Multi-Omics Analysis of the Effects of Smoking on Human Tumors

Comprehensive studies on cancer patients with different smoking histories, including non-smokers, former smokers, and current smokers, remain elusive. Therefore, we conducted a multi-omics analysis to explore the effect of smoking history on cancer patients. Patients with smoking history were screened from The Cancer Genome Atlas database, and their multi-omics data and clinical information were downloaded. A total of 2,317 patients were included in this study, whereby current smokers presented the worst prognosis, followed by former smokers, while non-smokers showed the best prognosis. More importantly, smoking history was an independent prognosis factor. Patients with different smoking histories exhibited different immune content, and former smokers had the highest immune cells and tumor immune microenvironment. Smokers are under a higher incidence of genomic instability that can be reversed following smoking cessation in some changes. We also noted that smoking reduced the sensitivity of patients to chemotherapeutic drugs, whereas smoking cessation can reverse the situation. Competing endogenous RNA network revealed that mir-193b-3p, mir-301b, mir-205-5p, mir-132-3p, mir-212-3p, mir-1271-5p, and mir-137 may contribute significantly in tobacco-mediated tumor formation. We identified 11 methylation driver genes (including EIF5A2, GBP6, HGD, HS6ST1, ITGA5, NR2F2, PLS1, PPP1R18, PTHLH, SLC6A15, and YEATS2), and methylation modifications of some of these genes have not been reported to be associated with tumors. We constructed a 46-gene model that predicted overall survival with good predictive power. We next drew nomograms of each cancer type. Interestingly, calibration diagrams and concordance indexes are verified that the nomograms were highly accurate for the prognosis of patients. Meanwhile, we found that the 46-gene model has good applicability to the overall survival as well as to disease-specific survival and progression-free intervals. The results of this research provide new and valuable insights for the diagnosis, treatment, and follow-up of cancer patients with different smoking histories.

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Development and Validation of a Novel 13-Genes Prognostic Model for Colon Cancer

10.21203/rs.3.rs-378434/v1 ◽

2021 ◽

Author(s):

Duo Yun ◽

Zhirong Yang

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Prognostic Value ◽

Risk Model ◽

Malignant Tumors ◽

Expression Profiles ◽

The Cancer Genome Atlas ◽

Pathway Enrichment

Abstract Colon cancer is one of the most common malignant tumors in the world. The purpose of this study is to explore the prognostic value of genes in colon cancer. After analyzing gene expression profiles, differential expressed genes between 39 normal tissues and 398 tumor tissues were identified from The Cancer Genome Atlas database. We use Cox and lasso regression to find genes related to prognosis. Through analysis, 13 genes were found to predict the overall survival of colon cancer patients. In addition, the external comparing of gene expression and the single prognostic gene survival analysis were made. Finally, pathway enrichment and mutation status of each gene were also analyzed. After a series of bioinformatics analysis, we select 13 survival-related signature and established a prognostic risk model based on these genes. The prognostic risk model was developed to comprehensively predict the overall survival of colon cancer patients. The prognostic value of the 13-genes (CLDN23,HAND1,IL23A,KLHL35,SIX2,UPK2,HOXC11,KRT6B,SRCIN1,TNNI3,TYRO3,MIR6835,LINC02474) related risk score for each colon cancer patent was calculated to predict the survival. Furthermore, five genes (SIX2 MIR6835 LINC02474 CLDN23 HOXC11) were significantly associated with overall survival (OS). The KEGG pathway enrichment results suggested that most of the pathways are related to the occurrence, metabolism, proliferation and invasion of the tumor cells. It was found that the expression of 13-genes signature can be used as prognostic indicator for colon cancer patients. The 13-genes signature predictive model may help clinicians provide a prognosis and personalized treatment for colon cancer patients.

