Wenquan Liang

Genome-Wide lncRNA Microarray Profiling Identifies Novel Circulating lncRNAs for Detection of Gastric Cancer.

Long non-coding RNAs (lncRNAs) can serve as blood-based biomarkers for cancer detection. To identify novel lncRNA biomarkers for gastric cancer (GC), we conducted, for the first time, genome-wide lncRNA screening analysis in two sets of samples: five paired preoperative and postoperative day 14 plasma samples from GC patients, and tissue samples from tumor and adjacent normal tissues. Candidate tumor-related lncRNAs were then quantitated and evaluated in three independent phases comprising 321 participants. The expression levels of lncRNAs were also measured in GC cell lines and the corresponding culture medium. Biomarker panels, lncRNA-based Index I and carcinoembryonic antigen (CEA)-based Index II, were constructed using logistic regression, and their diagnostic performance compared. Fagans nomogram was plotted to facilitate clinical application. As a result, we identified five novel plasma lncRNAs (TINCR, CCAT2, AOC4P, BANCR and LINC00857), which, when combined in the lncRNA-based Index I, outperformed the CEA-based Index II (P < 0.001) and could distinguish GC patients from healthy controls with an area under the receiver-operating curve (AUC) of 0.91 (95% confidence interval (CI): 0.88-0.95). The lncRNA-based index decreased significantly by postoperative day 14 (P = 0.016), indicating its ability to monitor tumor dynamics. High values of the lncRNA-based index were correlated with tumor size (P = 0.036), depth of invasion (P = 0.025), lymphatic metastasis (P = 0.012) and more advanced tumor stages (P = 0.003). The lncRNA-based index was also able to discriminate GC patients from precancerous individuals and patients with gastrointestinal stromal tumor with AUC values of 0.82 (95% CI: 0.71-0.92) and 0.80 (95% CI: 0.68-0.91), respectively. Taken together, our findings demonstrate that this panel of five plasma lncRNAs could serve as a set of novel diagnostic biomarkers for GC detection.

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

The prognosis of gastric cancer remains poor due to clinical drug resistance. Novel drugs are urgently needed. Shikonin (SHK), a natural naphthoquinone, has been reported to trigger cell death and overcome drug resistance in anti-tumour therapy. In this study, we investigated the effectiveness and molecular mechanisms of SHK in treatment with gastric cancer. In vitro, SHK suppresses proliferation and triggers cell death of gastric cancer cells but leads minor damage to gastric epithelial cells. SHK induces the generation of intracellular reactive oxygen species (ROS), depolarizes the mitochondrial membrane potential (MMP) and ultimately triggers mitochondria-mediated apoptosis. We confirmed that SHK induces apoptosis of gastric cancer cells not only in a caspase-dependent manner which releases Cytochrome C and triggers the caspase cascade, but also in a caspase-independent manner which mediates the nuclear translocation of apoptosis-inducing factor and Endonuclease G. Furthermore, we demonstrated that SHK enhanced the chemotherapeutic sensitivity of 5-fluorouracil and oxaliplatin in vitro and in vivo. Taken together, our data show that SHK may be a novel therapeutic agent in the clinical treatment of gastric cancer.

Timing of surgery after neoadjuvant chemotherapy for gastric cancer: Impact on outcomes

AIM To evaluate whether the neoadjuvant chemotherapy (NACT)-surgery interval time significantly impacts the pathological complete response (pCR) rate and long-term survival. METHODS One hundred and seventy-six patients with gastric cancer undergoing NACT and a planned gastrectomy at the Chinese PLA General Hospital were selected from January 2011 to January 2017. Univariate and multivariable analyses were used to investigate the impact of NACT-surgery interval time (< 4 wk, 4-6 wk, and > 6 wk) on pCR rate and overall survival (OS). RESULTS The NACT-surgery interval time and clinician T stage were independent predictors of pCR. The interval time > 6 wk was associated with a 74% higher odds of pCR as compared with an interval time of 4-6 wk (P = 0.044), while the odds ratio (OR) of clinical T3 vs clinical T4 stage for pCR was 2.90 (95%CI: 1.04-8.01, P = 0.041). In Cox regression analysis of long-term survival, post-neoadjuvant therapy pathological N (ypN) stage significantly impacted OS (N0 vs N3: HR = 0.16, 95%CI: 0.37-0.70, P = 0.015; N1 vs N3: HR = 0.14, 95%CI: 0.02-0.81, P = 0.029) and disease-free survival (DFS) (N0 vs N3: HR = 0.11, 95%CI: 0.24-0.52, P = 0.005; N1 vs N3: HR = 0.17, 95%CI: 0.02-0.71, P = 0.020). The surgical procedure also had a positive impact on OS and DFS. The hazard ratio of distal gastrectomy vs total gastrectomy was 0.12 (95%CI: 0.33-0.42, P = 0.001) for OS, and 0.13 (95%CI: 0.36-0.44, P = 0.001) for DFS. CONCLUSION The NACT-surgery interval time is associated with pCR but has no impact on survival, and an interval time > 6 wk has a relatively high odds of pCR.

