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Abstract The role of thymidylate synthase (TS) is essential as a key rate-limiting enzyme in DNA synthesis. It is the primary target of fluorouracil and its derivates in colorectal cancer. In this study, TS mRNA expression was examined in primary tumor and normal tissues from 76 patients with high- risk stage II/III colorectal cancer by laser capture microdissection and polymerase chain reaction. Thirty (39.47%) patients were found to have higher TS expression in primary tumors with earlier stage (P = 0.018), lower histological grades (P = 0.001) and high frequency microsatellite instability (P = 0.000). Multivariate analysis showed that microsatellite instability, histological grade and number of lymph nodes examined are independent prognostic markers.

Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prognostic value of tumor deposits(TD)in N0 stage gastric cancer., Methods: A retrospective case-control study was performed on clinicopathological data of 751 N0 stage gastric cancer patients who underwent subsequent R0 gastrectomy from January 2011 to February 2013 at Zhengzhou University Affiliated Tumor Hospital. Patients were divided into TD-negative group (688 cases) and TD-positive group (63 cases). Propensity score matching was used to balance the covariances between the two groups, such as age, gender, differentiation degree, tumor location, T stage, perineural invasion, lymphovascular invasion, extent of resection, tumor size, surgical procedure,and chemotherapy. Matching was performed by the minimal adjacent method of 1:2 pairing. The survival analysis was carried out using Kaplan-Meier method,and differences between the curves were detected by log-rank test. Cox proportional hazard model was used to perform univariate analysis and multivariate analysis., Results: After matching,56 patients were allocated into the TD-positive group and 112 patients into the TD-negative group, and the baseline of clinicopathological data of 2 groups matched well (all P>0.05). The median follow-up time was 55.2 (12.0-83.2) months, and 3 patients were lost to follow-up (died of other diseases). In TD-positive group, 38 patients died of gastric cancer and 1 died of other disease. In TD-negative group, 52 patients died of gastric cancer and 2 died of other diseases. The TD-positive group had lower 5-year survival rate than TD-negative group (31.0% vs. 52.9%,χ²=6.230, P=0.014). Subgroup analysis showed that the 5-year survival rate of T1-2 stage TD-positive patients was significantly lower than that of T1-2 stage TD-negative patients (47.1% vs. 92.6%, χ²=11.433,P<0.001),while the difference between two groups with T3-4 stage (23.8% vs. 40.0%, χ²=2.995,P=0.084)was not significant. In patients receiving chemotherapy, the 5-year survival rate of TD-positive group was significantly lower than that of TD-negative group(34.1% vs. 54.8%, χ²=4.122, P=0.042). Further subgroup analysis showed that patients receiving postoperative chemotherapy of TD-positive group both in T1-2 stage (63.6% vs. 100%, χ²=3.830,P=0.048) and in T3-4 stage (24.2% vs. 48.4%, χ²=4.740,P=0.029) had significantly lower 5-year survival rates than those of TD-negative group. However,T1-2 stage TD-positive patients receiving chemotherapy had significantly higher 5-year survival rate as compared to those without receiving chemotherapy(63.6% vs. 16.7%, χ²=5.474,P=0.019).Univariate analysis revealed T stage (HR=1.829, 95%CI:1.490-2.245, P<0.001),perineural invasion (HR=2.620, 95%CI:1.617-4.246,P<0.001),tumor size (HR=1.646, 95%CI:1.078-2.512, P=0.021),TD(HR=1.691,95%CI:1.112-2.572,P=0.014) were associated with the prognosis of patients with gastric cancer. Multivariate analysis showed TD-positive (HR=2.035, 95%CI:1.325-3.126, P=0.001), later T stage (HR=1.812, 95%CI: 1.419-2.313,P<0.001), perineural invasion (HR=1.782,95%CI:1.058-3.002,P=0.030) were independent risk factors for the prognosis of gastric cancer., Conclusions: TD is an independent risk factor for N0 stage gastric cancer,and may be closely related to T stage. Patients with TD-positive stage T1-2 should receive chemotherapy, but the prognosis of TD-positive patients undergoing adjuvant chemotherapy is poorer as compared to TD-negative patients. Therefore, more individualized treatments should be administrated.

