Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases

The main goal of this study is to consider SLC34A2 as a potential prognostic marker of oncological diseases using the mutational, expression, and survival data of cancer studies which are publicly available online. We collected data from four databases (cBioPortal, The Cancer Genome Atlas; cBioPortal, Genie; International Cancer Genome Consortium; ArrayExpress). In total, 111,283 samples were categorized according to 27 tumor locations. Ninety-nine functionally significant missense mutations and twelve functionally significant indel mutations in SLC34A2 were found. The most frequent mutations were SLC34A2-ROS1, p.T154A, p.P506S/R/L, p.G257A/E/R, p.S318W, p.A396T, p.P410L/S/H, p.S461C, p.A473T/V, and p.Y503H/C/F. The upregulation of SLC34A2 was found in samples of myeloid, bowel, ovarian, and uterine tumors; downregulation was found in tumor samples of breast, liver, lung, and skin cancer tumors. It was found that the life expectancy of breast and thymus cancer patients with an SLC34A2 mutation is lower, and it was revealed that SLC34A2 overexpression reduced the life span of patients with brain, ovarian, and pancreatic tumors. Thereby, for these types of oncological diseases, the mutational profile of SLC34A2 can be a potential prognostic marker for breast and thymus cancers, and the upregulation of SLC34A2 can be a potential prognostic marker for brain, ovarian, and pancreatic cancers.

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The Biological Function Delineated Across Pan-Cancer Levels Through lncRNA-Based Prognostic Risk Assessment Factors for Pancreatic Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.694652 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xudong Tang ◽

Mengyan Zhang ◽

Liang Sun ◽

Fengyan Xu ◽

Xin Peng ◽

...

Keyword(s):

Pancreatic Cancer ◽

Prognostic Marker ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Research Network ◽

Molecular Characteristics ◽

Cancer Data ◽

Cancer Genome Atlas ◽

Pan Cancer ◽

Genome Atlas

Long non-coding RNAs (lncRNAs) play key roles in tumors and function not only as important molecular markers for cancer prognosis, but also as molecular characteristics at the pan-cancer level. Because of the poor prognosis of pancreatic cancer, accurate assessment of prognosis is a key issue in the development of treatment plans for pancreatic cancer. Here we analyzed pancreatic cancer data from The Cancer Genome Atlas and The Genotype Tissue Expression database using Cox regression and lasso regression in analyses using a combination of the two databases as well as only The Cancer Genome Atlas database (Cancer Genome Atlas Research Network et al., 2013). A prognostic risk score model with significant correlation with pancreatic cancer survival was constructed, and two lncRNAs were investigated. Additional analysis of 33 cancers using the two lncRNAs showed that lncRNA TsPOAP1-AS1 was a prognostic marker of seven cancers, among which pancreatic cancer was the most significant, and lncRNA mi600hg was a prognostic marker of ovarian cancer and pancreatic cancer. LncRNA TsPOAP1-AS1 is associated with clinical stage and tumor mutation burden of some cancers as well as a strong degree of immune infiltration in many cancers, while a strong correlation between lncRNA mi600hg and microsatellite instability was observed in several cancers. The results of this study help further our understanding of the different functions of lncRNAs in cancer and may aid in the clinical application of lncRNAs as prognostic factors for cancer.

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Indoleamine 2,3-dioxygenase (IDO1), PD-L1, and overall survival (OS) of patients diagnosed with esophageal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.50 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 50-50 ◽

Cited By ~ 1

Author(s):

Ari Rosenberg ◽

Derek Wainwright ◽

Alfred Rademaker ◽

Carlos Galvez ◽

Matthew Genet ◽

...

Keyword(s):

Esophageal Cancer ◽

Survival Data ◽

Human Cancer ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Mrna Levels ◽

Exact Test ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Genome Atlas

50 Background: Immune checkpoint inhibition of PD-L1 is emerging as an important therapeutic target for patients with advanced esophageal cancer. However, response rates to therapy remain low. IDO1 is a rate-limiting immunosuppressive enzyme that has emerged as an important immunotherapeutic target in human cancer. The role, expression pattern, and relevance of IDO1 in esophageal cancer are currently unknown. Here, we utilize gene expression analysis of the cancer genome atlas and quantitative immunohistochemistry (IHC) to understand whether IDO1 contributes to a poor esophageal cancer patient prognosis. Methods: mRNA expression was assessed using Hi-RNA sequencing in an esophageal squamous cell carcinoma (SCC) cohort of 87 patients and an adenocarcinoma (AC) cohort of 97 patients. Survival data was obtained from the Cancer Genome Atlas. Patient survival was analyzed by the Kaplan-Meier Method. IHC for a second cohort of 93 cases of esophageal SCC were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic immunoscoring analysis. Correlation between markers was analyzed using Fisher’s exact test. Results: The median OS for high versus low IDO1 mRNA levels was 15.9 months vs 41.5 months, respectively (p =0.02) in the SCC cohort. The median OS was 20.1 months and 58.6 months in the high vs low IDO1 mRNA levels, respectively (p = 0.036) in the esophageal AC cohort. High co-expression for IDO1 and PD-L1 vs low co-expression of these markers, demonstrated a median OS of 15.1 months and 41.5 months, respectively, in the SCC cohort, and 13.7 months and 41.5 months, respectively, in the AC cohort. IHC for IDO1 SCC showed a significant correlation with PD-L1 (p = < 0.0001) and CD3ε (p = < 0.0001). PD-L1 expression also significantly correlated with CD3ε expression (p = < 0.0001). Conclusions: Esophageal cancer with high IDO1 and PD-L1 levels is associated with significantly decreased survival. The expression of IDO1 and PD-L1 is significantly enhanced by the coincident intratumoral increase of T cells. These data suggest that combinatorial approaches for combination therapies that simultaneously inhibit IDO1 and PD-(L)1 may enhance T-cell mediated control of esophageal cancer in patients.

