Zhixiang Jian

MiR-144 suppresses cell proliferation, migration, and invasion in hepatocellular carcinoma by targeting SMAD4.

Background/aim Increasing evidence show microRNAs (miRNAs) are engaged in hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of miR-144 in HCC, as well as to identify its underlying mechanism. Methods The expression levels of miR-144 were assessed in multiple HCC cell lines, as well as in liver tissues from patients with HCC. We further examined the effects of miR-144 on HCC. The molecular target of miR-144 was identified using a computer algorithm and confirmed experimentally. Results We found that the levels of miR-144 were frequently downregulated in human HCC tissues and cell lines, and overexpression of miR-144 dramatically inhibited HCC metastasis, invasion, cell cycle, epithelial–mesenchymal transition, and chemoresistance. We further verified the SMAD4 as a novel and direct target of miR-144 in HCCs. Conclusion Taken together, overexpression of miR-144 or downregulation of SMAD4 may prove beneficial as therapeutic strategies for HCC treatment.

The prognostic value of GLUT1 in cancers: a systematic review and meta-analysis.

Increased glycolysis is one of the hallmarks of cancer. The abnormal expression of glucose transporter 1 (GLUT1) was reported to be associated with resistance to current therapy and poor prognosis. Numerous studies have investigated the correlation between GLUT1 expression and prognosis in cancers, but the conclusions are still controversial. Here, we conducted a meta-analysis to explore the association between GLUT1 and survival in human cancers. PubMed, Springer, Medline, and Cochrane Library were searched carefully to identify eligible studies evaluating prognostic value of GLUT1 in cancers. Twenty-seven studies with 4079 patients were included in the present study. Our pooled results identified that increased expression of GLUT1 was associated with unfavorable overall survival (HR = 1.780, 95% CI = 1.574–.013, p < 0.001)) and poorer disease-free survival (HR = 1.95, 95% CI = 1.229–3.095, p = 0.003). Furthermore, overexpression of GLUT1 linked with poor differentiated tumors (RR = 1.380, 95% CI = 1.086–1.755, p = 0.009; I2 = 72.0%, p < 0.001), positive lymph node metastasis (RR = 1.395, 95% CI = 1.082–1.799, p = 0.010; I2 = 70.8%, p = 0.002) and larger tumor size (RR = 1.405, 95% CI = 1.231–1.603, p < 0.001; I2 = 37.3%, p = 0.093). This systematic review and meta-analysis indicated that the GLUT1 may serve as an ideal prognostic biomarker in various cancers.

Too Much Water Drowned the Miller-Does Extended Pancreaticoduodenectomy Benefit the Long-term Survival Outcomes in the Treatment of Pancreatic Cancer?

To the Editor:We read with interest the article by Jang et al1 prospectively evaluating the survival benefit of dissection of the nerve plexus and lymphadenectomy in patients with pancreatic head cancer. In that randomized controlled trial (RCT), they concluded that compared with extended pancreatic

Pretreatment hematologic markers as prognostic predictors of gastroenteropancreatic neuroendocrine tumors: a systematic review and meta-analysis

Background Systemic inflammation can be reflected by peripheral hematologic parameters and combined index like the lymphocyte count, neutrophil count, platelet count, neutrophil-to-lymphocyte (NLR), and platelet-to-lymphocyte ratio (PLR). This systematic review and meta-analysis aimed to summarize the association between the hematologic markers and prognosis of gastroenteropancreatic neuroendocrine tumors (GEP–NETs). Methods A computerized systematic search of PubMed, Embase, and Web of Science was conducted up to August 2016. Studies evaluating prognosis value of hematologic parameters in patients with GEP–NETs were retrieved. For meta-analysis, hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and synthesized using Review Manager software. Results We identified eight retrospective cohort studies comprising a total of 724 cases. The majority of included studies focused on pancreatic neuroendocrine tumors (PNETs). The prognostic values of NLR, PLR, and platelet count were reported in six studies, two studies, and one study, respectively. All the parameters were associated with prognostic outcomes in patients with GEP–NETs. A high NLR was significantly associated with poor prognosis in GEP–NETs (pooled HR 3.05, 95% CI 1.96–4.76, I2 = 0%, P < 0.00001 for overall survival (OS); pooled HR 3.30, 95% CI 2.04–5.32, I2 = 0%, P < 0.00001 for recurrence-free survival [RFS]). In PNETs, pooled-analyses also showed significant superiority of a low NLR on OS (pooled HR 4.21, 95% CI 1.95–9.13, I2 = 0%, P = 0.0003) and RFS (pooled HR 5.37, 95% CI 2.14–13.47, I2 = 0%, P = 0.003). Conclusions These findings suggest that the elevated NLR could be an adverse prognosis factor for GEP–NETs. The conclusion should be mainly limited to PNETs as the majority of included cases were PNET patients. The prognostic value of other hematologic parameters deserves further investigation. We recommend that further studies should use a continuous NLR variable and adopt a prospective and matched study design.