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Downregulation of B3GNT6 Predicts Poor Outcome in Colorectal Cancer Patients

10.21203/rs.3.rs-127044/v1 ◽

2020 ◽

Author(s):

Chen Yang ◽

Changhao Huang ◽

Pengwei Zeng ◽

Heyuan Huang ◽

Zhikang Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Prognostic Marker ◽

Protein Level ◽

Mrna Level ◽

The Cancer Genome Atlas ◽

Cancer Tissue ◽

Poor Overall Survival ◽

Colorectal Cancer Patients

Abstract Background: B3GNT6 encodes the core 3 synthase in O-glycan biosynthesis. It is commonly expressed in the GI tract, while its clinical significance in colorectal cancer remains largely unknown.Methods: We gathered mRNA transcriptomic sequencing data from 3 Gene Expression Omnibus (GEO) datasets (GSE37182, GSE39582, GSE103512) and The Cancer Genome Atlas (TCGA) to compare the B3GNT6 mRNA level between colorectal cancer tissues and normal tissues and to evaluate its value as a prognostic marker. We further validated this in protein level using online database Human Protein Atlas and with immunohistochemical staining of B3GNT6 with our own cohort. Results: B3GNT6 expression was downregulated in colorectal cancer tissue compared with that in normal tissue in both mRNA and in protein level. Downregulation of B3GNT6 was associated with poor overall survival of colorectal cancer in GSE39582 and in TCGA database. Low B3GNT6 mRNA level was significantly associated with chromosome stable (CIN negative) and KRAS mutated group colorectal cancer patient. GSEA revealed that low B3GNT6 level in colorectal cancer is associated with upregulated proteasome activity.Conclusions: Downregulated B3GNT6 was correlated with poor overall survival of colorectal cancer patients. B3GNT6 could be used as a good prognostic marker in colorectal cancer.

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Development of a novel prognostic signature for predicting the overall survival of bladder cancer patients

Bioscience Reports ◽

10.1042/bsr20194432 ◽

2020 ◽

Vol 40 (6) ◽

Author(s):

Huamei Tang ◽

Lijuan Kan ◽

Tong Ou ◽

Dayang Chen ◽

Xiaowen Dou ◽

...

Keyword(s):

Dna Methylation ◽

Overall Survival ◽

Bladder Cancer ◽

Cancer Patients ◽

Cox Regression ◽

Test Group ◽

Training Group ◽

The Cancer Genome Atlas ◽

Methylation Site ◽

Cox Regression Analysis

Abstract Background: Bladder cancer is one of the most common malignancies. So far, no effective biomarker for bladder cancer prognosis has been identified. Aberrant DNA methylation is frequently observed in the bladder cancer and holds considerable promise as a biomarker for predicting the overall survival (OS) of patients. Materials and methods: We downloaded the DNA methylation and transcriptome data for bladder cancer from The Cancer Genome Atlas (TCGA), a public database, screened hypo-methylated and up-regulated genes, similarly, hyper-methylation with low expression genes, then retrieved the relevant methylation sites. Cox regression analysis was used to identify a nine-methylation site signature of a training group. Predictive ability was validated in a test group by receiver operating characteristic (ROC) analysis. Results: We identified nine bladder cancer-specific methylation sites as potential prognostic biomarkers and established a risk score system based on the methylation site signature to evaluate the OS. The performance of the signature was accurate, with area under curve was 0.73 in the training group and 0.71 in the test group. Taking clinical features into consideration, we constructed a nomogram consisting of the nine-methylation site signature and patients’ clinical variables, and found that the signature was an independent risk factor. Conclusions: Overall, the significant nine methylation sites could be novel prediction biomarkers, which could aid in treatment and also predict the overall survival likelihoods of bladder cancer patients.