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Does HPV Subtype Predict Outcomes in Head and Neck Cancers?

International Journal of Otolaryngology ◽

10.1155/2021/6672373 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Hedyeh Ziai ◽

Andrew Warner ◽

Neil Mundi ◽

Krupal Patel ◽

Eun Jae Chung ◽

...

Keyword(s):

Head And Neck ◽

Survival Data ◽

Quantitative Polymerase Chain Reaction ◽

Cancer Genome ◽

Head And Neck Cancers ◽

The Cancer Genome Atlas ◽

Hpv 16 ◽

Hpv Genotypes ◽

Cancer Genome Atlas ◽

Genome Atlas

Background. Recently, reanalysis of The Cancer Genome Atlas study demonstrated that human papillomavirus (HPV) genotypes in head and neck cancers other than HPV-16 have inferior survival to HPV-16-positive tumors. We aimed to examine the association of HPV subtypes and survival in a large cohort of patient samples from our institution. Methods. Fresh frozen primary site biopsy samples were collected either in clinic or at the time of surgery. Patient demographic, staging, and survival data were also collected. Tumors were tested for HPV subtypes by quantitative polymerase chain reaction (qPCR). Univariable and multivariable analyses were performed using Cox proportional hazards regression. Results. 280 patient biopsy samples were collected between 2011 and 2017. Mean ± standard deviation (SD) age was 61.9 ± 11.1 years and most patients (78%) were male. The majority of cancers were of the oral cavity (60%) or oropharynx (25%) and 30% had HPV-positive disease. Median follow-up was 3.76 years and 96/280 patients (34%) developed recurrences. Patients with p16-positive versus negative disease had significantly improved 5-year overall survival (OS, 77.6% vs. 53.3%; p = 0.009 ) and progression-free survival (PFS, 67.3% vs. 41.0%, p = 0.006 ). Similarly improved 5-year OS and PFS were observed for patients with HPV-positive versus negative disease (65.0% vs. 55.0%, p = 0.084 ; 53.3% vs. 43.2%, p = 0.072 , resp.). Patients with HPV-16 compared to other HPV diseases had worse 5-year OS and PFS (62.1% vs. 88.9%, p = 0.273 ; 49.0% vs. 88.9%, p = 0.081 , resp.). Conclusions. In contrast to the data derived from The Cancer Genome Atlas, patients with HPV-16 tumors trended towards decreased PFS and OS compared with tumors driven by other HPV genotypes. Further larger multi-institutional studies are necessary to understand the relationship between other HPV genotypes and survival in head and neck squamous cell carcinomas.

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Special Report: The Cancer Genome Atlas Begins with 3-Year, $100 Million Pilot

PsycEXTRA Dataset ◽

10.1037/e481292006-009 ◽

2005 ◽

Author(s):

Keyword(s):

Cancer Genome ◽

The Cancer Genome Atlas ◽

Special Report ◽

Cancer Genome Atlas ◽

Genome Atlas

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Differences in endometrial cancer molecular portraits based on ethnicity in The Cancer Genome Atlas

10.26226/morressier.59ba7298d462b80296ca20c6 ◽

2017 ◽

Author(s):

David Guttery

Keyword(s):

Endometrial Cancer ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Genome Atlas

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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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Exceptional Chemotherapy Response in Metastatic Colorectal Cancer Associated With Hyper-Indel–Hypermutated Cancer Genome and Comutation of POLD1 and MLH1

JCO Precision Oncology ◽

10.1200/po.16.00015 ◽

2017 ◽

pp. 1-12

Author(s):

Manish R. Sharma ◽

James T. Auman ◽

Nirali M. Patel ◽

Juneko E. Grilley-Olson ◽

Xiaobei Zhao ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Somatic Mutation ◽

Mutation Rate ◽

Germ Line ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Response To Chemotherapy ◽

Cancer Genome Atlas ◽

Genome Atlas

Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years. We sequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients with POLE- and/or POLD1-mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G>A [p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel–hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy.

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