Analysis of IGFBP7 expression characteristics in pan-cancer and its clinical relevance to stomach adenocarcinoma.

Background: Insulin-like growth factor (IGF) binding proteins (IGFBPs) are involved in tumorigenesis and cancer progression. IGFBP7 has been shown to act as either a tumor suppressive gene or an oncogene in many tumors, including stomach adenocarcinoma (STAD). To provide a more systematic and comprehensive understanding of IGFBP7 gene, we performed an integrative pan-cancer analysis and explored further with the case of STAD. Methods: We compared the expression data of IGFBP7 in various cancer and normal tissues obtained from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database. The TISIDB web portal was used to analyze the associations of IGFBP7 with cancer molecular subtypes and immune subtypes. We also analyzed the predictive ability and prognostic values of IGFBP7 in pan-cancer, as well as explored its targeted binding proteins and their biological functions. Additionally, we examined the relationship between IGFBP7 and the clinical characteristics of STAD, investigated the co-expression genes and biological functions of differentially expressed genes (DEGs), and validated the mRNA and protein expression levels of IGFBP7 using gastric cancer (GC) and adjacent normal tissues in a small self-case-control study. Results: IGFBP7 was found to be overexpressed in STAD and downregulated in many other cancers. The mRNA and protein expression levels of IGFBP7 were also significantly higher in the collected GC tissues compared with adjacent tissues. Expression of IGFBP7 varied significantly across molecular subtypes of nine different cancer types and immune subtypes of eight types, with the highest expression observed in the genomically stable molecular subtype and C3 inflammatory immune subtype in STAD. IGFBP7 demonstrated an area under the curve (AUC) >0.7 for predicting 16 cancer types, and an AUC >0.9 for seven types. Patients in the higher IGFBP7 expression group showed a poorer prognosis for adrenal cortical carcinoma (ACC) and low-grade glioma (LGG), while demonstrating a more favorable prognosis for kidney renal clear cell carcinoma (KIRC). IGFBP7 expression in STAD was significantly associated with T stage, pathological stage, histologic grade, and Helicobacter pylori infection. Conclusions: IGFBP7 showed promise as a biomarker for prediction and prognosis in pan-cancer. IGFBP7 was found to be overexpressed in STAD, and its expression was closely associated with the clinical characteristics of STAD.

Development and Validation of Prognostic Nomograms Based on Lymph Node Ratio for Young Patients with Gastric Cancer: A SEER-Based Study.

PURPOSE: To investigate the role of lymph node ratio (LNR) in young patients with gastric cancer (GC) and develop nomograms to predict the survival of young GC patients. METHODS: This retrospective study enrolled stage I-III GC patients before the age of 40 between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards models were used to determine the prognosticators and create the nomograms incorporating LNR to predict overall survival (OS) and cancer-specific survival (CSS). The discriminating superiority of the nomograms was examined using calibration curves, C-index, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and integrated discrimination improvement (IDI) by comparing with the TNM staging. The performance of the nomograms for risk stratification was analyzed by the Kaplan-Meier method. RESULTS: Based on the significant prognosticators identified in multivariate survival analysis, the nomograms were established and showed LNR as the third strongest predictor. The C-index of the nomograms for OS and CSS were higher than those of the TNM staging (OS: 0.773 vs 0.665; CSS: 0.769 vs 0.666). The ROC curves for the nomograms to predict survival exhibited superior sensitivity and specificity when compared with the TNM staging. The calibration plots, DCA curves, and IDI values of the nomograms also demonstrated adequate fit and ideal net benefit in prediction and clinical utility. The Kaplan-Meier analysis observed remarkable differences in patients divided into different risk subgroups (P < .001). CONCLUSIONS: These results found the clinical outperformance of the LNR-based nomograms for predicting survival in young stage I-III GC patients. Our nomograms may improve accuracy of survival risk prediction and facilitate individualized care of young stage I-III GC patients.

HKDC1 upregulation promotes glycolysis and disease progression, and confers chemoresistance onto gastric cancer.

