Bacterial Diversity Correlates with Overall Survival in Cancers of the Head and Neck, Liver, and Stomach

One in five cancers is attributed to infectious agents, and the extent of the impact on the initiation, progression, and disease outcomes may be underestimated. Infection-associated cancers are commonly attributed to viral, and to a lesser extent, parasitic and bacterial etiologies. There is growing evidence that microbial community variation rather than a single agent can influence cancer development, progression, response to therapy, and outcome. We evaluated microbial sequences from a subset of infection-associated cancers—namely, head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA). A total of 470 paired tumor and adjacent normal samples were analyzed. In STAD, concurrent presence of EBV and Selemonas sputigena with a high diversity index were associated with poorer survival (HR: 2.23, 95% CI 1.26–3.94, p = 0.006 and HR: 2.31, 95%CI 1.1–4.9, p = 0.03, respectively). In LIHC, lower microbial diversity was associated with poorer overall survival (HR: 2.57, 95%CI: 1.2, 5.5, p = 0.14). Bacterial within-sample diversity correlates with overall survival in infection-associated cancers in a subset of TCGA cohorts.

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Heme Biosynthesis mRNA Expression Signature: Towards a Novel Prognostic Biomarker in Patients with Diffusely Infiltrating Gliomas

Cancers ◽

10.3390/cancers13040662 ◽

2021 ◽

Vol 13 (4) ◽

pp. 662

Author(s):

Mario Mischkulnig ◽

Barbara Kiesel ◽

Daniela Lötsch ◽

Thomas Roetzer ◽

Martin Borkovec ◽

...

Keyword(s):

Overall Survival ◽

Mrna Expression ◽

Postoperative Management ◽

Heme Biosynthesis ◽

The Cancer Genome Atlas ◽

Sequencing Data ◽

Who Grade ◽

Expression Signature ◽

Cancer Genome Atlas ◽

The Impact

Diffusely infiltrating gliomas are characterized by a variable clinical course, and thus novel prognostic biomarkers are needed. The heme biosynthesis cycle constitutes a fundamental metabolic pathway and might play a crucial role in glioma biology. The aim of this study was thus to investigate the role of the heme biosynthesis mRNA expression signature on prognosis in a large glioma patient cohort. Glioma patients with available sequencing data on heme biosynthesis expression were retrieved from The Cancer Genome Atlas (TCGA). In each patient, the heme biosynthesis mRNA expression signature was calculated and categorized into low, medium, and high expression subgroups. Differences in progression-free and overall survival between these subgroups were investigated including a multivariate analysis correcting for WHO grade, tumor subtype, and patient age and sex. In a total of 693 patients, progression-free and overall survival showed a strictly monotonical decrease with increasing mRNA expression signature subgroups. In detail, median overall survival was 134.2 months in the low, 79.9 months in the intermediate, and 16.5 months in the high mRNA expression signature subgroups, respectively. The impact of mRNA expression signature on progression-free and overall survival was independent of the other analyzed prognostic factors. Our data indicate that the heme biosynthesis mRNA expression signature might serve as an additional novel prognostic marker in patients with diffusely infiltrating gliomas to optimize postoperative management.

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MEX3A and MEX3B as Potential Prognostic Indicators in Stomach Adenocarcinoma

10.21203/rs.3.rs-599484/v1 ◽

2021 ◽

Author(s):

Junwei Zou ◽

Yong Huang ◽

Zhaoying Wu ◽

Hao Xie ◽

Rongsheng Wang ◽

...

Keyword(s):

Overall Survival ◽

Rna Splicing ◽

Rna Binding ◽

The Cancer Genome Atlas ◽

Prognostic Indicators ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Stomach Adenocarcinoma ◽

Tumor Pathogenesis ◽

Kaplan Meier Plotter

Abstract Stomach adenocarcinoma(STAD) is one of the deadliest cancers in the world. The expression levels of family members of mex-3 RNA that bound MEX3A (member A) and MEX3B (member B) were high expressions in different cancers and interconnected to deficient prognosis. The present research assessed the potential regarding the expression of MEX3A and MEX3B in STAD by analysing the facts of STAD (viz. The Cancer Genome Atlas). TCGA, MEX3A and MEX3B in the cancers were analyzed using TIMER2.0, Kaplan Meier Plotter, and cBioPortal. The data was visualized using version 4.0.3 of R. We found MEX3A and MEX3B had various expressions regarding major cancer and relevant common tissues. Especially, high expression of MEX3A and MEX3B had relationships with the OS (namely overall survival) with deficiency and RFS (viz. relapse-free survival) concerning STAD. The expressions of MEX3B had correlations to T stage with P being 0.012 and to the race with P being 0.049. MEX3B was highly expressed in T3 and T4 stages, and was highly expressed in the white race. MEX3A mutation had a better survival without diseases, with P being 0.0205. However, the situation was different with non-overall survival, with P being 0.194, in comparison with the patients who did not have MEX3A change. MEX3A and MEX3B on tumor pathogenesis might be related to "RNA splicing" and "spliceosomal complex" and "single-stranded RNA binding". We further investigated the association between MEX3A and MEX3B and immune cells. The mast cells of the most connections to MEX3A (R=-0.300, P<0.001) and the NK cells were positively correlation with MEX3B (R=0.590, P<0.001). It showed that they might be potential prognostic molecular biomarkers in patients with STAD.

