7% (140/210) of patients in fruquintinib group had stable disease (SD), and fruquintinib in those patients with concomitant CEA response exhibited a significantly greater OS benefit than with CEA progression (14.4 vs. 8.7 months, HR = 0.38, p = 0.004). Conclusions: Fruquintinib increased early CEA response. CEA response at first radiological evaluation after cycle 2 could be considered as a predictor for better OS and PFS. Among patients with SD at first evaluation, those with CEA response seems benefit more from fruquintinib. Clinical trial information: NCT02314819 .

scholarly journals Serum Tie-1 is a Valuable Marker for Predicting the Progression and Prognosis of Cervical Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Rui Bai ◽  
Bowen Diao ◽  
Kaili Li ◽  
Xiaohan Xu ◽  
Ping Yang
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Tumor Stage ◽  
Healthy Controls ◽  
Cervical Lesions ◽  
Advanced Tumor ◽  
Valuable Marker

Objective: To investigate whether serum Tie-1 (sTie-1) is a valuable marker for predicting progression and prognosis of cervical cancer.Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sTie-1 concentrations in 75 cervical cancer patients, 40 cervical intraepithelial neoplasia (CIN) patients, and 55 healthy controls without cervical lesions, and sTie-1 levels were compared between the groups. Receiver operating characteristic curves was used to evaluate the diagnostic value of sTie-1. The relationship between sTie-1 concentrations in patients with cervical cancer and clinicopathological features and prognosis were analyzed, and the risk factors for postoperative recurrence were determined using univariate and multivariable Cox proportional hazards regression.Results: We found that sTie-1 concentrations gradually increased according to lesion severity (i.e., cancer vs. CIN; p &lt; 0.05) and were significantly elevated in adenocarcinoma compared with healthy controls. sTie-1 levels strongly distinguished between cervical cancer patients and the healthy controls (area under the curve = 0.846; cut-off value = 1,882.64 pg/ml; sensitivity = 74.6%; specificity = 96.4%). Moreover, sTie-1 levels in cervical cancer patients were significantly associated with tumor size, advanced tumor stage, lymph node metastasis, and reduced 4-years progression-free survival. Cervical cancer patients with high sTie-1 concentrations had a 3.123-fold [95% confidence interval (CI): 1.087–8.971, p = 0.034] higher risk for tumor recurrence.Conclusions: Elevated sTie-1 levels in patients with cervical carcinoma were associated with tumor progression and poor prognosis, indicating that sTie-1 may be a valuable marker for predicting progression and prognosis of cervical cancer.

Impact of age at diagnosis on survival of hormone-refractory prostate cancer (HRPC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16050-e16050
Author(s):  
M. R. Humphreys ◽  
C. Ma ◽  
S. S. Sridhar
Keyword(s):  
Multivariate Analysis ◽  
Bone Metastasis ◽  
Proportional Hazards ◽  
Survival Curve ◽  
Performance Status ◽  
Retrospective Chart Review ◽  
Cox Proportional Hazards ◽  
Age At Diagnosis ◽  
Rank Test ◽  
Androgen Ablation

e16050 Background: Conflicting data exist for age as a determinant of overall survival (OS) in pts with HRPC. We hypothesize that young (<55) HRPC pts represent a more aggressive biological phenotype and therefore have a decreased OS. Methods: A retrospective chart review was conducted on 334 consective HRPC pts treated between 1995–2005. Summary statistics for demographic and clinical factors were generated, and Kaplan-Meier (KM) OS curves were created. Bivariate Cox Proportional-Hazards regression was used to test the association of age at diagnosis while adjusting for a covariate, with significant covariates entered into multivariate models. Results: Overall median survivals in the age stratified categories (<55, ≥55–65, ≥65–75, ≥75) were 5.5, 6.9, 7.9, and 4.3 yrs, with 5 yr survivals 51.9%, 67.4%, 67.0%, and 34.9%, respectively. KM curves showed divergence with an overall significant log-rank test (p < 0.0001). Compared to pts ≥65–75, the hazard ratios (HR) for HRPC pts <55 and ≥75 were 1.40 (95% CI 0.90–2.60) and 2.52 (95% CI 1.67–3.82), respectively. However, following multivariate analysis HRs for HRPC pts <55 and ≥75 were 1.60 (95% CI 0.98–2.62) and 1.25 (95% CI 0.71–2.20). Pts <55 and ≥75 presented with advanced stage at diagnosis and progressed to bone metastasis earlier. Pts ≥75 had decreased performance status, more comorbidities, higher PSA at diagnosis, shorter duration of hormone sensitive disease, and were less likely to receive chemotherapy than pts <75. The percentage of rapid PSA doubling times was highest in the <55 cohort. In multivariate analysis with age as a categorical variate, ECOG 3–4 (HR 2.65), time from diagnosis to both HRPC (HR 0.78) and bone metastasis (HR 0.80), and duration of response to androgen ablation (HR 0.86) remained highly predictive. Conclusions: Age at diagnosis influences OS in HRPC with a bimodal survival curve. Pts <55 and ≥75 present with more aggressive disease, translating into reduced median and 5 yr survivals. Other covariates, especially ECOG status, likely account for the decreased OS in the ≥75 cohort. Conversely, pts <55 had an adjusted HR of 1.60 (p = 0.06). Our study supports a growing body evidence that suggests a poor prognosis in younger men; correlating these differences at the molecular level could lead to better targeted therapies. No significant financial relationships to disclose.

