Prognostic Value of PD-L1 and Siglec-15 Expression in Patients with Nasopharyngeal Carcinoma

2021 ◽  
Author(s):  
Ju Zhao ◽  
Hanshan Yang ◽  
Hui Hu ◽  
Chao Liu ◽  
Min Wei ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Immune Escape ◽  
Immunofluorescent Staining ◽  
Rank Test ◽  
Tumor Immune Escape ◽  
Tissue Samples ◽  
Free Survival ◽  
Distant Failure ◽  
Cox Analysis

Abstract Purpose: Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) might be involved in the activation of important pathways related to tumor immune escape, along with programmed death-ligand 1 (PD-L1). We aimed to investigate the correlation between the expression of Siglec-15 and PD-L1 in NPC patients.Patients and methods: We determined the expression of PD-L1 via immunohistochemical staining and that of Siglec-15 via immunofluorescent staining in 182 NPC tissue samples.Results: A significant correlation was identified between the PD-L1 and Siglec-15 expression (P=0.000). Moreover, Kaplan–Meier survival curves showed that PD-L1 expression were associated with improved overall survival (P=0.025) and Siglec-15 expression were associated with improved distant failure-free survival (P=0.048). Meanwhile, multivariate Cox analysis showed that PD-L1 and Siglec-15 were independent predictors of overall survival (P=0.020) and distant failure-free survival (P=0.047), respectively. The results of the log-rank test and Cox regression analyses showed that patients exhibiting no PD-L1/Siglec-15 expression were found to have significant advantages with regard to overall survival, compared to other groups (P=0.037).Conclusion: PD-L1 and Siglec-15 may represent novel biomarkers for predicting NPC patient prognosis. Siglec-15 could be considered as a potential target for the development of therapeutics for NPC treatment in the future.

scholarly journals PGM5 is a promising biomarker and may predict the prognosis of colorectal cancer patients

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yifan Sun ◽  
Haihua Long ◽  
Lin Sun ◽  
Xiujuan Sun ◽  
Liping Pang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Migration And Invasion ◽  
Rank Test ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Invasion And Migration ◽  
Kaplan Meier ◽  
And Migration

Abstract Background Phosphoglucomutase (PGM), a key enzyme in the metabolism of glucose-1-phosphate and glucose-6-phosphate, has been found to be associated with proliferation, invasion, and metastasis of cancer. However, the expression and function of PGM5 in colorectal cancer (CRC) remains unknown. Methods We tested PGM5 mRNA and protein expression levels in 79 CRC tissue and their matched adjacent tissue samples by qRT-PCR and immunohistochemistry, respectively. Overall survival (OS) was estimated with the Kaplan–Meier method and compared between groups with the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk. The cell proliferation, migration and invasion abilities of CRC cells were detected by using CCK-8, Transwell migration and invasion assays, respectively. Results The PGM5 protein levels expression in CRC tissues were significantly lower than those in the adjacent tissues (t = 5.035, P < 0.001), and Kaplan–Meier analysis indicated that low PGM5 expression were significantly associated with poor overall survival (P = 0.0069). Univariate and multivariate analyses demonstrated that PGM5 was an independent risk factor for overall survival (hazard ratio = 0.3951, P = 0.014). PGM5 overexpression significantly inhibited the proliferation, invasion and migration abilities of CRC cells. On the contrary, knockdown of PGM5 promotes the invasion and migration of CRC cells. Conclusions PMG5 regulates proliferation, invasion, and migration in the CRC and decreased PGM5 is associated with poor prognosis. Therefore, PGM5 is a promising biomarker in CRC and decreased PGM5 may predict poor overall survival in patients with CRC.

Deficient necroptosis pathway as a negative prognostic factor in acute myeloid leukemia.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11611-11611
Author(s):  
Silvia Lo Monaco ◽  
Giovanni Marconi ◽  
Maria Chiara Fontana ◽  
Cristina Papayannidis ◽  
Eugenio Fonzi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Rank Test ◽  
Control Group ◽  
Fisher Exact Test ◽  
Copy Number Loss ◽  
Tumor Immune Escape ◽  
Exact Test