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Identification of ST7 Alteration Profile, Frequency of Alteration and Correlation with ST7-Related Genes using TCGA Data

Walailak Journal of Science and Technology (WJST) ◽

10.48048/wjst.2019.6226 ◽

2019 ◽

Vol 16 (3) ◽

pp. 217-230

Author(s):

Nurdina CHARONG ◽

Moltira PROMKAN

Keyword(s):

Disease Free Survival ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Free Survival ◽

Cancer Genome Atlas ◽

Stomach Adenocarcinoma ◽

Using Data ◽

Liver Hepatocellular Carcinoma ◽

Disease Free ◽

Genome Atlas

ST7 (Suppression of Tumorigenicity 7) was reported as a protein playing a role in maintaining cellular structure. This study aims to investigate the ST7 alteration profiles and frequency of alteration in different cancers using data from The Cancer Genome Atlas (TCGA). The correlation between alterations of ST7 and angiogenesis-related genes, SERPINE1, MMP13, and VEGFA, was determined and the relation between ST7 and genes involved in suppression of ST7 transcription, PRMT5 and SMARCA4, were also analyzed. Data of 6 cancer groups from The Cancer Genome Atlas (TCGA) including ovarian serous cystadenocarcinoma (OSC), liver hepatocellular carcinoma (LHC), bladder urothelial adenocarcinoma (BUA), stomach adenocarcinoma (SC), prostate adenocarcinoma (PRAD) and glioblastoma multiforme (GBM) were downloaded for this study. The results indicated that 3 alteration patterns including amplification, missense mutation, and deletion were observed in 6 cancer studies. Gene pair between ST7 and SERPINE1 indicated the co-occurrent alteration in BUC, OSC and SC (p < 0.05). However, no association between alterations of these 2 genes and survival events in our study was observed. Shorter overall survival rate and disease-free survival were found in BUC patients with ST7, PRMT5, and SMARCA4 alterations. These findings suggest that using TCGA data can target the potential genes involved in carcinogenesis. Combining ST7 with PRMT5 and SMARCA4 could be used as indicators for analyzing the patient survival in BUC patients and may serve as the potential therapeutic target for cancer in the future.

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Comprehensive Analysis of m6A Regulators Characterized by the Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma to Aid Immunotherapy and Chemotherapy

Frontiers in Oncology ◽

10.3389/fonc.2021.764798 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhiqiang Yang ◽

Xiaoping Ming ◽

Shuo Huang ◽

Minlan Yang ◽

Xuhong Zhou ◽

...

Keyword(s):

Overall Survival ◽

Immune Cell ◽

Comprehensive Evaluation ◽

Principal Component ◽

Response To Therapy ◽

The Cancer Genome Atlas ◽

Mutation Burden ◽

Number Variation ◽

Clinical Benefits ◽

Cancer Genome Atlas

BackgroundN6-Methyladenosine (m6A), which is a prevalent regulator of mRNA expression, has gathered increasing study interests. Though the role of m6A as being important in many biological processes (such as growth and proliferation of cancers) has been well documented, its potential role in tumor immune microenvironment (TIME) has rarely been analyzed.MethodsWe downloaded RNA expression, single nucleotide polymorphism (SNP), and copy number variation (CNV) data from The Cancer Genome Atlas (TCGA). We then curated 21 m6A regulators and clustered patients into three m6A subtypes and m6A-related gene subtypes and compared them based on overall survival (OS). The combination of CIBERSORT as well as ssGSEA quantified the infiltration levels of immune cells and immune-related functions. The m6A scores were determined by using principal component analysis (PCA) algorithm. Furthermore, we evaluate the correlation of m6A regulators with immune and response to therapy.ResultsThree m6A clusters were identified based on the TCGA-HNSCC cohort, and there were significant associations among them in overall outcomes and caner-related pathways. We found that three m6A clusters were consistent with three phenotypes: immune-inflamed, immune-dessert, and immune-excluded. HNSCC patients were divided into high– and low–m6A score groups based on the cutoff of m6A score. Patients with lower m6A score had better overall survival outcome. Further analysis indicated that patients with higher m6A score presented higher tumor mutation burden (TMB). In addition, patients in low–m6A score subgroup had high chemotherapeutics sensitivity. GEO cohort confirmed patients with low m6A score demonstrated significant overall survival advantages and clinical benefits. Low m6A score carry an increased neoantigen load, eliciting a response to immunotherapy, and its value in predicting survival outcomes of immunotherapy was also confirmed in three anti-PD-1 cohorts.ConclusionsOur study demonstrated that m6A regulators are closely related to TIME and the m6A score was an effective prognostic biomarker and predictive indicator for immunotherapy and chemotherapeutics. Comprehensive evaluation of m6A regulators in tumors will extend our understanding of TIME and effectively guide increasing study investigations on immunotherapy and chemotherapy strategies for HNSCC.