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Overall survival and complications of cancer therapy in HIV-positive cancer patients on HAART compared to HIV-negative cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.30_suppl.276 ◽

2014 ◽

Vol 32 (30_suppl) ◽

pp. 276-276

Author(s):

Kelly Ann Fritz ◽

David D. Stenehjem ◽

Stephanie A. Sanders ◽

Adam Louis Cohen

Keyword(s):

Overall Survival ◽

Cancer Therapy ◽

Febrile Neutropenia ◽

Cancer Patients ◽

Patient Population ◽

Hiv Positive ◽

Cancer Type ◽

Infection Prophylaxis ◽

Hiv Negative

276 Background: HIV-positive patients are living longer and are at higher risk for any type of cancer, not only traditional AIDS-defining cancers (ADC). This study aims to assess our overall survival rate in HIV-positive cancer patients compared to HIV-negative patients, and identify differences in complications of cancer therapy in order to ensure quality of care and outcomes in this patient population. Methods: HIV-positive patients ≥ 18 years of age with a diagnosis of cancer in the Huntsman Cancer Institute Tumor Registry from 2008-2013 were matched to HIV-negative cancer patients by cancer type, stage, age, and sex. Overall survival (OS), admission for febrile neutropenia (FN), total hospital length (LOS) of stay for any reason, and the total number of blood transfusions were assessed. Kaplan-Meier methodology was used to assess differences in cancer survival. Results: A total of 55 HIV-positive patients and 40 HIV-negative patients were included. HIV-positive patients were younger at cancer diagnosis than HIV-negative patients, 50 vs. 56 years old (p = 0.0017). A trend for reduced median OS in HIV-positive patients was observed compared to HIV-negative patients (HR 1.81; 95% CI 0.77-4.71; p = 0.1835). One-year OS was 78% for HIV-positive vs 88% for HIV-negative patients (p = 0.2673). Numerically an increased mean number of hospital admissions for FN (0.7 ± 2.0 vs. 0.4 ± 1.3; p = 0.2663), transfusions (2.5 ± 12.7 vs. 0.9 ± 2.5; p = 0.4907), and inpatient LOS (12.7 ± 23.6 vs. 7.0 ± 13.0; p = 0.2381) were observed in the HIV-positive group compared to the HIV-negative group, however this did not meet statistical significance. Conclusions: This retrospective study highlights a trend for a reduction in survival and increased FN admissions, LOS and transfusion requirements in HIV-positive patients with cancer. We have identified a need for improvement in supportive care treatments such as primary febrile neutropenia prophylaxis, opportunistic infection prophylaxis, and anemia management to improve the quality of cancer treatment in this patient population.

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Clinical profile, pathological characteristics, mutational profile and disease outcome of non-small cell lung cancer patients treated at the Benavides Cancer Institute-University of Santo Tomas Hospital : A five-year study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20580 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20580-e20580

Author(s):

Maria Diana Aileen Chua Bautista ◽

Priscilla B. Caguioa

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Survival Rates ◽

Small Cell ◽

Smoking History ◽

Small Cell Lung ◽

Lung Cancer Patients

e20580 Background: Lung cancer is the most commonly diagnosed cancer worldwide and its incidence continues to grow. Lung cancer mortality and survival rates vary markedly by race and ethnicity resulting into a public health burden that differs by population subgroups. This study determined the association of the clinical profile, pathological characteristics and mutational profile with the disease outcome of Non Small Cell Lung Cancer patients at the Benavides Cancer Institute – University of Santo Tomas Hospital from January 1, 2007 to December 31, 2011. Methods: This is a retrospective descriptive study. Medical records of all of patients diagnosed with non-small cell lung cancer were included. Results: A total of 80 patients with non small cell lung cancer were treated, 78.75% (63) were adenocarcinoma and 13.75% (11) were squamous cell carcinoma. Overall 5-year survival rate was at 5%. The 1 year, 2-year, 3-year survival rates were 38.75%, 21.25% and 12.5% respectively with the mean survival time of 1.6 years. The mean survival time of patients who received adjuvant treatment was 26 months, while for metastatic patients was 18 months. Only the stage at time of diagnosis was correlated with overall survival. Age, gender, family history, smoking history, number of pack years smoking history, histologic subtype, response after first line of treatment and sites of metastases were not associated with overall survival. EGFR mutational analysis was not performed in this study since it was not the standard of care and had limited availability in low to middle income countries at the time of the study period. Conclusions: Similar to global incidence, adenocarcinoma remains the most common type of lung cancer in our center. Stage at diagnosis predicts overall survival among lung cancer patients. There is a need for molecular immunotyping to further characterize patients and response to treatment.