Robot-Assisted Versus Laparoscopy-Assisted Proximal Gastrectomy for Early Gastric Cancer in the Upper Location: Comparison of Oncological Outcomes, Surgical Stress, and Nutritional Status

Background: An increasing amount of attention has been paid to minimally invasive function-preserving gastrectomy, with an increase in incidence of early gastric cancer in the upper stomach. This study aimed to compare oncological outcomes, surgical stress, and nutritional status between robot-assisted proximal gastrectomy (RAPG) and laparoscopy-assisted proximal gastrectomy (LAPG). Methods: Eighty-nine patients were enrolled in this retrospective study between November 2011 and December 2013. Among them, 27 patients underwent RAPG and 62 underwent LAPG. Perioperative parameters, surgical stress, nutritional status, disease-free survival, and overall survival were compared between the 2 groups. Results: Sex, age, and comorbidity were similar in the RAPG and LAPG groups. There were also similar perioperative outcomes regarding operation time, complications, and length of hospital stay between the groups. The reflux esophagitis rates following RAPG and LAPG were 18.5% and 14.5%, respectively (P = .842). However, patients in the RAPG group had less blood loss (P = .024), more harvested lymph nodes (P = .021), and higher costs than those in the LAPG group (P < .001). With regard to surgical stress, no significant differences were observed in C-reactive protein concentrations and white blood cell count on postoperative days 1, 3, and 7 between the groups (Ps > .05). There appeared to be higher hemoglobin levels at 6 months (P = .053) and a higher body mass index at 12 months (P = .056) postoperatively in patients in the RAPG group compared with those in the LAPG group, but this difference was not significant. Similar disease-free survival and overall survival rates were observed between the groups. Conclusions: RAPG could be an alternative to LAPG for patients with early gastric cancer in the upper stomach with comparable oncological safety and nutritional status. Further well-designed, prospective, large-scale studies are needed to validate these results.

Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer

Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon, has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer. We found that shikonin suppressed the growth of colon cancer cells in a dose-dependent manner in vitro and in vivo. Shikonin induced mitochondria-mediated apoptosis, which was regulated by Bcl-2 family proteins. Shikonin increased the generation of intracellular ROS, which played an upstream role in shikonin-induced apoptosis. Our data indicated that generation of ROS, down-regulated expression of Bcl-2 and Bcl-xL, depolarization of the mitochondrial membrane potential and activation of the caspase cascade were components of the programmed event of shikonin-induced apoptosis in colon cancer cells. In addition, shikonin presented minimal toxicity to non-neoplastic colon cells and no liver injury in xenograft models, showing safety in the control of colon cancer cell growth in vitro and in vivo. Taken together, our findings suggest that shikonin might serve as a potential novel therapeutic drug in the treatment of human colon cancer.

Evaluation of hepatectomy and palliative local treatments for gastric cancer patients with liver metastases: a propensity score matching analysis

Background The optimal treatments for gastric cancer with liver metastases (GCLM) remain controversial. This study aimed to evaluate the efficacy of hepatectomy, RFA and TACE as local treatments for GCLM. Methods From 2001 to 2015, 119 consecutive patients who received multidisciplinary treatments based on curative gastrectomy and local treatments (hepatectomy, RFA and TACE) for liver metastases were enrolled in this retrospective cohort study. Patients were divided into Group A (46, hepatectomy) and Group B (73, either or both RFA and TACE). Propensity score matching analysis was employed. Results The propensity model revealed that hepatectomy was associated with significantly longer OS compared with either or both RFA and TACE (P=0.021). The 1-, 3- and 5-year OS rates were 80.5%, 41.5% and 24.4%, respectively in Group A; and 85.4%, 21.9% and 12.2%, respectively in Group B. Subgroup analyses indicated that hepatectomy was associated with significantly longer long-term survival compared with TACE (P=0.033) and RFA (P=0.010). TACE had a similar efficacy as RFA (P=0.518), but with significantly lower costs (P=0.014) in for patients with metachronous GCLM. Conclusion Hepatectomy is the optimal local treatment for GCLM when surgical R0 resection is intended. TACE attained a similar prognosis as RFA with relatively high cost-effectiveness, particularly for patients with metachronous GCLM.BACKGROUND The optimal treatments for gastric cancer with liver metastases (GCLM) remain controversial. This study aimed to evaluate the efficacy of hepatectomy, RFA and TACE as local treatments for GCLM. METHODS From 2001 to 2015, 119 consecutive patients who received multidisciplinary treatments based on curative gastrectomy and local treatments (hepatectomy, RFA and TACE) for liver metastases were enrolled in this retrospective cohort study. Patients were divided into Group A (46, hepatectomy) and Group B (73, either or both RFA and TACE). Propensity score matching analysis was employed. RESULTS The propensity model revealed that hepatectomy was associated with significantly longer OS compared with either or both RFA and TACE (P=0.021). The 1-, 3- and 5-year OS rates were 80.5%, 41.5% and 24.4%, respectively in Group A; and 85.4%, 21.9% and 12.2%, respectively in Group B. Subgroup analyses indicated that hepatectomy was associated with significantly longer long-term survival compared with TACE (P=0.033) and RFA (P=0.010). TACE had a similar efficacy as RFA (P=0.518), but with significantly lower costs (P=0.014) in for patients with metachronous GCLM. CONCLUSION Hepatectomy is the optimal local treatment for GCLM when surgical R0 resection is intended. TACE attained a similar prognosis as RFA with relatively high cost-effectiveness, particularly for patients with metachronous GCLM.