There is increasing evidence that hexokinase is involved in cell proliferation and migration. However, the function of the hexokinase domain containing protein-1 (HKDC1) in gastric cancer (GC) remains unclear. Immunohistochemistry analysis and big data mining were used to evaluate the correlation between HKDC1 expression and clinical features in GC. In addition, the biological function and molecular mechanism of HKDC1 in GC were studied by in vitro and in vivo assays. Our study indicated that HKDC1 expression was upregulated in GC tissues compared with adjacent nontumor tissues. High expression of HKDC1 was associated with worse prognosis. Functional experiments demonstrated that HKDC1 upregulation promoted glycolysis, cell proliferation, and tumorigenesis. In addition, HKDC1 could enhance GC invasion and metastasis by inducing epithelial-mesenchymal transition (EMT). Abrogation of HKDC1 could effectively attenuate its oncogenic and metastatic function. Moreover, HKDC1 promoted GC proliferation and migration in vivo. HKDC1 overexpression conferred chemoresistance to cisplatin, oxaliplatin, and 5-fluorouracil (5-Fu) onto GC cells. Furthermore, nuclear factor kappa-B (NF-κB) inhibitor PS-341 could attenuate tumorigenesis, metastasis, and drug resistance ability induced by HKDC1 overexpression in GC cells. Our results highlight a critical role of HKDC1 in promoting glycolysis, tumorigenesis, and EMT of GC cells via activating the NF-κB pathway. In addition, HKDC1-mediated drug resistance was associated with DNA damage repair, which further activated NF-κB signaling. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.

Clinical features of capsule endoscopy in young adults: A single-center retrospective study.

Background and Aim: Capsule endoscopy (CE) has been used in clinical examination among people of various ages, while few studies exclusively focused on the young. We aimed to explore its clinical features in young adults and those with obscure gastrointestinal bleeding (OGIB). Methods: A total of 479 young adults aged 18-44 years were analyzed, with median age of 33 years. Primary positive findings of patients were classified into four kinds of lesions, and potential risk of bleeding among patients with OGIB was assessed based on Saurin classification (P0-2 lesions). Results: The overall completion rate and diagnostic yield of CE among young adults were 89.77 and 77.04%, respectively. Significant differences were found among overall completion rate/diagnostic yield and inpatient status/CE brand. Positive diagnostic yield among 157 patients with OGIB was 51.59% (P1-2 lesions), and the significant risk of bleeding was 37.04% (P2 lesions). Among patients with OGIB in which 134 patients with a total of 216 lesions, ulceration was the commonest P2 lesions, followed by angioectasia and telangiectasia. Inpatient rate, completion rate, and diagnostic yield were higher among patients with overt OGIB, and disease categories of overt OGIB were different compared with occult OGIB. Conclusion: CE is an optimal tool for discovering lesions in young adults and could play a role in evaluating the bleeding risk of young adults with OGIB.

Diagnostic and prognostic value of HOXC family members in gastric cancer.

Aims: HOX clusters encode proteins that play pivotal roles in regulating transcription factors and many other proteins during embryogenesis. However, little is known about the diagnostic and prognostic values of HOXC family members in gastric cancer (GC). Materials and methods: The authors evaluated the data in patients with GC based on bioinformatics analysis. Results: HOXC6/8/9/10/11/13 were overexpressed in GC and associated with a poor prognosis. HOXC4/5 were downregulated in GC tissues. Receiver operating characteristic curve analysis demonstrated that they have high diagnostic value. In addition, HOXC4/5/6/9/10/11/13 were negatively correlated with DNA methylation level. The gene set enrichment analysis results implied that they play essential roles in multiple biological processes underlying tumorigenesis. Conclusion: HOXC family members are potential targets for diagnosis and may work as prognostic biomarkers of GC.

Lay abstracts Gastric cancer (GC) remains one of the most common malignant tumors of the digestive system and the third most common cause of death from cancer. Since GC is usually diagnosed at an advanced stage, despite advances in comprehensive treatment strategies, its mortality rate is still very high. GC is a disease that is highly heterogeneous in terms of genotype and phenotype. Therefore, a more complete understanding of the molecular mechanism of GC carcinogenesis and identification of reliable molecular targets for the diagnosis and prognosis of GC are highly valued. It is well known that the HOXC gene family expression is upregulated in most solid tumor types, such as lung cancer, colon cancer and prostate cancer. The authors explore the role of the HOXC gene family in GC. Results demonstrated that HOXC family members are potential targets for diagnosis and may work as prognostic biomarkers of GC.