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The impact of routine ESAS use on overall survival: Results of a population-based retrospective matched cohort analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6509 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6509-6509 ◽

Cited By ~ 6

Author(s):

Lisa Catherine Barbera ◽

Rinku Sutradhar ◽

Craig Earle ◽

Nicole Mittmann ◽

Hsien Seow ◽

...

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Cox Regression ◽

Cohort Analysis ◽

Symptom Assessment ◽

Assessment System ◽

Cancer Type ◽

Matched Cohort ◽

Study Objective ◽

The Impact

6509 Background: The study objective was to examine the impact of routine Edmonton Symptom Assessment System (ESAS) use on overall survival among adult cancer patients. We hypothesized that patients exposed to ESAS would have better overall survival rates than those who didn’t have ESAS. Methods: The effect of ESAS screening on survival was evaluated in a retrospective matched cohort study. The cohort included all Ontario patients aged 18 or older who were diagnosed with cancer between 2007 and 2015. Patients completing at least one ESAS assessment during the study were considered exposed. The index date was the day of their first ESAS assessment. Follow up time for each patient was segmented into one of three phases: initial, continuing, or palliative care. Exposed and unexposed patients were matched 1:1 using hard (birth year ± 2 years, cancer diagnosis date ± 1 year, cancer type and sex) and propensity-score matching (14 measures including cancer stage, treatments received, and comorbidity). Matched patients were followed until death or the end of study at Dec 31, 2015. Kaplan-Meier curves and multivariable Cox regression were used to evaluate the impact of ESAS on survival. Results: There were 128,893 pairs well matched on all baseline characteristics (standardized difference < 0.1). The probability of survival within the first 5 years was higher among those exposed to ESAS compared to those who were not (73.8% vs. 72.0%, P-value < 0.0001). In the multivariable Cox regression model, ESAS assessment was significantly associated with a decreased mortality risk (HR: 0.49, 95% CI: 0.48-0.49) and this protective effect was seen across all phases. Conclusions: ESAS exposure is associated with improved survival in cancer patients, in all phases of care. To the extent possible, extensive matching methods have mitigated biases inherent to observational data. This provides real world evidence of the impact of routine symptom assessment in cancer care.

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Advising Parents to Stop Smoking: Pediatricians' and Parents' Attitudes

PEDIATRICS ◽

10.1542/peds.91.2.296 ◽

1993 ◽

Vol 91 (2) ◽

pp. 296-300 ◽

Cited By ~ 7

Author(s):

Barbara L. Frankowski ◽

Sheila O. Weaver ◽

Roger H. Secker-Walker

Keyword(s):

Smoking Cessation ◽

Adverse Effects ◽

Response Rate ◽

Smoking History ◽

Parental Age ◽

Smoking Cessation Advice ◽

Quit Smoking ◽

Stop Smoking ◽

Passive Smoke ◽

Former Smokers

Pediatricians are in a unique position to address the issues of smoking cessation with parents. Vermont pediatricians and parents of their patients were surveyed to assess attitudes about giving and receiving smoking cessation advice. A questionnaire was mailed to all pediatricians in Vermont, and 72 valid responses were received, for a response rate of 91%. Forty percent of pediatricians routinely took a smoking history from parents and 11% recorded this information in the child's chart. Most pediatricians (94%) reported advising at least 60% of smoking parents to quit, and they spent an average of 4.4 minutes doing this. Barriers to giving advice were lack of time (42%), feeling that parents did not expect advice (25%), and feeling ill at ease giving the advice (25%). Only 8.5% of pediatricians had received training in how to give smoking cessation advice, but 87% were willing to learn methods to give advice briefly. Six hundred seventy-six parents from randomly selected pediatric practices were interviewed. The average parental age was 32, and 84% were women; 49% had never smoked, 30% were former smokers, and 21% were current mokers. Current smokers were less likely to agree with statements about the adverse effects of passive smoke on children. Most parents (56%) felt that pediatricians should give quit-smoking advice to parents, and 52% of smoking parents reported that they would welcome advice. Only 30% of current smokers said advice would bother them somewhat, and 15% had more negative reactions. Parents and pediatricians agreed on the best opportunities to give quit-smoking advice. Since 91% of parents said they intended to quit smoking sometime, and since pediatrician-delivered quit-smoking advice would be acceptable to them, it would be worthwhile for pediatricians to learn methods of delivering advice succinctly.