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The prognostic value of faciogenital dysplasias as biomarkers in head and neck squamous cell carcinoma

Biomarkers in Medicine ◽

10.2217/bmm-2019-0273 ◽

2019 ◽

Vol 13 (16) ◽

pp. 1399-1415 ◽

Cited By ~ 1

Author(s):

Chao Ma ◽

Haoyu Li ◽

Xian Li ◽

Shuwen Lu ◽

Jianfeng He

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prognostic Value ◽

The Cancer Genome Atlas ◽

Gene Expressions ◽

Cancer Genome Atlas ◽

Genome Atlas

Aim: This present study aims to investigate the prognostic value of FGD genes for predicting the overall survival in head and neck squamous cell carcinoma (HNSC) patients. Materials & methods: Clinical information and FGD gene expressions of 513 HNSC patients were obtained from The Cancer Genome Atlas dataset. Kaplan–Meier survival, Pearson correlation coefficient analyses and enrichment analyses were performed based on The Cancer Genome Atlas dataset, as well as FGD gene expressions analysis in normal tissues. Results: The survival analyses showed that high levels of FGD2 and FGD3 mRNA expressions, and the combination of high levels of FGD2 and FGD3 mRNAs were associated with the favorable overall survival in HNSC patients (p < 0.01). Oppositely, no significant correlations (p > 0.05) were observed between gender and race and OS. Conclusion: Our findings suggest that the expression levels of FGD2 and FGD3 mRNAs in HNSC are associated with favorable prognosis and may be regarded as potential prognostic biomarkers.

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Distinctive Expression and Amplification of Genes at 11q13 in Relation to HPV Status with Impact on Survival in Head and Neck Cancer Patients

Journal of Clinical Medicine ◽

10.3390/jcm7120501 ◽

2018 ◽

Vol 7 (12) ◽

pp. 501 ◽

Cited By ~ 6

Author(s):

Francisco Hermida-Prado ◽

Sofía Menéndez ◽

Pablo Albornoz-Afanasiev ◽

Rocío Granda-Diaz ◽

Saúl Álvarez-Teijeiro ◽

...

Keyword(s):

Protein Expression ◽

Head And Neck ◽

Gene Amplification ◽

Hpv Infection ◽

The Cancer Genome Atlas ◽

Hpv Status ◽

The Status ◽

Impact On Survival ◽

Cancer Genome Atlas ◽

The Impact

Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the CTTN, CCND1 and ANO1 genes mapping at the 11q13 amplicon in relation to the HPV status in HNSCC patients. CTTN, CCND1 and ANO1 protein expression and gene amplification were respectively analyzed by immunohistochemistry and real-time PCR in a homogeneous cohort of 392 surgically treated HNSCC patients. The results were further confirmed using an independent cohort of 279 HNSCC patients from The Cancer Genome Atlas (TCGA). The impact on patient survival was also evaluated. CTTN, CCND1 and ANO1 gene amplification and protein expression were frequent in HPV-negative tumors, while absent or rare in HPV-positive tumors. Using an independent validation cohort of 279 HNSCC patients, we consistently found that these three genes were frequently co-amplified (28%) and overexpressed (39–46%) in HPV-negative tumors, whereas almost absent in HPV-positive tumors. Remarkably, these alterations (in particular CTTN and ANO1 overexpression) were associated with poor prognosis. Taken together, the distinctive expression and amplification of these genes could cooperatively contribute to the differences in prognosis and clinical outcome between HPV-positive and HPV-negative tumors. These findings could serve as the basis to design more personalized therapeutic strategies for HNSCC patients.

