Laparoscopic surgery is an acceptable alternative to open surgery in colorectal cancer treatment. However, in gastric cancer, there is not much scientific evidence. Here, we proposed a prospective randomized clinical trial to evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. From October 2010 to September 2012, 300 patients with gastric cancer were randomized to undergo either laparoscopy-assisted gastrectomy (LAG) or conventional open gastrectomy (OG) with D2 dissection. Clinicopathological parameters, recovery and complications were compared between these two groups. Thirty cases were excluded because of refusing to be involved in the trial, having peritoneal seeding metastasis or LAG conversed to OG, and finally 270 cases were analyzed (128 in LAG and 142 in OG). No significant differences were observed in gender, age, body mass index, stages and types of radical resection [radical proximal gastrectomy (PG + D2), radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)] (P > 0.05). The number of harvested lymph nodes (HLNs) was similar (29.3 ± 11.8 in LAG vs. 30.1 ± 11.4 in OG, P = 0.574). And in the same type of radical resection, no significant difference was found in the number of HLNs between the two groups (PG + D2, P = 0.770; DG + D2, P = 0.500; TG + D2, P = 0.993). The morbidity of the LAG group (21.8 %) was also comparable to the OG group (19.0 %, P = 0.560). However, the LAG group had significantly less blood loss and faster recovery, and a longer operation time (P < 0.05). Laparoscopic D2 dissection is feasible, safe and capable of fulfilling oncologic criteria for the treatment of gastric cancer.

BackgroundSerine/threonine protein kinase 25 (STK25) is critical in regulating whole-body glucose and insulin homeostasis and the accumulation of ectopic lipids. The Warburg effect, also known as aerobic glycolysis, is an essential metabolic characteristic of cancer cells. However, the effects of STK25 on aerobic glycolysis of cancer cells remain unexplored. The aim of this study is to investigate the role of STK25 in colorectal cancer (CRC) and to elucidate the underlying mechanisms.MethodsThe influences of STK25 on the cell proliferation were evaluated by MTT and colony formation assays. The roles of STK25 in aerobic glycolysis were determined by glucose uptake and lactate production assays. The interaction between STK25 and GOLPH3 was detected by co-immunoprecipitation, GST pull-down, and His-tag pull-down assays. Western blot was used to measure the expression of glycolytic genes, and the status of kinases in mTOR pathway. Moreover, a xenograft mouse model was used to investigate the effects of STK25 in vivo. The prognostic significance of STK25 was analyzed using public CRC datasets by a log-rank test.ResultsSTK25 suppressed proliferation, glycolysis and glycolytic gene expression in CRC cells. STK25 interacted with GOLPH3 and mediated glycolysis through GOLPH3-regulated mTOR signaling. Consistent with these observations, silencing of STK25 promoted tumor growth and glycolytic gene expression in an in vivo xenograft mouse model. Moreover, high levels of STK25 correlated with favorable prognosis in patients with CRC.ConclusionsOur results demonstrated that STK25 negatively regulates the proliferation and glycolysis via GOLPH3-dependent mTOR signaling. Accordingly, STK25 could be a potential therapeutic target for the treatment of CRC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0808-1) contains supplementary material, which is available to authorized users.

As a mitotic kinesin, kinesin family member 14 (KIF14) has been reported to serve oncogenic roles in a variety of malignancies; however, its functional role and regulatory mechanisms in colorectal cancer (CRC) remain unclear. In the present study, KIF14 was observed to be markedly overexpressed in CRC, and this upregulation was associated with tumor size and marker of proliferation Ki-67 immunostaining scores. Gain- and loss-of-function experiments were applied to identify the function of KIF14 in CRC progression. In vitro and in vivo assays revealed that KIF14 promoted CRC cell proliferation and accelerated the cell cycle via activation of protein kinase B. In addition, the present study investigated the potential mechanisms underlying KIF14 overexpression in CRC. Bioinformatics analyses and validation experiments, including reverse transcription-quantitative polymerase chain reaction, western blotting and a Dual-Luciferase reporter assay, demonstrated that, in addition to genomic amplification and transcriptional activation, KIF14 was regulated by microRNA (miR)-200c at the post-transcriptional level. Rescue experiments further demonstrated that decreased miR-200c expression could facilitate KIF14 to exert its pro-proliferative role. The expression of miR-200c was negatively correlated with KIF14 in CRC specimens. Collectively, the findings of the present study demonstrated the oncogenic role of KIF14 in colorectal tumorigenesis, and also revealed a complexity of regulatory mechanisms mediating KIF14 overexpression, which may provide insight for developing novel treatments for patients with CRC.