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Smoking, Obesity and Overall Survival in Non-Hodgkin Lymphoma (NHL): A Population-Based Study.

Blood ◽

10.1182/blood.v108.11.4649.4649 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4649-4649

Author(s):

Susan M. Geyer ◽

Lindsay M. Morton ◽

Thomas M. Habermann ◽

Cristine Allmer ◽

Scott Davis ◽

...

Keyword(s):

Overall Survival ◽

Los Angeles ◽

Population Based ◽

Cox Proportional Hazards ◽

Smoking History ◽

Primary Lymphoma ◽

Continuous Measure ◽

Former Smokers ◽

The Impact

Abstract Background: Several studies suggest that smoking and obesity may increase the risk of developing NHL, but the impact of these factors on survival is relatively unexplored. One recent population-based Italian study found that smoking may negatively impact overall survival. Methods: We evaluated the association of body mass index (BMI) and cigarette smoking on overall survival in 1,286 patients who participated in a population-based case-control study conducted through the Surveillance, Epidemiology, and End Results (SEER) cancer registries in Detroit, Iowa, Seattle and Los Angeles. BMI (on 1189 participants) and a smoking history (on 471 participants) were obtained through in-person interviews. Histology, stage, presence of B symptoms, first course of therapy, date of last follow-up, and vital status were derived from linkage to registry databases at each study site in the spring of 2005. Hazard Ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards models, while adjusting for demographic and clinical factors. Results: The median age at diagnosis was 58 years (range: 16 – 74), and the most common histologies were DLBCL (33%), follicular (25%), SLL/CLL (12%), marginal zone (9%), mantle cell (4%) and Peripheral T-cell (3%). The median BMI was 26.6 (range: 16.2 – 47.3), and 26% of patients were classified as obese (i.e. BMI >30). Of patients with a smoking history, 47% had never smoked, 19% were active smokers at diagnosis, and 34% were former smokers. No significant differences were observed between those with and without tobacco use data in terms of primary lymphoma characteristics. Overall survival (OS) was defined as time from diagnosis to death due to any cause. Median follow-up on all living patients was 58 months (range: 4 – 78), and 333 patients had died. When BMI was assessed as a continuous measure, it was borderline significantly associated with OS (p=0.050). An indicator of whether or not BMI > 30 was also significantly associated with OS (HR=1.30; 95% CI: 1.01 – 1.68; p=0.042). Ever vs. never smokers also exhibited a survival disadvantage (HR=1.66; 95% CI: 1.12 – 2.44; p=0.011). When broken down further, former smokers who had smoked for >10 years (HR=1.61; 95% CI: 1.02 – 2.52; p=0.039) and current smokers (HR=1.79; 95% CI: 1.07 – 3.02; p=0.028) were at a survival disadvantage over those who had never smoked. When both smoking and BMI status were included in the model, only the indicator of being a current smoker remained statistically significant (p=0.031), with a trend toward decreased survival for former smokers who had smoked >10 years (p=0.061) and those with BMI >30 (p=0.058). Conclusions: NHL patients who smoke or are obese had a poorer overall survival. These observations warrant further investigation, including whether interventions for smoking cessation or weight loss can impact NHL survival.

