Zerong Cai

Significance of mTOR Signaling and Its Inhibitor Against Cancer Stem-Like Cells in Colorectal Cancer

PurposeTo determine the role of the mammalian target of rapamycin (mTOR) signaling in sustaining cancer stem-like cells and its clinical values in colorectal cancer (CRC).MethodsmTOR expression in CRC patients was analyzed by immunohistochemistry and survival analysis was used to confirm the clinical value of mTOR. Colorectal cell lines were treated by mTOR inhibitors rapamycin and PP242, and sphere formation assay and aldehyde dehydrogenase (ALDH) assay were utilized to determine the impact of mTOR inhibition in CRC stem-like cells, combined or not combined with chemotherapeutic drug (fluorouracil and oxaliplatin).ResultsmTOR expression was associated with outcomes of CRC patients and predicted poor prognosis in stage II CRC patients. mTOR signaling was activated in stem-like colorectal cancer cells, and mTOR inhibitors (rapamycin and PP242) decreased the capacity of sphere formation as well as ALDH activity. Furthermore, mTOR inhibitors also were demonstrated to suppress the stimulation of stem-like cells by chemotherapy.ConclusionsmTOR shared predictive significance in stage II CRC patients’ outcomes and played a vital role in the maintenance of colorectal cancer stem-like cells. mTOR inhibitors might hold the potential to become a therapeutic target against CRC stem cells.

CCL21 as an independent favorable prognostic factor for stage III/IV colorectal cancer

The aim of the present study was to investigate the expression dynamics of CCL21 and its prognostic significance in human stage III/IV colorectal cancer (CRC). CCL21 expression dynamics were detected with western blotting. The expression of CCL21 in CRC tissue microarrays was examined by immunohistochemistry. The optimal cut-point of CCL21 expression was assessed by the X-tile program. The prognostic significance was analyzed using both Kaplan-Meier curves and Cox regression analysis. Western blot analysis demonstrated that CCL21 expression was comparable in the CRC and normal colorectal tissues. According to the X-tile program, the cut-point for high expression of CCL21 in CRC was determined when the CCL21 expression index was >56.1. Overexpression of CCL21 was significantly correlated with larger tumor diameter, more mucinous carcinoma or signet ring cell carcinoma and poor tumor differentiation. Patients with high expression of CCL21 had a higher overall survival rate in comparison to patients with low expression. In the multivariate Cox regression analysis, CCL21 expression was found to be an independent prognostic biomarker for CRC. ROC curves showed that CCL21 expression could improve the prognostic capability of TNM stage in stage III/IV CRC patients. High expression of CCL21 is an independent and useful biomarker for predicting longer survival of stage III/IV CRC patients.

Tumor Volume Reduction Rate Predicts Pathologic Tumor Response of Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemotherapy alone: Results from a Prospective Trial.

Purpose: To evaluate tumor volume reduction rate (TVRR) measured by three-dimensional region-of-interest (3D-ROI) magnetic resonance (MR) volumetry in predicting pathological tumor response of preoperative chemotherapy alone for locally advanced rectal cancer (LARC). Methods: LARC patients who received neoadjuvant chemotherapy only from a prospective and randomized trial were recruited. Tumor volumes were measured with 3D-ROI MR volumetry. TVRR was determined using the equation TVRR = (VPre-Therapy - VPost-Therapy) / VPre-Therapy ×100%. Correlation between TVRR and clinical or pathological characteristics and predictive value of TVRR for pathological tumor response in terms of Tumor Regression Grade (TRG), T downstage, N downstage and overall downstage were analyzed. Results: 80 eligible cases of LARC were included in our study with TVRR of (51.7±25.1) %. TVRR was higher in well-differentiated tumors compared with poor-differentiated tumors (P=0.040). TVRR was found to be related with TRG (P<0.001), T downstage (P<0.001) and overall downstage (P<0.001). Risk of achieving TRG 2/3 decreased to 57.5% (P=0.002) and odds of achieving overall downstage increase to 179.3% (P<0.001) when TVRR increased by every 10%. A sensitivity of 0.704 and specificity of 0.804 were calculated when ROC curve was constructed to predict TRG using TVRR with a cutoff of 65%. Conclusion: TVRR is correlated with TRG and overall downstage significantly in LARC patients treated with preoperative chemotherapy alone and shows great value in predicting favorable TRG and overall downstage with good sensitivity and specificity. It could be considered as a promising parameter candidate for efficacy evaluation.