11611 Background: Necroptosis is a type of necrotic cell death involving several genes transcription and activation of molecular mechanisms as death receptors, interferon, toll-like receptors, intracellular RNA and DNA sensors.The process is leading by the family of receptor-interacting protein kinase ( RIPK3, RIPK2, RIPK1) and the MLKL substrate. Losses of RIPK3 or MLKL, as well as deficiency in apoptosis, could allow tumor cells to escape the immunomediated cells death (ICD). Methods: We performed SNP Arrays (Cytoscan HD and SNP 6.0, Affymetrix) on a cohort of 300 non-M3 AML patients at diagnosis and we analyzed the Overall Survival (OS) of our patients with deficiency on necroptosis pathways. Survival was analyzed with Kaplan-Mayer method and Log-Rank test. We further analyze the relevance of different prognostic factors by the use of COX-Hazard Ratio statistical analysis. Results: We find that 18 patients presented a loss of RIPK1 or MLKL (nobody presented losses in RIPK3/RIPK2) and 13/18 patients were older than 65 years old. The Overall Survival (OS) of patients with alterations in these genes is significantly lower than control group, with a median OS of 3 vs 6 month respectively (p<.0.001). With Fisher Exact Test we further demonstrate that copy number loss of RIPK1 or MLKL are associate to loss of TP53 or FANCAgenes, complex karyotype and advanced age. COXHR model with RIPK1 or MLKL loss, BRACA1 loss, TP53 mutation, FANCA loss, secondary disease and diagnosis karyotype considered as categorical variable shows that necroptosis deficiency (HR 1.98, CI 95% 1.04-3.78), TP53mutation , and secondary AML are independent negative prognostic factors in an optimal model. Conclusions: Our study shows that losses in necroptosis pathways are an uncommon alteration in AML, prevalent in old population. Moreover, we hypothesize that the loss of genes involved in necroptosis could be a real mechanism of tumor immune-escape and could be a rational to select patients that have high probability to be resistant at chemotherapy promoting ICD mechanism. Acknowledgment: ELN,AIL,AIRC, progetto Regione-Università 2010-12, FP7 NGS-PTL project,HARMONY.

Plasma IL-8 and PD-L1 and overall survival in metastatic castration-resistant prostate cancer patients (mCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17565-e17565
Author(s):  
Hyma Vani Polimera ◽  
Mark Pomerantz ◽  
Kim Leitzel ◽  
Subrina Farah ◽  
Wanling Xie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Immune Escape ◽  
Univariate Analysis ◽  
High Plasma ◽  
Continuous Variable ◽  
High Serum ◽  
Castration Resistant Prostate Cancer ◽  
Blood Draw ◽  
Tumor Immune Escape

e17565 Background: We previously reported the significant prognostic and predictive utility of pretreatment serum PD-L1 in the CCTG MA.31 breast cancer serum bank (SABCS 2018, abstr PD3-10). IL-8 (CXCL8) is a pro-inflammatory cytokine that binds to CXCR1 and CXCR2 and promotes tumor immune escape and progression. High serum IL-8 levels are associated with poor prognosis in many cancers, and have recently been reported to predict for reduced overall survival (OS) to nivolumab in lung cancer and melanoma (ASCO 2018, abstr #3025). Here we correlated plasma IL-8 and PD-L1 levels with OS in mCRPC patients. Methods: 201 metastatic CRPC patients had EDTA plasma available for this retrospective analysis. Patient eligibility included chemotherapy-naive mCRPC patients. The ELLA immunoassay platform (ProteinSimple, San Jose, CA) was utilized to quantitate plasma IL-8 and PD-L1. Cox regression assessed hazard ratio (HR) for OS using both categorical (median) and continuous (log-transformed) biomarkers. Results: In univariate analysis, higher plasma IL-8 levels were significantly associated with reduced OS when analyzed as a continuous variable (HR = 1.53; p = 0.003) and were of borderline significance at the median cutpoint (HR = 1.32; p = 0.069; 20.9 vs 31.5 mos median OS). Plasma PD-L1 levels were not significantly associated with OS when analyzed as a continuous variable (p = 0.17), but increased levels were significant when analyzed at the median cutpoint (HR = 1.36; p = 0.044; 21.9 vs 29.0 mos median OS). When plasma IL-8 and PD-L1 levels were combined (median cutpoints), plasma IL-8 high / PD-L1 high patients (n = 58) had a significantly shorter OS vs the plasma IL-8 low / PD-L1 low patients (n = 58) (HR = 1.69; p = 0.009; 19.3 vs 32.9 mos median OS, respectively). In multivariate analysis, when adjusted for biopsy Gleason score, age, PSA, and ECOG PS (all at time of blood draw), only high plasma IL-8 (on a continuous basis) was significantly associated with reduced OS (HR = 1.43; p = 0.019). Conclusions: In mCRPC patients, high plasma IL-8 and PD-L1 levels were associated with reduced OS (separately and combined). Circulating IL-8 and PD-L1 evaluation may inform prognosis in mCRPC and could be considered as biomarkers in future studies determining response to immune checkpoint inhibitor and anti-IL8 therapy.