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Deep Learning for Automatic Subclassification of Gastric Carcinoma Using Whole-Slide Histopathology Images

Cancers ◽

10.3390/cancers13153811 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3811

Author(s):

Hyun-Jong Jang ◽

In-Hye Song ◽

Sung-Hak Lee

Keyword(s):

Deep Learning ◽

Relative Proportion ◽

The Cancer Genome Atlas ◽

Cancer Tissue ◽

Mucinous Tumor ◽

Receiver Operating Characteristic Curves ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Stomach Adenocarcinoma ◽

Tumor Types

Histomorphologic types of gastric cancer (GC) have significant prognostic values that should be considered during treatment planning. Because the thorough quantitative review of a tissue slide is a laborious task for pathologists, deep learning (DL) can be a useful tool to support pathologic workflow. In the present study, a fully automated approach was applied to distinguish differentiated/undifferentiated and non-mucinous/mucinous tumor types in GC tissue whole-slide images from The Cancer Genome Atlas (TCGA) stomach adenocarcinoma dataset (TCGA-STAD). By classifying small patches of tissue images into differentiated/undifferentiated and non-mucinous/mucinous tumor tissues, the relative proportion of GC tissue subtypes can be easily quantified. Furthermore, the distribution of different tissue subtypes can be clearly visualized. The patch-level areas under the curves for the receiver operating characteristic curves for the differentiated/undifferentiated and non-mucinous/mucinous classifiers were 0.932 and 0.979, respectively. We also validated the classifiers on our own GC datasets and confirmed that the generalizability of the classifiers is excellent. The results indicate that the DL-based tissue classifier could be a useful tool for the quantitative analysis of cancer tissue slides. By combining DL-based classifiers for various molecular and morphologic variations in tissue slides, the heterogeneity of tumor tissues can be unveiled more efficiently.

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Predicted CD4+ T cell infiltration levels could indicate better overall survival in sarcoma patients

Journal of International Medical Research ◽

10.1177/0300060520981539 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052098153

Author(s):

Qing Bi ◽

Yang Liu ◽

Tao Yuan ◽

Huizhen Wang ◽

Bin Li ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Survival Data ◽

Tumor Infiltrating Lymphocytes ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

T Cell Infiltration ◽

Whole Exome ◽

Cancer Genome Atlas ◽

Infiltrating Lymphocytes

Objective The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. Methods Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. Results Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. Conclusions This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.

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Phase II Evaluation of Sorafenib in Advanced and Metastatic Squamous Cell Carcinoma of the Head and Neck: Southwest Oncology Group Study S0420

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.6834 ◽

2010 ◽

Vol 28 (20) ◽

pp. 3330-3335 ◽

Cited By ~ 82

Author(s):

Stephen K. Williamson ◽

James Moon ◽

Chao H. Huang ◽

Perry P. Guaglianone ◽

Michael LeBlanc ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Adverse Events ◽

Cell Carcinoma ◽

Head And Neck ◽

Phase Ii ◽

Single Agent ◽

Response Probability ◽

Oncology Group ◽

Southwest Oncology Group

Purpose We conducted a phase II trial to evaluate the efficacy and safety of single-agent sorafenib in chemotherapy-naïve patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). The primary end point was response probability (ie, confirmed complete and partial response [PR]). Patients and Methods Chemotherapy-naïve patients with metastatic, persistent, or recurrent SCCHN who received one induction or fewer or received an adjuvant chemotherapy regimen, who had adequate organ function, and who had a performance status ≤ 1 were eligible. Sorafenib was administered orally at 400 mg twice daily on a continuous basis in 28-day cycles. Responses were evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors). Results Sorafenib was generally well tolerated. Of the 41 eligible patients assessed for adverse events, one experienced a grade 4 adverse event as a result of an asymptomatic pulmonary embolus. The most common grades 2 to 3 adverse events were fatigue, anorexia, stomatitis/oral pain, abdominal pain, hand-foot syndrome, weight loss, and hypertension. There was one confirmed PR and two unconfirmed PRs. The estimated confirmed response probability was 2% (95% CI, 0% to 13%). The estimated median progression-free survival was 4 months (95% CI, 2 to 4 months), and the estimated median overall survival was 9 months (95% CI, 7 to 14 months). Conclusion Sorafenib was well tolerated. Although response was poor, progression-free and overall survival times compare favorably with previous Southwest Oncology Group, phase II, single-agent trials.

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Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer

Future Oncology ◽

10.2217/fon-2020-1163 ◽

2021 ◽

Author(s):

Xiao-Cheng Wang ◽

Ya Liu ◽

Fei-Wu Long ◽

Liang-Ren Liu ◽

Chuan-Wen Fan

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Markers ◽

The Cancer Genome Atlas ◽

Prognostic Signature ◽

Free Survival ◽

Cancer Genome Atlas ◽

Bioinformatic Approaches ◽

Cell Phenotypes ◽

The Relationship

Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

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