MicroRNA 26b promotes colorectal cancer metastasis by downregulating phosphatase and tensin homolog and wingless-type MMTV integration site family member 5A

Invasion and metastasis are crucially important factors in the survival of malignant tumors. Epithelial‐mesenchymal transition (EMT) is an early step in metastatic progression and the presence of cancer stem cells is closely related to tumor survival, proliferation, metastasis, and recurrence. Herein we report that ectopic overexpression of microRNA 26b (miR‐26b) in colorectal cancer (CRC) cell lines promoted EMT and stem cell‐like phenotypes in vitro. Furthermore, miR‐26b directly targeted and suppressed multiple tumor suppressors, including phosphatase and tensin homolog (PTEN) and wingless‐type MMTV integration site family member 5A (WNT5A). Notably, miR‐26b is markedly upregulated in tumor samples from patients with lymphatic metastases. These results indicate that miR‐26b promotes CRC metastasis by downregulating PTEN and WNT5A, and may represent a therapeutic target for metastatic CRC.

Accessing new prognostic significance of preoperative carcinoembryonic antigen in colorectal cancer receiving tumor resection: More than positive and negative.

OBJECTIVE Evaluating the prognostic significance of carcinoembryonic antigen (CEA) for colorectal cancer (CRC) patients in new cutoffs. PATIENTS Three hundred and seventy cases and 1164 cases of CRC patients receiving tumor resection from hospitals of Sun Yat-sen University were retrospectively investigated as training cohort and validation cohort respectively. CEA was categorized into quintiles for Kaplan-Meier analysis and Cox proportional hazards regression analysis. RESULTS CEA was categorized into quintiles with the cutoff points of (0-1.5) ng/ml, (1.5-2.3) ng/ml, (2.3-3.98) ng/ml, (3.98-8.02) ng/ml, (8.02-Maximum) ng/ml. In CRC patients from training cohort, progressively worse outcomes were observed in each increasing quintile of CEA in term of overall survival (Log-rank Test: P< 0.0001, Log-rank Test for Trend: P< 0.0001) and progression free survival (Log-rank Test: P= 0.0002, Log-rank Test for Trend: P< 0.0001). CEA quintile was associated with overall survival (HR: 1.209, 95%CI: 1.033-1.416, P= 0.018) and progression free survival (HR: 1.195, 95%CI: 1.024-1.394, P= 0.024). Validation analysis also showed that patients with increasing CEA quintile suffered unfavorable overall survival (Log-rank Test: P= 0.0001, Log-rank Test for Trend: P= 0.0001) and progression free survival (Log-rank Test: P= 0.0001, Log-rank Test for Trend: P= 0.0001). CEA quintile was associated with overall survival (HR: 1.330, 95%CI: 1.123-1.576, P< 0.001) and progression free survival (HR: 1.218, 95%CI: 1.089-1.362, P= 0.001). CONCLUSIONS Preoperative CEA quintile was an independent predictor of unfavorable prognosis in CRC patients. Even within normal range, CEA quintile might still impact prognosis outcomes of CRC.

Letter to the editor: one point cancer of ileal adenocarcinoma complicated from Crohn’s disease

To the Editor, Crohn’s disease is common in Western countries, and its morbidity increased rapidly in the past decades in Eastern races. Small bowel adenocarcinoma is a relatively rare complication in Crohn’s disease and often accompanied by symptoms of obstruction, fistula or metastasis [1]. In China, small bowel adenocarcinoma is rarely seen in Crohn’s disease cases. Here, we describe a case of ileal adenocarcinoma complicated from Crohn’s disease in orient patient, presented by “one point cancer.”