Recent studies have revealed the Glasgow prognostic score (GPS) to aid in the prediction of postoperative outcome in colorectal cancer patients. However, whether GPS predicts poor prognosis in curative colorectal cancer patients has yet to be ascertained. Furthermore, there is no information on the association between GPS and adjuvant chemotherapy in stage II or III colorectal cancer patients. A total of 219 patients with stage II and III colorectal cancer were included in this trial. The modified GPS (mGPS) defined in this study was calculated on the basis of admission data as follows: patients with an elevated level of both C-reactive protein (0.5 mg/dl) and hypoalbuminemia (Alb <3.5 mg/dl) were allocated a score of 2, and patients showing 1 or none of these blood chemistry abnormalities were allocated a score of 1 or 0, respectively. The association between the mGPS and clinicopathological findings and survival was retrospectively assessed. The mGPS was significantly higher in patients with an advanced age, serosal invasion, advanced stage cancer and pre-operative high CEA levels. Kaplan-Meier analysis revealed that a higher GPS predicted a higher risk of postoperative mortality in stage II and/or III colorectal cancer patients. Multivariate analyses revealed that the mGPS was the most sensitive predictor of postoperative mortality in stage II/III or stage II, respectively. The prognosis of stage II patients with a higher mGPS was as favorable as that of patients with a lower mGPS when adjuvant chemotherapy was undertaken. Pre-operative mGPS is considered to be a useful predictor of postoperative mortality in patients with stage II and/or III colorectal cancer, independently of the CEA test or TNM system. Postoperative adjuvant chemotherapy may be recommended for stage II colorectal cancer patients with a high mGPS.

Slug and Vimentin genes play a critical role in regulating epithelial–mesenchymal transition (EMT) via downregulation of epithelial markers and upregulation of mesenchymal markers. The present study evaluated the clinical significance of Slug and Vimentin expression as potential disease biomarkers in colorectal cancer (CRC). At first, the biological role of Slug in CRC was assessed by RNA interference in CRC cell lines to assess tumor progression, invasion and migration. Next, we analyzed Slug and Vimentin expression in surgical tissue specimens from 181 CRC patients (Cohort 1) by quantitative real-time reverse transcription–PCR and 208 patients (Cohort 2) by immunohistochemistry. Knockdown of Slug using small interfering RNA in CRC cell lines resulted in inhibition of EMT, reduced cell proliferation, invasion and migration in CRC cells. Interestingly, Slug and Vimentin expression in cancer tissues was significantly higher in patients with higher T stage, lymph node involvement, liver metastasis and advanced tumor node metastasis stages. A significant correlation was observed between Slug and Vimentin expression in CRC (messenger RNA: ρ = 0.546, protein: ρ = 0.405), and increased expression of Slug and Vimentin was significantly associated with poor prognosis. Furthermore, increased expression of Slug emerged as an independent prognostic factor and a predictive marker of lymph node metastasis in CRC patients. Our data provide novel evidence for the biological and clinical significance of Slug and Vimentin expression as potential predictive biomarkers for identifying patients with lymph node metastasis or poor prognosis in CRC.

Background Circulating microRNAs (miRNAs) are attracting major interest as potential noninvasive biomarkers for colorectal cancer (CRC). This study aimed to identify a novel serum miRNA biomarker for the early detection and/or evaluating prognosis of CRC patients. Patients and methods Comprehensive miRNA array analysis was performed using serum samples from patients with colorectal neoplasia and healthy controls. Next, to verify whether the candidate miRNA possessed a secretory potential, we screened miRNA expression levels in culture medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12 adenoma and 12 control subjects. Thereafter, we validated expression of candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects. Results Through microarray analysis, we identified significantly higher levels of miRNA-1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We verified miR-1290 overexpression in serum of CRC patients in a training cohort. In the validation cohort, serum miR-1290 levels were significantly upregulated in patients with colorectal adenomas (P<0.0001) and cancers (P<0.0001). Serum miR-1290 levels could robustly distinguish adenoma (area under the curve [AUC]=0.718) and CRC patients (AUC=0.830) from normal subjects. High miR-1290 expression in serum and tissue was significantly associated with tumor aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an independent prognostic factor (hazard ratio=4.51; 95% confidence interval=1.23-23.69; P=0.0096) and an independent predictor for tumor recurrence (hazard ratio=3.92; 95% confidence interval=1.11-25.14; P=0.032) in CRC. Conclusions Serum miR-1290 is a novel biomarker for early detection, recurrence and prognosis in CRC.

Adenosine-to-inosine (A-to-I) RNA editing, a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family, is a recently discovered epigenetic modification dysregulated in human cancers. However, the clinical significance and the functional role of RNA editing in colorectal cancer (CRC) remain unclear. We have systematically and comprehensively investigated the significance of the expression status of ADAR1 and of the RNA editing levels of antizyme inhibitor 1 (AZIN1 ), one of the most frequently edited genes in cancers, in 392 colorectal tissues from multiple independent CRC patient cohorts. Both ADAR1 expression and AZIN1 RNA editing levels were significantly elevated in CRC tissues when compared with corresponding normal mucosa. High levels of AZIN1 RNA editing emerged as a prognostic factor for overall survival and disease-free survival and were an independent risk factor for lymph node and distant metastasis. Furthermore, elevated AZIN1 editing identified high-risk stage II CRC patients. Mechanistically, edited AZIN1 enhances stemness and appears to drive the metastatic processes. We have demonstrated that edited AZIN1 functions as an oncogene and a potential therapeutic target in CRC. Moreover, AZIN1 RNA editing status could be used as a clinically relevant prognostic indicator in CRC patients.

Rac GTPase activating protein (RacGAP) 1 plays a key role in controlling various cellular phenomena including cytokinesis, transformation, invasive migration, and metastasis. This study investigated the function and clinical significance of RacGAP1 expression in colorectal cancer (CRC). The intrinsic functions of RacGAP1 in CRC cells were analyzed using small interfering RNA (siRNA). We analyzed RacGAP1 mRNA expression in surgical specimens from 193 CRC patients (Cohort 1) by real-time polymerase chain reaction. Finally, we validated RacGAP1 protein expression using formalin-fixed paraffin-embedded samples from 298 CRC patients (Cohort 2) by immunohistochemistry. Reduced RacGAP1 expression by siRNA in CRC cell lines showed significantly decreased cellular proliferation, migration, and invasion. In Cohort 1, RacGAP1 expression in CRC was significantly higher than in adjacent normal mucosa, and increased according to TNM stage progression. High RacGAP1 expression in tumors was significantly associated with progression and prognosis. In Cohort 2, RacGAP1 protein was overexpressed mainly in the nuclei of CRC cells; however, its expression was scarcely observed in normal colorectal mucosa. RacGAP1 protein expression was significantly higher in CRC patients with higher T stage, vessel invasion, and lymph node and distant metastasis. Increased expression of RacGAP1 protein was significantly associated with poor disease-free and overall survival. Multivariate analyses revealed that high RacGAP1 expression was an independent predictive marker for lymph node metastasis, recurrence, and poor prognosis in CRC. Our data provide novel evidence for the biological and clinical significance of RacGAP1 as a potential biomarker for identifying patients with lymph node metastasis and poor prognosis in CRC.