Decreased expression of LKB1 predicts poor prognosis in pancreatic neuroendocrine tumor patients undergoing curative resection

Background Liver kinase B1 (LKB1) is a key regulatory protein of cellular metabolism, proliferation, and polarity. The present study aimed to characterize the expression pattern of LKB1 in pancreatic neuroendocrine tumors (pNETs) and evaluate the relationship between LKB1 expression and prognosis in pNETs. Patients and methods We retrospectively analyzed the pathologic and clinical data of 71 pNET patients who underwent curative surgical resection in Guangdong General Hospital. LKB1 mRNA and protein levels in tumor tissues and paired nontumor tissues were evaluated in 24 patients by quantitative real-time reverse-transcription polymerase chain reaction and Western blot, respectively. Immunohistochemical expression of LKB1 in tumor tissues was detected in all of the 71 patients, and the immunohistochemical expression level was re-coded in two classes (high versus low/negative) and correlated with clinicopathological parameters and survival outcomes. The association between LKB1 expression and clinicopathological characters was evaluated by chi-square test and Student’s t-test. Kaplan–Meier curves and log-rank test were used to analyze the survival outcomes, including overall survival (OS) and disease-free survival (DFS). Results Compared to adjacent normal tissues, LKB1 mRNA level and protein expression level in tumor tissues were both increased. The immunostaining of LKB1 was mainly found within the cytoplasm. Overall, 52 of 71 (73.2%) cases were positive for LKB1 protein, which showed either a diffuse staining pattern or a partial staining pattern. Decreased LKB1 expression was correlated with older age (P=0.042), increased Ki-67 index (P=0.004), increased mitotic count (P=0.001), and advanced histologic grade (P=0.001). Moreover, patients with low/negative LKB1 expression had shorter OS and DFS than those with high expression. Conclusion Our results suggested that LKB1 expression could be a useful prognostic marker for recurrence and survival in pNET patients who had received curative resection.

Revision of Surgical Margin under Frozen Section to Achieve R0 Status on Survival in Patients with Pancreatic Cancer

ObjectiveThe aim is to investigate whether additional resection based on intraoperative frozen section (FS) to a secondary R0(s) status are associated with different long-term survivals in pancreatic cancer patients, comparing to those with R1 or primary R0(p) status.MethodsA systematic literature search (PubMed, Embase, Science Citation Index, Springer-Link, and Cochrane Central Register of Controlled Trials) was performed to identify all studies published up to June 2017. Survivals of patients undergoing pancreatic surgery according to the results of FS and re-resection were pooled for analysis.ResultsFive cohort studies were qualified for inclusion in this review with a total of 2980 patients. Long-term survival outcomes favored R0(p) resection as compared to R0(s) resection (HR = 1.58, 95%CI 1.24–2.01, P = 0.0002, I2 = 58%). No significant difference was observed for patients with or without additional resection at the time of surgery when positive FS was detected (HR = 0.98, 95CI% 0.65–1.47, P = 0.91, I2 = 81%).ConclusionsThe present study did not support the concept of achieving an R0 resection by intraoperative re-resection would benefit the patient’s survival. R1 margin at the time of surgery is more like a marker of aggressive tumor biology. Future well-designed randomized controlled trials are needed to confirm the conclusion.

IL-6/STAT3 pathway intermediates M1/M2 macrophage polarization during the development of hepatocellular carcinoma: YIN et al.