scholarly journals Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Huan-he Ni ◽  
Lin Zhang ◽  
He Huang ◽  
Shu-qin Dai ◽  
Jiang Li
Keyword(s):  
Cervical Cancer ◽  
Proportional Hazards ◽  
Cox Model ◽  
Disease Free Survival ◽  
Suppressor Cells ◽  
Cox Proportional Hazards ◽  
Tumour Cells ◽  
Rank Test ◽  
Independent Factor

Abstract Background Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC). Methods Specimens of paraffin embedded tumour from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson’s or Spearman’s chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan–Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls. Results We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR− MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II–IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P = 0.010) and OS (HR = 5.140, P = 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037). Conclusion Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

MicoRNA-425-5p is a potential prognostic biomarker for cervical cancer

2016 ◽  
Vol 54 (1) ◽  
pp. 127-133 ◽  
Author(s):  
Liwei Sun ◽  
Rong Jiang ◽  
Jinduo Li ◽  
Bin Wang ◽  
Chunhua Ma ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Prognostic Biomarker ◽  
Positive Lymph Node ◽  
Cox Proportional Hazards ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Cervical Disease ◽  
Cancer Tissues

Background MicroRNAs have been implicated in many biological pathways involved in tumourigenesis and can serve as prognostic biomarkers in many cancer types. The present study aims at evaluating the prognostic significance of miR-425-5p in cervical cancer. Methods Real-time polymerase chain reaction was performed to assess the expression levels of miR-425-5p in 35 pairs of cervical cancer tissues and their matched normal tissues as well as serum samples from 40 cervical cancer patients, 13 benign cervical disease patients and 32 healthy controls. The association between miR-425-5p expression levels in tissue and serum, and clinicopathological factors was examined. The correlation between serum miR-425-5p expression levels and overall survival of cervical cancer patients was assessed by Kaplan–Meier analysis and Cox proportional hazards model. Results MiR-425-5p expression levels were significantly increased in cervical cancer tissues compared with matched non-cancerous tissues. Higher expression of miR-425-5p was positively associated with high tumour stage ( P = 0.0003) and positive lymph node metastasis ( P = 0.0107). Serum concentrations of miR-425-5p in cervical cancer patients were significantly higher compared with benign cervical disease and healthy controls. Moreover, the up-regulation of serum miR-425-5p occurred more frequently in cervical cancer patients with high TNM stage ( P = 0.0003) and positive lymph node metastasis ( P = 0.0037). Kaplan–Meier analysis showed that high serum miR-425-5p expression levels predicted poor survival ( P = 0.0571). Cox proportional hazards risk analysis demonstrated that miR-425-5p was an independent prognostic factor for cervical cancer. Conclusion Our study suggests that miR-425-5p is up-regulated in cervical cancer and serum miR-425-5p may serve as a potential prognostic biomarker for cervical cancer.

Prognostic Significance of Pretreatment Thrombocytosis in Cervical Cancer Patients Treated With Definitive Radiotherapy

2015 ◽  
Vol 25 (9) ◽  
pp. 1656-1662 ◽  
Author(s):  
Mahiru Kawano ◽  
Seiji Mabuchi ◽  
Yuri Matsumoto ◽  
Tomoyuki Sasano ◽  
Ryoko Takahashi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Platelet Count ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Initial Diagnosis ◽  
Advanced Clinical Stage ◽  
Definitive Radiotherapy

ObjectiveThe aim of this study was to investigate the prevalence and prognostic significance of an elevated platelet count at the time of the initial diagnosis in patients with cervical cancer who are treated with definitive radiotherapy.MethodsThe baseline characteristics and outcome data of cervical cancer patients who were treated with definitive radiotherapy between November 1993 and December 2011 were collected and retrospectively reviewed. The patients were separated into 2 groups according to their platelet counts. The clinicopathological characteristics and overall survival rates of the 2 groups were compared. A Cox proportional hazards regression model was used to investigate the prognostic significance of an elevated platelet count.ResultsAn elevated platelet count was found to be associated with younger age (P = 0.0003), an advanced clinical stage (P < 0.0001), larger tumors (P = 0.0025), lower hemoglobin levels (P < 0.0001), and more frequent treatment failure (P = 0.0015). Multivariate analysis demonstrated that an advanced clinical stage (hazards ratio [HR], 2.93; 95% confidence interval [CI], 1.47–6.70; P = 0.0015), nonsquamous cell carcinoma histology (HR, 2.67; 95% CI, 1.52–4.42; P = 0.0011), larger tumors (HR, 3.86; 95% CI, 2.18–7.03; P < 0.0001), lower hemoglobin levels (HR, 1.99; 95% CI, 1.34–2.93; P = 0.0008), and an elevated platelet count (HR, 1.65; 95% CI, 1.03–2.56; P = 0.0395) were significant predictors of survival.ConclusionsAn elevated platelet count at the time of the initial diagnosis is an independent prognostic factor in cervical cancer patients who are treated with definitive radiotherapy.

