Dataset Information

Retrospective Study on Epidemiology of Colorectal Lesions

ABSTRACT: Retrospective analysis on colonoscopies in the endoscopy unit of the Lyell McEwin Hospital.

DISEASE(S): Colonic Polyps,Colorectal Cancer,Colonic Polyp,Colonic Neoplasms

PROVIDER: 2235314 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Background: Colorectal liver metastases (CRLM) are the leading cause of colorectal cancer (CRC)-related mortality. Transfer RNA-derived fragments (tRFs), a novel class of small non-coding RNAs (sncRNA), regulate gene expression, stress response, and immune functions in cancer. While tRFs are increasingly implicated in CRC progression, their prognostic significance in CRLM remains unknown. This study investigates the abundance and prognostic value of genomic (ge) and mitochondrial (mt) tRFs in CRLM. Methods: This single-center retrospective cohort study included all CRLM patients who underwent curative liver resection between January 2012 and December 2015. Small RNA sequencing (sRNA-seq) quantified ge- and mt-tRF expression in tumor samples. Event-free survival (EFS) was the primary outcome, and the impact of tRFs on EFS was assessed using Cox regression, spline modeling of the effects of tRFs on EFS, and network analysis. Results: Among 588 screened samples, 40 met eligibility criteria (18 females [45%], median age 64 [42-79]). A total of 432 tRFs were identified, with ge-tRFs (67%) being more abundant than mt-tRFs (33%). Using spline regressions, tRFs were classified into 10 ten prognostic groups. High ge-tRF abundance correlated predominantly with unfavorable EFS (FDR<0.2; 94%), whereas mt-tRFs were significantly (p<0.001; χ2 test) more often associated with favorable EFS (FDR<0.2; 26%). Network analysis of tRF abundance correlations revealed a significantly higher intra-mitochondrial network density compared to the intra-genomic tRF network. However, no significant differences in network structure were observed between prognostically significant vs. non-significant or favorable vs. unfavorable tRFs. Finally, key tRF candidates, such as tRHalve3-His-CAU (mt-tRF) or tRNAleader-Gln-UUG (mt-tRF) paired with tRFmisc-Tyr-GTA (ge-tRF), remained independent prognostic markers after adjustment for clinical covariates. Conclusion: This study provides the first comprehensive characterization of tRF expression in CRLM, revealing distinct prognostic roles for ge- and mt-tRFs. While ge-tRFs were predominantly associated with unfavorable prognosis, a subset of mt-tRFs demonstrated a favorable impact on EFS. These findings highlight the potential of tRFs as novel prognostic biomarkers and therapeutic targets in CRLM, warranting validation in prospective studies.

Project description:Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development. Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n=29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n=35) consisted of a random sample of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. miRNA profiling was performed using formalin-fixed, paraffin-embedded tumors. Biomarkers related to metastatic potential were identified independent of clinical stage, and a cutoff point was selected based on the optimal sensitivity and specificity (ROC curve). Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. Results: miRNA expression profiling identified several miRNAs that were either specific and shared across all clinical stages (p?0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family), cell proliferation and invasion (hsa-miR-16 and has-miR-205) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were up-regulated in metastatic cases of CSI and II. Furthermore, the combination of the 3 miRNAs identified for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.

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Retrospective Study on Epidemiology of Colorectal Lesions

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