Objective: To compare the effects of neoadjuvant chemotherapy and adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer using propensity score matching method., Methods: Clinical data of patients with locally advanced gastric cancer undergoing open D2 radical gastrectomy between January 2012 and December 2014 at the Affiliated Tumor Hospital of Zhengzhou University were analyzed retrospectively. Sixty-five patients receiving neoadjuvant chemotherapy (NAC) were allocated into the NAC group and 1243 patients receiving postoperative adjuvant chemotherapy (AC) were allocated into the AC group., Inclusion Criteria: (1) age ranged from 18 to 75 years old, and biopsy specimen was confirmed as adenocarcinoma; (2) all the operative procedures were open D2 radical gastrectomy;(3)image examinations showed no distant metastasis or other unresectable factors., Exclusion Criteria: no open D2 radical gastrectomy, undergoing laparoscopic surgery, neoadjuvant chemotherapy course <2 cycles, without adjuvant chemotherapy, history of other malignancies, severe complications, incomplete data. SOX (tegafur-gimeracil-oteracil plus oxaliplatin) or XELOX (capecitabine plus oxaliplatin) was used as neoadjuvant and postoperative adjuvant chemotherapy regimen. One-to-two propensity score matching was performed to balance the covariance between two groups. Survival was analyzed using the Kaplan-Meier method. Differences between the curves were tested using log-rank test., Results: After balancing the covariates including gender, age, tumor location, degree of differentiation, clinical stage, chemotherapy regimen, chemotherapy course and surgical approach, 195 patients were enrolled, including 65 patients of the NAC group and 130 patients of the AC group. The number of harvested lymph nodes in NAC and AC group was 22.3±4.6 and 22.6±5.1 respectively, without statistically significant difference(t=1.125, P=0.263). Pathological response assessment for NAC group showed TRG0 in 6 cases, TRG1 in 8 cases, TRG2 in 17 cases, TRG3 in 34 cases; sensitive (TRG 0 to 2) in 31 cases (47.7%), non-sensitive in 34 cases (52.3%). The 3-year progression-free survival rate of NAC and AC group was 73.6%(95%CI: 62.8-84.3) and 69.9%(95%CI:62.1-77.7) respectively, which was not significantly different(P=0.361). The 3-year overall survival rate of NAC and AC group was 80.0%(95%CI:70.2-89.8) and 74.6%(95%CI:67.2-82.0) respectively, which was not significantly different as well(P=0.387). Subgroup analysis revealed that the 3-year progression-free survival rate and 3-year overall survival rate of sensitive patients in NAC group were 83.3%(95%CI:70.0-96.6) and 87.1%(95%CI:75.3-98.9) respectively, which were significantly higher than 62.4%(95%CI:46.1-78.7, P=0.037) and 70.2%(95%CI:54.7-85.7, P=0.033) of non-sensitive patients in NAC group, and those in AC group(P=0.044 and P=0.040)., Conclusions: Effects of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer are similar. Patients who are sensitive to neoadjuvant chemotherapy have better prognosis. It may be beneficial to improve prognosis that some appropriate patients with locally advanced gastric cancer are screened for neoadjuvant chemotherapy.

Objective: To evaluate the clinical features and prognosis of gastric cancer patients with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC)., Methods: Clinical data of 159 gastric cancer patients who received NAC followed by surgical resection between January 2012 and December 2014 at the Affiliated Tumor Hospital of Zhengzhou University were collected and clinical features of those with pCR were analyzed retrospectively. Kaplan-Meier method was used to estimate 3-year overall survival (OS) rate and recurrence-free survival (RFS) rate. Recurrence factors were analyzed by univariate and multivariate analysis with Cox proportional hazard model., Results: A total of 21 patients(13.2%) achieved pCR, including 13 male and 8 female cases, with the median age at diagnosis of 56 (40 to 70) years. Eleven cases were differentiated tumor and 10 were undifferentiated. Six cases were in clinical baseline stage II(, and 15 were in III(. Five cases received the mFOLFOX6 (oxaliplatin + leucovorin +5-FU), 6 received the SOX (oxaliplatin +S-1), 4 received the XELOX (oxaliplatin + capecitabine), 2 received the EOX (epirubicin + oxaliplatin +capecitabine) and 4 received the DOX (docetaxel + oxaliplatin +capecitabine) chemotherapy regimens. Two cases achieved CR, 18 achieved PR, and 1 was SD after NAC. The median (range) course of preoperative and postoperative chemotherapy were 4(2 to 5) and 2(0 to 5) . All the patients underwent R0 resection plus D2 lymphadenectomy, and 4 cases were performed with proximal gastrectomy, 3 cases were performed with distal gastrectomy, 13 cases were performed with total gastrectomy, and one case was performed with total gastrectomy plus pancreatic splenectomy. Pneumonia, abdominal bleeding and infection, anastomotic leakage, and gastroplegia occurred respectively in one case, who all were cured by conservative treatment. The median follow-up of the survivors was 39.3 (range 22.7 to 56.9) months. Three cases died of recurrence: 1 case in the liver, 1 in the lung, and 1 in the brain. Two cases developed recurrence and survived: 1 in the liver and 1 in celiac lymph nodes. The overall survival and 3-year recurrence-free survival rates were 90.2%(95%CI: 100 to 77.3) and 90.5%(95%CI: 100 to 78.0). Fourteen cases did not complete scheduled chemotherapy course, and the overall 3-year survival rate was 85.1%. Older age(>50 years old)(P=0.028, RR=0.063, 95%CI: 0.005 to 0.743) and no postoperative complication (P=0.023, RR=0.065, 95%CI: 0.006 to 0.689) were identified as independent prognostic factors with Cox multivariate analysis., Conclusion: Patients diagnosed as gastric cancer with pCR after NAC have good prognosis, but the pCR ratio is low, and those with younger age and more postoperative complications may have higher risk for recurrence and metastasis.