Prognostic value of systemic immune.inflammation index in patients with gastric cancer

Background:Inflammation-based indexes have been used to predict survival and recurrence in cancer patients.Systemic immune-inflammation index(Sll) was reported to be associated with prognosis in some malignant tumors.In the present study,we aimed to explore the association between Sll and the prognosis of patients with gastric cancer.Methods:We retrospectively analyzed data from 444 gastric cancer patients who underwent gastrectomy at the First Affiliated Hospital of Sun Yat-sen University between January 1994 and December 2005.Preoperative Sll was calculated.The Chi square test or Fisher's exact test was used to determine the relationship between preoperative Sll and clinicopathologic characteristics.Overall survival(OS) rates were estimated using the Kaplan-Meier method,and the effect of Sll on OS was analyzed using the Cox proportional hazards model.Receiver operating characteristic(ROC)curves were used to compare the predictive ability of Sll,NLR,and PLR.Results:Sll equal to or higher than 660 was significantly associated with old age,large tumor size,unfavorable Borrmann classification,advanced tumor invasion,lymph node metastasis,distant metastasis,advanced TNM stage,and high carcino-embryonic antigen level,high neutrophil-lymphocyte ratio,and high platelet-lymphocyte ratio(all P<0.05).High Sll was significantly associated with unfavorable prognosis(P<0.001) and Sll was an independent predictor for OS(P=0.015).Subgroups analysis further showed significant associations between high Sll and short OS in stage Ⅰ,Ⅱ,Ⅲ subgroups(all P<0.05).Sll was superior to NLR and PLR for predicting OS in patients with gastric cancer.Conclusion:Preoperative Sll level is an independent prognostic factor for OS in patients with gastric cancer.

MicroRNA-188-5p targeting Forkhead Box L1 promotes colorectal cancer progression via activating Wnt/β-catenin signaling

Objective:MicroRNA-188-5p(miR-188)enhances oncologic progression in various human malignancies.This study aimed to explore its role in colorectal cancer(CRC).Materials and Methods:Human CRC tissues paired with normal tissues,and several CRC cell lines were utilized.Real-time quantitative PCR was applied to measure the expression of miR-188.Overexpression and knockdown were used to access the function of miR-188 and to investigate whether FOXL1/Wnt signaling mediates such function.The proliferation,migration and invasion of cancer cells were evaluated by CCK8,wound-healing and transwell assays,respectively.Whether FOXL1 acted as a direct target of miR-188 was verified by dual-luciferase reporter assays.Results:Levels of miR-188 were upregulated in CRC tissues than in paired-normal tissues,as well as in various CRC cell lines.High expression of miR-188 was strongly associated with advanced tumor stage,accompanied with significant tumor cell proliferation,invasion and migration.It was confirmed that FOXL1 played positive crosstalk between miR-188 regulation and downstream Wnt/β-catenin signaling activation.Conclusions:All findings indicate that miR-188 promotes CRC cell proliferation and invasion through targeting FOXL1/Wnt signaling and could be served as a potential therapeutic target for human CRC in the future.

A safe and effective surgical navigation technique in laparoscopic radical gastrectomy: Indocyanine green-mediated near-infrared fluorescent imaging

In the past decades,gastric cancer(GC)is one of the most common cancers and causes of cancer-related deaths worldwide[1].China has the highest incidence of GC[2]and accounts for more than 40%of all new GC cases in the world[3].Radical lymphadenectomy serves as an important role in the staging and definitive management of GC[4,5].At present,laparoscopic radical gastrectomy has been shown to significantly improve the accuracy of tumor staging and long-term survival of GC patients[6].The retrieval of more lymph nodes(LNs)via lymphadenectomy is a current requirement for laparoscopic radical gastrectomy[5].Lymphadenectomy is usually performed according to the experience of surgeons.However,it is a substantial challenge for surgeons to efficiently and accurately acquire enough LNs without increasing the risk of complications as the vascular and lymphatic anatomy of stomach is extremely complex.Therefore,surgeons are looking for more accurate strategies to perform adequate lymphadenectomy under laparoscopic guidance.

m^(6)A-mediated regulation of PBX1-GCH1 axis promotes gastric cancer proliferation and metastasis by elevating tetrahydrobiopterin levels

Background:Methyltransferase 3(METTL3)-mediated N6-methyladenosine(m^(6)A)RNA modification has been demonstrated to be a potential factor in promoting gastric cancer(GC).METTL3 regulates a series of signaling pathways by modifying various mRNAs.This study aimed to identify novel METTL3-mediated signaling pathways and explored possible targets for use in the clinical setting of gastric cancer.Methods:To investigate the proliferation and metastatic capacity ofGCcell lines with METTL3 knockdown,a xenograft,lung metastasis,and popliteal lymph node metastasis model was used.Them^(6)A-modified RNA immunoprecipitation(Me-RIP)sequence was utilized to explore the target mRNAs of METTL3.Cell counting kit 8 and transwell assays were performed to investigate the promoting function of pre-B cell leukemia homeobox 1(PBX1)and GTP cyclohydrolase 1(GCH1).Western blotting and chromatin immunoprecipitation were employed to confirm the involvement of the METTL3-PBX1-GCH1 axis.ELISA and liquid chromatography-mass spectrometry were used to explore the biological function of tetrahydrobiopterin(BH_(4)).Results:Knockdown of METTL3 suppressed xenograft tumor growth and lung/lymph node metastasis in vivo.Mechanistically,we found that METTL3 combined with and stabilized PBX1 mRNAs.Chromatin immunoprecipitation(ChIP)and further experiments suggested that PBX1 acted as a transcription factor inducing GCH1 expression.Moreover,the METTL3-PBX1-GCH1 axis increased BH_(4)levels in GC cells,thereby promoting tumor progression.Conclusions:This study suggested that METTL3 enzymes promote tumor growth and lung/lymph node metastasis via METTL3-PBX1-GCH1 axis increasing BH_(4)levels in GC.

Aspirin-based chemoprevention of colorectal cancer: The role for gut microbiota

MAIN TEXT Despite improvements in the surveillance,diagnosis,and multimodal therapies for colorectal cancer(CRC),its mortality is persistently high worldwide[1-3].Continuing efforts for controlling CRC using similar strategies seems not sufficient given the persistent threats of CRC on human health.Prevention,in the form of chemoprevention,may provide another cost-effective way to enhance the outcomes of individuals at risk of developing CRC.In this regard,aspirin is emerging as a promising agent in the chemoprevention of CRC,especially for those at risk of cardiovascular diseases.However,the overall efficacy(∼30%)reported from multiple randomized controlled trials is still limited[4-6].The reasons for the limited efficacies of aspirin are elusive.Genetic and epigenetic factors are thought to be critical in relation to drug responses[7,8].