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L1TD1 - a prognostic marker for colon cancer.

ABSTRACT: BACKGROUND:Prognostic markers specific to a particular cancer type can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities. METHODS:Gene expression data was analyzed from three independent colon cancer microarray gene expression data sets (N?=?1052). Survival analysis was performed for the three data sets, stratified by the expression level of the LINE-1 type transposase domain containing 1 (L1TD1). Correlation analysis was performed to investigate the role of the interactome of L1TD1 in colon cancer patients. RESULTS:We found L1TD1 as a novel positive prognostic marker for colon cancer. Increased expression of L1TD1 associated with longer disease-free survival in all the three data sets. Our results were in contrast to a previous study on medulloblastoma, where high expression of L1TD1 was linked with poor prognosis. Notably, in medulloblastoma L1TD1 was co-expressed with its interaction partners, whereas our analysis revealed lack of co-expression of L1TD1 with its interaction partners in colon cancer. CONCLUSIONS:Our results identify increased expression of L1TD1 as a prognostic marker predicting longer disease-free survival in colon cancer patients.

SUBMITTER: Chakroborty D

PROVIDER: S-EPMC6651905 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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L1TD1 - a prognostic marker for colon cancer.

Chakroborty Deepankar D Emani Maheswara Reddy MR Klén Riku R Böckelman Camilla C Hagström Jaana J Haglund Caj C Ristimäki Ari A Lahesmaa Riitta R Elo Laura L LL

BMC cancer 20190723 1

<h4>Background</h4>Prognostic markers specific to a particular cancer type can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities.<h4>Methods</h4>Gene expression data was analyzed from three independent colon cancer microarray gene expression data sets (N = 1052). Survival analysis was performed for the three data sets, stratified by the expression level of the LINE-1 type transposase domain containing 1 (L1TD1). Correlat ...[more]

PMID: 31337362

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Project description:Colon cancer (CC) is one of the most commonly diagnosed tumours worldwide. Single-cell RNA sequencing (scRNA-seq) can accurately reflect the heterogeneity within and between tumour cells and identify important genes associated with cancer development and growth. In this study, scRNA-seq was used to identify reliable prognostic biomarkers in CC. ScRNA-seq data of CC before and after 5-fluorouracil treatment were first downloaded from the Gene Expression Omnibus database. The data were pre-processed, and dimensionality reduction was performed using principal component analysis and t-distributed stochastic neighbour embedding algorithms. Additionally, the transcriptome data, somatic variant data, and clinical reports of patients with CC were obtained from The Cancer Genome Atlas database. Seven key genes were identified using Cox regression analysis and the least absolute shrinkage and selection operator method to establish signatures associated with CC prognoses. The identified signatures were validated on independent datasets, and somatic mutations and potential oncogenic pathways were further explored. Based on these features, gene signatures, and other clinical variables, a more effective predictive model nomogram for patients with CC was constructed, and a decision curve analysis was performed to assess the utility of the nomogram. A prognostic signature consisting of seven prognostic-related genes, including CAV2, EREG, NGFRAP1, WBSCR22, SPINT2, CCDC28A, and BCL10, was constructed and validated. The proficiency and credibility of the signature were verified in both internal and external datasets, and the results showed that the seven-gene signature could effectively predict the prognosis of patients with CC under various clinical conditions. A nomogram was then constructed based on features such as the RiskScore, patients' age, neoplasm stage, and tumor (T), nodes (N), and metastases (M) classification, and the nomogram had good clinical utility. Higher RiskScores were associated with a higher tumour mutational burden, which was confirmed to be a prognostic risk factor. Gene set enrichment analysis showed that high-score groups were enriched in 'cytoplasmic DNA sensing', 'Extracellular matrix receptor interactions', and 'focal adhesion', and low-score groups were enriched in 'natural killer cell-mediated cytotoxicity', and 'T-cell receptor signalling pathways', among other pathways. A robust seven-gene marker for CC was identified based on scRNA-seq data and was validated in multiple independent cohort studies. These findings provide a new potential marker to predict the prognosis of patients with CC.

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L1TD1 - a prognostic marker for colon cancer.

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L1TD1 - a prognostic marker for colon cancer.

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