A nineteen gene‐based risk score classifier predicts prognosis of colorectal cancer patients

Abstract

Colorectal cancer (CRC) patients frequently experience disease recurrence and distant metastasis. This study aimed to identify prognostic indicators, including individual responses to chemotherapy, in CRC patients. RNA-seq data was generated using 54 samples (normal colon, primary CRC, and liver metastases) from 18 CRC patients and genes associated with CRC aggressiveness were identified. A risk score based on these genes was developed and validated in four independent CRC patient cohorts (n = 1063). Diverse statistical methods were applied to validate the risk scoring system, including a generalized linear model likelihood ratio test, Kaplan-Meier curves, a log-rank test, and the Cox model. TREM1 and CTGF were identified as two activated regulators associated with CRC aggressiveness. A risk score based on 19 genes regulated by TREM1 or CTGF activation (TCA19) was a significant prognostic indicator. In multivariate and subset analyses based on pathological staging, TCA19 was an independent risk factor (HR = 1.894, 95% CI = 1.227-2.809, P = 0.002). Subset stratification in stage III patients revealed that TCA19 had prognostic potential and identified patients who would benefit from adjuvant chemotherapy, regardless of age. The TCA19 predictor represents a novel diagnostic tool for identifying high-risk CRC patients and possibly predicting the response to adjuvant chemotherapy.

PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis

“…In 70 samples, PKLR mRNA was significantly upregulated in liver metastases relative to primary tumors ( Figure 3A). This upregulation was also observed in multiple independent data sets of unmatched ( Figure 3, B and C) and matched ( Figure 3, D and E) samples from patients with colorectal cancer (24)(25)(26)(27). These samples were from a total of 311 patients.…”

“…GCLC, the rate-limiting enzyme in glutathione synthesis, promotes liver metastatic colonization. (A and B) GCLC expression as measured in (A) unmatched (27) and (B) matched primary and liver metastasis tumor samples (24). Increased GCLC expression is indicated in red; decreased expression is indicated in gray.…”

Transcriptome and long noncoding RNA sequencing of three extracellular vesicle subtypes released from the human colon cancer LIM1863 cell line

“…We used two CRC gene expression studies (SRP02205476 and SRP02988077) from the SRA database (https://www.ncbi.nlm.nih.gov/Traces/sra/sra.cg) - 4 and 18 pairs of tumour/normal tissues from CRC patients, respectively - to validate the expression levels of candidate mRNAs and lncRNAs found in our study. Heat maps for these two studies (Supplementary Fig.…”

Andrographolide suppresses proliferation of human colon cancer SW620 cells through the TLR4/NF-κB/MMP-9 signaling pathway

“…In recent years, with changes in dietary patterns, the morbidity and mortality rates of colon cancer have significantly increased (1). In cancer progression, the invasion and metastasis of colon cancer markedly affects the prognosis of colon cancer patients and is a common leading cause of cancer-associated mortality (2). The metastasis and infiltration of cancer are associated with various factors.…”