Identification of key genes controlling cancer stem cell characteristics in gastric cancer

BACKGROUND Self-renewal of gastric cancer stem cells(GCSCs)is considered to be the underlying cause of the metastasis,drug resistance,and recurrence of gastric cancer(GC).AIM To characterize the expression of stem cell-related genes in GC.METHODS RNA sequencing results and clinical data for gastric adenoma and adenocarcinoma samples were obtained from The Cancer Genome Atlas database,and the results of the GC mRNA expression-based stemness index(mRNAsi)were analyzed.Weighted gene coexpression network analysis was then used to find modules of interest and their key genes.Survival analysis of key genes was performed using the online tool Kaplan-Meier Plotter,and the online database Oncomine was used to assess the expression of key genes in GC.RESULTS mRNAsi was significantly upregulated in GC tissues compared to normal gastric tissues(P<0.0001).A total of 16 modules were obtained from the gene coexpression network;the brown module was most positively correlated with mRNAsi.Sixteen key genes(BUB1,BUB1 B,NCAPH,KIF14,RACGAP1,RAD54 L,TPX2,KIF15,KIF18 B,CENPF,TTK,KIF4 A,SGOL2,PLK4,XRCC2,a n d C1 orf112)were identified in the brown module.The functional and pathway enrichment analyses showed that the key genes were significantly enriched in the spindle cellular component,the sister chromatid segregation biological process,the motor activity molecular function,and the cell cycle and homologous recombination pathways.Survival analysis and Oncomine analysis revealed that the prognosis of patients with GC and the expression of three genes(RAD54 L,TPX2,and XRCC2)were consistently related.CONCLUSION Sixteen key genes are primarily associated with stem cell self-renewal and cell proliferation characteristics.RAD54 L,TPX2,and XRCC2 are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.

Nine-long non-coding ribonucleic acid signature can improve the survival prediction of colorectal cancer

BACKGROUND Investigating molecular biomarkers that accurately predict prognosis is of considerable clinical significance.Accumulating evidence suggests that long noncoding ribonucleic acids(lncRNAs)are frequently aberrantly expressed in colorectal cancer(CRC).AIM To elucidate the prognostic function of multiple lncRNAs serving as biomarkers in CRC.METHODS We performed lncRNA expression profiling using the lncRNA mining approach in large CRC cohorts from The Cancer Genome Atlas(TCGA)database.Receiver operating characteristic analysis was performed to identify the optimal cutoff point at which patients could be classified into the high-risk or low-risk groups.Based on the Cox coefficient of the individual lncRNAs,we identified a ninelncRNA signature that was associated with the survival of CRC patients in the training set(n=175).The prognostic value of this nine-lncRNA signature was validated in the testing set(n=174)and TCGA set(n=349).The prognostic models,consisting of these nine CRC-specific lncRNAs,performed well for risk stratification in the testing set and TCGA set.Time-dependent receiver operating characteristic analysis indicated that this predictive model had good performance.RESULTS Multivariate Cox regression and stratification analysis demonstrated that this nine-lncRNA signature was independent of other clinical features in predicting overall survival.Functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms further indicated that these nine prognostic lncRNAs were closely associated with carcinogenesis-associated pathways and biological functions in CRC.CONCLUSION A nine-lncRNA expression signature was identified and validated that could improve the prognosis prediction of CRC,thereby providing potential prognostic biomarkers and efficient therapeutic targets for patients with CRC.

Prognostic significance of the preoperative hemoglobin to albumin ratio for the short-term survival of gastric cancer patients

BACKGROUND Hemoglobin and albumin are associated with the prognosis of gastric cancer(GC)patients. However, the prognostic value of the hemoglobin to albumin ratio(HAR) for the short-term survival of GC patients with D2 radical resection has not been studied.AIM To investigate the significance of the HAR in evaluating the short-term survival of GC patients after D2 radical resection and to construct a nomogram to predict the prognosis in GC patients after surgery, thus providing a reference for the development of postoperative individualized treatment and follow-up plans.METHODS Cox regression and Kaplan-Meier analysis was used for prognostic analysis.Logistic regression was used to analyze the relationships between HAR and the clinicopathological characteristics of the GC patients. A prognostic nomogram model for the short-term survival of GC patients was constructed by R software.RESULTS HAR was an independent risk factor for the short-term survival of GC patients.GC patients with a low HAR had a poor prognosis(P < 0.001). Low HAR was markedly related to high stage [odds ratio(OR) = 0.45 for Ⅱ vs Ⅰ;OR = 0.48 for Ⅲ vs Ⅰ], T classification(OR = 0.52 for T4 vs T1) and large tumor size(OR = 0.51 for ≥4 cm vs < 4 cm)(all P < 0.05). The nomogram model was based on HAR, age,CA19-9, CA125 and stage, and the C-index was 0.820.CONCLUSION Preoperative low HAR was associated with short-term survival in GC patients.The prognostic nomogram model can accurately predict the short-term survival of GC patients with D2 radical resection.

西方T1期结直肠癌手术患者淋巴结转移的预测因素

背景:在西方人群中,T1期结直肠癌患者的淋巴结转移风险尚未被充分报道。本研究通过对T1期CRC患者的手术标本和人口学资料进行分析,探讨淋巴结转移的预测因素及患者的长期预后。方法:从SEER数据库中筛选出2004-2014年间行手术切除的T1期结直肠癌患者,排除多原发癌、接受新辅助治疗或无病理诊断者。采用多因素逻辑回归分析确定淋巴结转移的预测因素。结果:22,319例T1期结直肠癌患者淋巴结转移率为10.6%,其中N1期9.6%,N2期1.0%。低龄、女性、亚裔或非裔美国人、低分化癌和肿瘤位于直肠以外者,淋巴结转移率显著增高。在不同部位的肿瘤中,直肠癌淋巴结转移率最低(HR=0.74;95%CI 0.63–0.86)。结论:对于T1期结直肠癌患者,美国白人的淋巴结转移风险较亚裔或非裔美国人更低;直肠癌患者淋巴结转移风险较其他部位肿瘤更低。