scholarly journals EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1410
Author(s):  
Anna Buchholz ◽  
Aurelia Vattai ◽  
Sophie Fürst ◽  
Theresa Vilsmaier ◽  
Christina Kuhn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Vulvar Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Common Finding ◽  
Cancer Tissue ◽  
Vulvar Carcinoma ◽  
Tissue Samples

New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

2021 ◽  
pp. 1-9
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

Hyaluronan heterogeneity in pancreatic ductal adenocarcinoma, primary tumors, and sites of metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16231-e16231
Author(s):  
Veronica Placencio-Hickok ◽  
Marie Lauzon ◽  
Natalie Moshayedi ◽  
Michelle Guan ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastasis ◽  
Regression Model ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
High Status ◽  
Free Survival ◽  
Pdac Tissue ◽  
Treatment Naïve

e16231 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with an estimated five-year survival rate of 10%. The dense desmoplastic stroma in PDAC contributes to its aggressive nature and treatment resistance. Among the components comprising the stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci in PDAC. However, the effects of treatment and location of HA expression as well as the role of CD44, a known receptor for HA, on HA as a biomarker signature remain unknown. Thus, we investigated the potential of HA as a biomarker in primary PDAC and metastases. Methods: PDAC tissue from primary (n = 43) and metastatic (n = 66) sites were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained with H&E, HA using a histochemical assay, and CD44 by immunohistochemistry. HA staining was scored according to the proportion of stromal staining at an intensity greater than the background stroma. HA status was defined as ≥ 50% staining being HA high and < 50% as being HA low. CD44 staining was recorded as an H-score (percentage of tumor cells staining multiplied by intensity of staining on a scale from 0 to 3). Associations between HA levels and the requested variables were examined with t-test, Wilcoxon rank-sum test, Chi-squared test, Fisher’s exact test, or Cox regression model where appropriate. Kaplan-Meier curves were created to assess progression free survival and overall survival. Analyses were performed using SAS 9.4 with two-sided tests and a significance level of 0.05. Results: HA score was significantly higher in primary PDAC tissue compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastasis compared to other sites of metastasis (p = 0.0478). In the liver metastasis tissue, HA score trended lower in patients with previously treated tissue compared to treatment naïve tissue (p = 0.0622). In the treatment naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively). Using HA score and CD44 in a Cox regression model demonstrated that for every one unit increase in HA score, the risk for recurrence/progression increased by 4.4% at any fixed point in time, adjusting for CD44 score (p = 0.0049). Conclusions: HA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.

scholarly journals Combined Effect of IL-12Rβ2 and IL-23R Expression on Prognosis of Patients with Laryngeal Cancer

2018 ◽  
Vol 50 (3) ◽  
pp. 1041-1054 ◽  
Author(s):  
Ye Tao ◽  
Tianchang Tao ◽  
Neil Gross ◽  
Xuyun Peng ◽  
Ying Li ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Laryngeal Cancer ◽  
Cox Regression ◽  
Tumor Infiltrating Lymphocytes ◽  
Combined Effect ◽  
Interleukin 12 ◽  
Rank Test ◽  
Tissue Samples ◽  
Functional Studies

Background/Aims: This study aimed to pathologically elucidate the roles of interleukin-12 receptor (IL-12R) β2 and interleukin-23 receptor (IL-23R) expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment and to determine their combined effect on prognosis of laryngeal cancer (LC). Methods: The tumor-cell expression scores and TIL positivity ratiosof IL-12Rβ2 and IL-23R in matched LC and normal laryngeal tissue samples from 61 LC patients were measured via immunohistochemistry (IHC). We adopted a linear regression model to analyze the correlation between IL-12Rβ2 and IL-23R expression in tumor cells and TIL ratios. TheKaplan-Meier log-rank test and Cox regression hazard ratios were used to analyze survival. Results: LC tumor cells had a higher IL-12Rβ2 expression and TIL ratio than IL-23R expression and TIL ratio. The significant correlations between IL-12Rβ2 and IL-23R expression and TIL ratios were identified in LC tissues, particularly in well-differentiated LC. Furthermore, either high tumor cell IL-12Rβ2 or low IL-23R expression had better survival than its corresponding low or high expression, respectively. Similar results did for IL-12Rβ2 ratio and IL-23R ratio. Finally, patients with both high IL-12Rβ2 and low IL-23R had the best prognosis among any other combined groups with both gene expression (HR, 0.1; 95% CI, 0.0-0.8). Likewise, patients with positive ratios of high IL-12Rβ2 and low IL-23R TILs had the best survival (HR, 0.1; 95% CI, 0.0-0.4). Conclusion: IL-12Rβ2 and IL-23R create a homeostasis within the tumor cells and TILs, and this homeostasis affects prognosis. While the intrinsic mechanisms of epigenetic immunoediting for IL-12Rβ2 and IL-23R remain unknown, additional larger and functional studies are warranted for validation.

Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus

2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Maxillary Sinus ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Cox Regression ◽  
Rank Test ◽  
Controlled Clinical Trial ◽  
Log Rank Test ◽  
Kaplan Meier

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.

scholarly journals Development and Validation of a Unique Gignature of Cancer Stemness-related Genes for Predicting the Overall survival of Colorectal Cancer Patients

2020 ◽  
Author(s):  
Ran Wei ◽  
Jichuan Quan ◽  
Shuofeng Li ◽  
Zhao Lu ◽  
Xu Guan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Cancer Stemness ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB) and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high mRNAsi scores are associated with poor overall survival in stage Ⅳ CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 2 key modules and 34 key genes as prognosis-related candidate biomarkers. Finally, a 3-gene prognostic signature (PARPBP, KNSTRN and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusions: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

scholarly journals Expression profiling analysis of autophagy-related genes in cervical cancer

2021 ◽  
Author(s):  
Zhiyuan Huang ◽  
He Wang ◽  
Min Liu ◽  
Xinrui Li ◽  
Lei Zhu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cervical Cancer ◽  
Overall Survival ◽  
Risk Score ◽  
Roc Curve ◽  
Normal Tissue ◽  
Cox Regression ◽  
Risk Group ◽  
Differentially Expressed ◽  
Tissue Samples

Abstract Background: It has been demonstrated by studies globally that autophagy took part in the development of cervical cancer (CC). Few studies concentrated on the correlation between overall survival and CC patients. We retrieved significant autophagy-related genes (ARGs) correlated to the process of cervical cancer. They may be used as prognosis marker or treatment target for clinical application.Methods: Expressions level of genes in cervical cancer and normal tissue samples were obtained from GTEx and TCGA database. Autophagy-related genes (ARGs) were retrieved accroding to the gene list from HaDB. Differentially expressed autophagy related genes (DE-ARGs) related to cervical cancer were identified by Wilcoxon signed-rank test. ClusterProfiler package worked in R software was used to perform GO and KEGG enrichment analyses. Univariate propotional hazard cox regression and multivariate propotional hazard cox regressions were applied to identify DE-ARGs equipped with prognostic value and other clinical independent risk factors. ROC curve was drawn for comparing the survival predict feasibility of risk score with other risk factors in CC patients. Nomogram was drawn to exhibit the prediction model constructed accroding to multivariate cox regression. Correlations between Differentially expressed autophagy related genes (DE-ARGs) and other clinical features were investigated by t test or Cruskal wallis analysis. Correlation between Immune and autophagy in cervical cancer was investigated by ssGSEA and TIMER database. Results: Fifty-six differentially expressed ARGs (DE-ARGs) were retrieved from cervical cancer tissue and normal tissue samples. GO enrichment analysis showed that these ARGs involved in autophagy, ubiquitination of protein and apoptosis. Cox regression medel showed that there were six ARGs significantly associated with overall survival of cervical caner patients. VAMP7 (HR = 0.599, P= 0.033) and TP73 (HR = 0.671, P= 0.014) played protective roles in survival among these six genes. Stage (Stage IV vs Stage I HR = 3.985, P<0.001) and risk score (HR = 1.353, P< 0.001) were sorted as independent prognostic risk factors based on multivariate cox regression. ROC curve validated that risk score was preferable to predict survival of CC patients than other risk factors. Additionally, we found some of these six predictor ARGs were correlated significantly in statistic with tumor grade or stage, clinical T stage, clinical N stage, pathology or risk score (all P< 0.05). The immune cells and immune functions showed a lower activity in high risk group than low risk group which is distincted by median risk score. Conclusion: Our discovery showed that autophagy genes involved in the progress of cervical cancer. Many autophagy-related genes could probably serve as prognostic biomarkers and accelerate the discovery of treatment targets for CC patients.

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