The expression of stem cell genes was detected in a small proportion of tumor cells present in ascites as well as in tumor tissue. IL-6 plays an important role in the induction of c-Myc.

Sporadic synchronous colorectal cancer (CRC) refers to more than one primary tumor detected in a single patient at the time of the first diagnosis without predisposition of cancer development. Given the same genetic and microenvironment they raise, sporadic synchronous CRC is a unique model to study CRC tumorigenesis. We performed whole exome sequencing in 32 fresh frozen tumor lesions from 15 patients with sporadic synchronous CRC to compare their genetic alterations. This approach identified ubiquitously mutated genes in the range from 0.34% to 4.22% and from 0.8% to 7.0% in non-hypermutated tumors and hypermutated tumors, respectively, in a single patient. We show that both ubiquitously mutated genes and candidate cancer genes from different tumors in the same patient mutated at different sites. Consistently, obvious differences in somatic copy number variations (SCNV) were found in most patients with non-hypermutated tumor lesions, which had ubiquitous copy number amplification rates ranging from 0% to 8.8% and ubiquitous copy number deletion rates ranging from 0% to 8.2%. Hypermutated lesions were nearly diploid with 0% to 18.8% common copy number aberrations. Accordingly, clonal structures, altered signaling pathways and druggable genes in a single patient with synchronous CRC varied significantly. Taken together, the disparate SCNVs and mutations in synchronous CRC supported the field effect theory of tumorigenesis. Moreover, the intertumor heterogeneity of synchronous CRCs implies that analysis of all tumor lesions from the same patient is necessary for appropriate clinical treatment decisions.

BackgroundGolgi phosphoprotein 3 (GOLPH3) has been validated as a potent oncogene involved in the progression of many types of solid tumors, and its overexpression is associated with poor clinical outcome in many cancers. However, it is still unknown the association of GOLPH3 expression with the prognosis of colorectal cancer (CRC) patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy.MethodsThe expression of GOLPH3 was determined by qRT-PCR and immunohistochemistry in colorectal tissues from CRC patients treated with 5-FU based adjuvant chemotherapy after surgery. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. The effects of GOLPH3 on 5-FU sensitivity were examined in CRC cell lines.ResultsGOLPH3 expression was elevated in CRC tissues compared with matched adjacent noncancerous tissues. Kaplan-Meier survival curves indicated that high GOLPH3 expression was significantly associated with prolonged disease-free survival (DFS, P = 0.002) and overall survival (OS, P = 0.011) in patients who received 5-FU-based adjuvant chemotherapy. Moreover, multivariate analysis showed that GOLPH3 expression was an independent prognostic factor for DFS in CRC patients treated with 5-FU-based chemotherapy (HR, 0.468; 95%CI, 0.222-0.987; P = 0.046). In vitro, overexpression of GOLPH3 facilitated the 5-FU chemosensitivity in CRC cells; while siRNA-mediated knockdown of GOLPH3 reduced the sensitivity of CRC cells to 5-FU-induced apoptosis.ConclusionsOur results suggest that GOLPH3 is associated with prognosis in CRC patients treated with postoperative 5-FU-based adjuvant chemotherapy, and may serve as a potential indicator to predict 5-FU chemosensitivity.

The MSKCC nomogram for colon cancer provides more accurate survival predictions than the AJCC staging system when applied to an external Chinese cohort. The MSKCC nomogram improved individualized prediction of survival and may aid in more accurate patient counseling, selection of various treatment options, and follow-up scheduling.

BackgroundColorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors.MethodsWe sequenced nine tumor regions and 88 single cells from two rectal cancer patients with tumors of the same molecular classification and characterized their mutation profiles and somatic copy number alterations (SCNAs) at the multi-region and the single-cell levels.ResultsA variable extent of genomic heterogeneity was observed between the two patients, and the degree of ITH increased when analyzed on the single-cell level. We found that major SCNAs were early events in cancer development and inherited steadily. Single-cell sequencing revealed mutations and SCNAs which were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer at regional and single-cell resolution and demonstrated that variable heterogeneity existed in two patients. The mutational scenarios and SCNA profiles of two patients with treatment naïve from the same molecular subtype are quite different.ConclusionsOur results suggest each tumor possesses its own architecture, which may result in different diagnosis, prognosis, and drug responses. Remarkable ITH exists in the two patients we have studied, providing a preliminary impression of ITH in rectal cancer.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3777-4) contains supplementary material, which is available to authorized users.