Human cancers, including hepatocellular carcinoma (HCC), are characterized by a high degree of drug resistance in chemotherapy. However, the underlying molecular mechanism remains unknown. To the role of interleukin‐6 (IL‐6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in the regulation of macrophage polarization, M1‐type and M2‐type macrophages were separately induced using lipopolysaccharide and interleukin‐4 (IL‐4), and we found that the IL‐6/STAT3 signaling pathway was inhibited in M1‐type macrophages but activated in M2‐type macrophages. After anti‐IL‐6‐treated macrophages were separately induced by lipopolysaccharide and IL‐4, we found that the inhibition of IL‐6/STAT3 signaling pathway turned macrophages into M1‐type. Co‐culture with M1‐type macrophages reduced HCC cell viability, proliferation, invasion, migration, drug resistance, but increased apoptosis. Co‐culture with M2‐type macrophages yielded reciprocal results. The inhibition of IL‐6/STAT3 signaling pathway mediated by anti‐IL6 was shown to significantly enhance the effects of M1‐type macrophages on HCC cells and rescue HCC cells from co‐culture with M2‐type macrophages. Tumor xenografts of co‐cultured HCC cells were established in nude mice and the results showed that the inhibition of IL‐6/STAT3 signaling pathway mediated by anti‐IL6 was found to reduce tumor formation of HCC cells co‐cultured with M1‐ or M2‐type macrophages and lung metastases. The current study reveals a novel mechanism of IL‐6/STAT3 signaling pathway in the regulation of macrophage polarization, thus contributing to HCC metastasis and drug resistance in chemotherapy.

A meta-analysis of long-term survival outcomes between surgical resection and radiofrequency ablation in patients with single hepatocellular carcinoma ≤ 2 cm (BCLC very early stage)

INTRODUCTION The optimal management choice in consideration of long-term overall survival (OS) and disease-free survival (DFS) for patients with BLCL very early stage is a matter of debate. AIM A systematic review and meta-analysis was conducted to evaluate the efficacy of liver resection (RES) and radiofrequency ablation (RFA) for single HCC 2 cm or less. MATERIAL AND METHOD The primary sources of the reviewed studies through December 2017, without restriction on the languages or regions, were Pubmed and Embase. The hazard ratio (HR) was used as a summary statistic for long-term outcomes. RESULTS A total of 5 studies qualified for inclusion in this quantified meta-analysis with a total of 729 HCC patients of BCLC very early stage. Only postoperative 1-year OS was comparable in both RES and RFA groups. As for long-term outcomes of 3-year and 5-year OSs, RES was significantly better than RFA, the HRs were 0.64 (95%CI: 0.41, 1.00; P = 0.05) and 0.63 (95%CI: 0.42, 0.95; P = 0.03) respectively. In terms of postoperative DFS, reduced tumor recurrence was observed in RES, and all the short- and long-terms outcomes were favored RES. DISCUSSION RES offers better long-term oncologic outcomes compared with RFA in current clinical evidences.

Safety and Feasibility of a Laparoscopy-Assisted Non-Anatomic Resection Technique for Hepatocellular Carcinoma Located at Right Posterior Segments in Cirrhotic Patients: A Case-Controlled Study with Propensity Score Matching

Purpose: The aim of this study was to compare the short- and long-term outcomes of laparoscopy-assisted resection for right posterior segment (LAR-RPS) with open resection (OR-RPS) performed by experienced hepatobiliary surgeons. Methods: This was a prospective comparative nonrandomized study. Results: The groups were comparable in terms of baseline demographics and clinicopathological data. Reduced operative time (254.88 ± 78.56 vs. 347.95 ± 82.56 min; p = 0.04) and estimated blood loss (477 ± 756 vs. 712 ± 836 mL; p = 0.03) were observed in LAR-RPS. Also, significant less duration of hospital stay (7.53 ± 2.68 vs. 12.57 ± 3.21 days; p < 0.001) was associated with LAR-RPS compared to OR-RPS. Long-term oncologic outcomes were comparable in 2 groups, in terms of both the overall and disease-free survival rates (p = 0.450 and 0.463, respectively). Conclusions: This study confirms that laparoscopic-assisted resection is a safe and effective operative procedure in those cirrhotic patients with a lesion in the right posterior section of the liver. When compared to the open approach, the laparoscopic-assisted approach reduces operative time and blood loss, as well as the length of hospital stay.