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Tobacco smoking and cessation and PD-L1 inhibitors in non-small cell lung cancer (NSCLC): a review of the literature

ESMO Open ◽

10.1136/esmoopen-2018-000406 ◽

2018 ◽

Vol 3 (6) ◽

pp. e000406 ◽

Cited By ~ 22

Author(s):

Jan Norum ◽

Carsten Nieder

Keyword(s):

Lung Cancer ◽

Smoking Cessation ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Tobacco Smoking ◽

Small Cell ◽

Smoking History ◽

Cochrane Library ◽

Small Cell Lung ◽

Former Smokers

BackgroundProgrammed death ligand 1 (PD-L1) targeting immunotherapies, as pembrolizumab and nivolumab, have significantly improved outcome in patients with non-small cell lung cancer (NSCLC). Tobacco smoking is the number one risk factor for lung cancer and is linked to 80%–90% of these cancers. Smoking during cancer therapy may influence on radiotherapy and chemotherapy outcome. We aimed to review the knowledge in immunotherapy.Patients and methodsA systematic review was done. We searched for documents and articles published in English language and registered in Cochrane Library, National Health Service (NHS) Centre for Reviews and Dissemination (CRD), Embase or Medline. The search terms were (A) (Lung cancer or NSCLC) with (pembrolizumab or nivolumab) with PD-L1 with (tobacco or smoking) and (B) Lung Neoplasms and Immunotherapy and (smoking cessation or patient compliance). 68 papers were detected and two more were added during review process (references) and six based on information from the manufacturers.ResultsNine papers were selected. High PD-L1 expression (≥50%) was correlated with current/ever smoking history in three studies. Six studies revealed a higher overall response rate (ORR) among current/former smokers. The ORR was generally (six studies) better among the current/former smoker group. So also when tumours had a molecular ‘smoking signature’ (one study). This was probably due to a higher mutational burden. In two studies, minor or no difference was revealed.One study (KEYNOTE-024) compared former and current smokers, and documented pembrolizumab being more effective among former smokers than current smokers.ConclusionsTobacco smoking patients with NSCLC generally have a higher PD-L1 tumour proportion score and experience a better ORR of immunotherapy than no smokers. There is little evidence on the effect of smoking during immunotherapy, but one study (KEYNOTE-024) may indicate survival gains of smoking cessation.

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Clinical Characteristics of Patients With Lung Adenocarcinomas Harboring BRAF Mutations

Journal of Clinical Oncology ◽

10.1200/jco.2010.33.1280 ◽

2011 ◽

Vol 29 (15) ◽

pp. 2046-2051 ◽

Cited By ~ 408

Author(s):

Paul K. Paik ◽

Maria E. Arcila ◽

Michael Fara ◽

Camelia S. Sima ◽

Vincent A. Miller ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Lung Adenocarcinoma ◽

Clinical Characteristics ◽

Median Overall Survival ◽

Smoking History ◽

Egfr Mutations ◽

Braf Mutations ◽

Former Smokers ◽

Lung Adenocarcinomas

Purpose BRAF mutations occur in non–small-cell lung cancer. Therapies targeting BRAF mutant tumors have recently been identified. We undertook this study to determine the clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. Patients and Methods We reviewed data from consecutive patients with lung adenocarcinoma whose tumors underwent BRAF, EGFR, and KRAS mutation testing as well as fluorescence in situ hybridization for ALK rearrangements. Patient characteristics including age, sex, race, performance status, smoking history, stage, treatment history, and overall survival were collected. Results Among 697 patients with lung adenocarcinoma, BRAF mutations were present in 18 patients (3%; 95% CI, 2% to 4%). The BRAF mutations identified were V600E (50%), G469A (39%), and D594G (11%). Mutations in EGFR were present in 24%, KRAS in 25%, and ALK translocations in 6%. In contrast to patients with EGFR mutations and ALK rearrangements who were mostly never smokers, all patients with BRAF mutations were current or former smokers (P < .001). The median overall survival of advanced-stage patients with BRAF mutations was not reached. In comparison, the median overall survival of patients with EGFR mutations was 37 months (P = .73), with KRAS mutations was 18 months (P = .12), and with ALK rearrangements was not reached (P = .64). Conclusion BRAF mutations occur in 3% of patients with lung adenocarcinoma and occur more commonly in current and former smokers. The incidence of BRAF mutations other than V600E is significantly higher in lung cancer than in melanoma.

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