Comorbidities and survival in breast cancer: A retrospective cohort study from an academic institution in southern Illinois.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13624-e13624
Author(s):  
Ruby Maini ◽  
Manjari Rani Regmi ◽  
Priyanka Parajuli ◽  
Odalys Estefania Lara Garcia ◽  
Asad Cheema ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Retrospective Cohort ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Treatment Modalities ◽  
Rank Test ◽  
Electronic Patient Records ◽  
Breast Cancer Patients ◽  
Risk Of Mortality

e13624 Background: Breast cancer is the most common malignancy in females. Early detection and advances in treatment modalities have resulted in decreasing rates of breast cancer related death. While breast cancer survival has improved, risks of death from cardiovascular comorbidities have increased. Our study aims to evaluate survival among breast cancer patients with cardiac comorbidities. Methods: This study was conducted using a retrospective cohort design with use of de-identified hospital electronic patient records. ICD diagnoses codes were used to identify breast cancer patients. Our initial search criteria revealed 1618 patients. Our eligibility criteria included adult patients 18 years and older with newly diagnosed breast cancer from January 1st, 2014 – January 31st, 2017 which yielded 478 patients. All data was collected through retrospective chart review. Analysis was performed with SAS v9.4 software. Qualitative variables were analyzed using Chi-Square Test. Survival curves are estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival are assessed with Cox proportional hazards regression analyses. All significance was assumed at the p < 0.05 level and reported as hazard ratios (HR). Results: Of our 478 patients, the following comorbidities were noted: diabetes n = 98 (21.17%), myocardial infarction (MI) n = 14 (2.98%), heart failure (HF) n = 36 (8.38%), coronary artery disease (CAD) n = 26 (5.75%), hypertension (HTN) n = 261 (55.77%), peripheral vascular disease (PVD) n = 9 (1.95%), hyperlipidemia (HLD) n = 230 (49.15%). Survival analysis was completed on patients with CAD (p = 0.49), HLD (p = 0.40), HTN (p = 0.15), MI (p = 0.52), and HF HR = 6.35 (95% CI 2.40-16.7, p = 0.0002). Pre-existing HF had a higher risk of mortality, which was statistically significant; however, all other single comorbidities were not. Overall survival (OS) in patients with more than one comorbidity HR = 1.36 (1.08-1.69, p = 0.006), was statistically significant. Conclusions: Patients with only one comorbidity be it MI, CAD, HTN, HLD did not have statistically significant results in OS. However, breast cancer patients with pre-existing HF are at 6.35-fold higher risk of mortality than those without HF. Patients with more than one comorbidity listed above were at 1.36-fold higher risk of mortality. Our results indicate that risk factor reduction may help improve survival in patients with breast cancer. Prospective validation of these findings is warranted.

scholarly journals Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

2020 ◽  
Author(s):  
Huan-he Ni ◽  
Lin Zhang ◽  
He Huang ◽  
Shu-qin Dai ◽  
Jiang Li
Keyword(s):  
Cervical Cancer ◽  
Proportional Hazards ◽  
Cox Model ◽  
Disease Free Survival ◽  
Suppressor Cells ◽  
Cox Proportional Hazards ◽  
Tumour Cells ◽  
Rank Test ◽  
Independent Factor

Abstract Background: Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).Methods: Paraffin tumour specimens from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson's or Spearman's chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls.Results: We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR- MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II-IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P= 0.010) and OS (HR = 5.140, P= 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).Conclusion: Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

scholarly journals Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

2020 ◽  
Author(s):  
Huanhe Ni ◽  
Lin Zhang ◽  
Hong-xia Chen ◽  
Shu-qin Dai ◽  
Jiang Li
Keyword(s):  
Cervical Cancer ◽  
Proportional Hazards ◽  
Cox Model ◽  
Disease Free Survival ◽  
Suppressor Cells ◽  
Cox Proportional Hazards ◽  
Tumour Cells ◽  
Rank Test ◽  
Independent Factor ◽  
Chi Square

Abstract Background: Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).Methods: Paraffin tumour specimens from 197 CC patients were collected. The expression of METTL3 and CD33 was measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson's and Spearman's chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan–Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses.Results: We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stages. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. The Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II-IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P= 0.010) and OS (HR = 5.140, P= 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).Conclusion: Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

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