Prognostic performance of different lymph node classification systems in young gastric cancer.

BACKGROUND: Accurate staging plays a pivotal role in cancer care. The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been suggested as alternatives to the N staging since the TNM system has the risk of stage migration. The prognostic significance of LNR and LODDS in young patients with gastric cancer (GC) has not been reported. This study aims to investigate the correlations between LNR and LODDS and survival of young patients with GC, and compare the predictive performance of these LN staging methods. METHODS: GC patients before the age of 40 from 2004 to 2016 in the Surveillance, Epidemiology and End Results database were enrolled. The prognostic evaluation of the N factor, LNR and LODDS was compared using the time-dependent receiver operating characteristic (ROC) analysis, area under the curve (AUC), C-index and Akaike information criterion (AIC). RESULTS: Multivariate survival analysis identified that the LNR and LODDS were significantly independent prognostic indicators for overall survival (OS) in young patients with GC and in the subgroups comprised of patients with ≤15 LNs examined. The time-dependent ROC curves of the LNR and LODDS were continuously superior to that of the N factor in predicting OS during the observation period. And the AUCs revealed that the predictive accuracy of the LNR and LODDS was remarkably superior to the N factor at 1 and 3 years (P<0.05). The model incorporating LNR or LODDS had higher C-index and lower AIC when comparing to the model incorporating the N factor. CONCLUSIONS: The LNR and LODDS improve accuracy of survival risk prediction in young patients with GC when comparing to the N factor. These two novel LN classification methods should be considered as alternatives to the N staging for the prognostic prediction of young patients with GC.

Prognostic significance and function of MCM10 in human hepatocellular carcinoma.

Aim: To investigate the role of MCM10, a conserved replication factor, in hepatocellular carcinoma (HCC). Methods: We used data from 364 HCC patients in the Cancer Genome Atlas database and conducted in vitro experiments to confirm the role of MCM10. Results: High MCM10 expression correlated with poor HCC patient outcome and was an independent prognosticator for HCC. Time-dependent receiver operating characteristic curve analysis found that the sequential trend of MCM10 for survival was not inferior to that of the tumor node metastasis stage. The MCM10 model had a higher C-index than the non-MCM10 model, indicating that incorporating MCM10 into a multivariate model improves the model's prognostic accuracy for HCC. Genetic alterations of MCM10 prominently correlated with an unfavorable HCC outcome. Conclusion: Our findings strongly suggest using the MCM10 gene as a prognostic indicator in HCC.

Lay abstract Hepatocellular carcinoma is one of the most aggressive malignant cancers globally. Our study investigated the role of a conserved replication factor, MCM10, in hepatocellular carcinoma. We performed some bioinformatics analysis and in vitro experiments, and successfully found that MCM10 has a good predictive value for survival in patients with hepatocellular carcinoma.

HOTAIR plays an oncogenic role in gastric cancer through microRNA and SNP.

HOX transcript antisense intergenic RNA (HOTAIR) is a lncRNA with a length of 2,158 nucleotides and its two terminal domains could combine with different complexes to function at the level of transcription and translation. It overexpresses in many cancers including gastric cancer. HOTAIR could play an oncogenic role in the initiation and progression of gastric cancer through interaction with microRNAs, such as miR-330/618/126 in the PI3K/Akt signaling pathways. HOTAIR single nucleotide polymorphisms (SNPs) may have genotype-function and allele-specific effect on gastric cancer by a mechanism that specific SNP could give rise to a variation of HOTAIR and alter the binding site of microRNAs. Both rs920778 T allele and rs4759314 G allele will enhance the susceptibility to gastric cancer in the Chinese populations. In a word, the suppression of HOTAIR and overexpression of downstream microRNAs may be potential therapeutic strategies of gastric cancer related to HOTAIR.