Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity.

PURPOSE: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. MATERIALS AND METHODS: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). RESULTS: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. CONCLUSIONS: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Integrated Analysis of Gene Expression and Metabolite Data Reveals Candidate Molecular Markers in Colorectal Carcinoma.

Background: This study investigated potential gene targets and metabolite markers associated with colorectal carcinoma (CRC). Materials & Methods: Gene expression data (GSE110224) related with CRC were obtained from Gene Expression Omnibus, including 17 tumor tissues and 17 normal colon ones. The gene differential analysis, functional analysis, protein-protein interaction (PPI) analysis, and metabolite network construction were performed to identify key genes related to CRC. Moreover, an external dataset was used to validate genes of interest in CRC, and corresponding survival analysis was also conducted. Results: The authors extracted 197 differentially expressed genes (75 upregulated and 122 downregulated genes). Moreover, upregulated genes were closely associated with rheumatoid arthritis and amoebiasis pathways. The downregulated genes were mainly related to bile secretion and proximal tubule bicarbonate reclamation pathway. Combined with PPI network and metabolite prediction, the overlapped nine genes (CXCL1, CXCL8, CXCL10, HDS1782, IL18, PCK1, PTGS2, SERPINB2, TMP1) were found to be critical in CRC. Similar gene expression profiles of nine critical genes were validated by an external dataset, except for SERPINB2. In addition, the expressions of TIMP1, IL1B, and PTGS2 were closely related with prognosis. Finally, the metabolite network analysis revealed that there were close associations between prostaglandin E2 and three pathways (rheumatoid arthritis, amoebiasis, and leishmaniasis). Conclusion: CXCL1/CXCL8/IL1B/PTGS2-prostaglandin E2 axes were the potential signatures involved in CRC progression, which could provide new insights to understand the molecular mechanisms of CRC.

Concurrence of Gastric Cancer and Incidental Pulmonary Embolism May Be a Prognostic Factor for Advanced Gastric Cancer Patients with Incidental Pulmonary Embolism.

OBJECTIVE: Cancer is well known as the most important risk factor for the emergence of pulmonary embolism (PE). The incidence of incidental PE (IPE) has increased with widely use of multi-detector-row computed tomography (CT) technology. Simultaneously, more new cancer patients diagnosed concomitantly with IPE are found. No study has examined the presentation and prognosis of incidental pulmonary embolism (IPE) in gastric cancer patients. The aim of this study was to analyse prognostic factors in patients with advanced gastric cancer complicated with IPE. PATIENTS AND METHODS: Ninety patients with histologically confirmed advanced gastric adenocarcinoma diagnosed with IPE were enrolled. Continuous variables were compared using Student's t-test or the Mann-Whitney U-test if non-normally distributed. The Chi-squared test (or Fisher's exact test where appropriate) was used to compare categorical variables. The Kaplan-Meier method and the Log rank test were used for survival analysis. Independent prognostic factors for survival were determined using a Cox proportional hazards model. A two-sided P-value < 0.05 was considered statistically significant. RESULTS: Nineteen patients were diagnosed with IPE concomitantly with gastric cancer. Concurrence of gastric cancer and IPE, lack of anticoagulation therapy, and location of IPE were associated with survival. After adjusting for age and sex, the concurrence of gastric cancer and IPE, lack of anticoagulation, and central IPE independently influenced the survival of advanced gastric cancer patients with IPE. Subgroup analysis of patients with peripheral pulmonary embolisms confirmed that anticoagulant therapy provided a survival benefit. CONCLUSION: Concurrence of gastric cancer and IPE may be a prognostic factor for advanced gastric cancer patients with IPE.

Circular RNA PCDH10 regulates the tumorigenesis of pancreatic cancer through the miR-338-3p/hTERT axis.

Protocadherin-10 (PCDH10) was previously identified as a pancreatic cancer (PC) suppressor by reducing telomerase activity through binding with human telomerase reverse transcriptase (hTERT). However, we did not observe any effects of PCDH10 on hTERT mRNA or protein expression. Our research found that the PCDH10 gene could be transcribed into linear mRNA or circular RNA, and FUS could bind to the introns flanking the circularized exons, inducing the PCDH10 linear mRNA to shift to circPCDH10 in PC cells. Knockdown of circPCDH10 significantly inhibited PC progression. Mechanistically, circPCDH10 acted as a sponge of miR-338-3p, which could negatively regulate hTERT expression in PC cells. The inhibitory effects of circPCDH10 knockdown on PC cells could be notably reversed by miR-338-3p inhibition and ectopic expression of hTERT. Overall, we propose that the increased FUS expression in PC cells made circPCDH10 the preferred product of the PCDH10 gene, and circPCDH10 might promote PC progression through upregulation of hTERT expression by targeting miR-338-3p.

Outcomes of 596 Advanced Gastric Cancer Patients with Different Numbers of Chemotherapy Lines: The More Chemotherapy Lines, the Better Survival.

OBJECTIVE: Many large-sample prospective randomized clinical trials investigating advanced gastric cancer (AGC) have confirmed the survival advantages of first-line, second-line, or third-line chemotherapy compared with their respective control groups. However, due to the ethical concerns of prospective clinical trials, it is impossible to conduct a randomized comparative study of patients who do not receive chemotherapy and those who receive a second-line or above chemotherapy. Few research reports have addressed the relationship between the number of chemotherapy lines and overall survival (OS) in patients with AGC. In the present study, we analyzed the impact of the number of chemotherapy lines on OS in AGC patients using real-world data. PATIENTS AND METHODS: This study collected the medical records of patients with AGC diagnosed at Shandong Cancer Hospital from December 2007 to December 2017. According to the treatment received, AGC patients were divided into groups that did not receive chemotherapy, those who received only 1 line, 2 lines, or 3 lines and above. Kaplan-Meier analysis was used to assess patient survival. RESULTS: A total of 596 AGC patients were included in this study. The following patients were enrolled: 0 lines (did not receive chemotherapy), 77 (12.9%); 1 line, 235 (39.4%) patients; 2 lines, 185 (31.1%) patients; and ≥3 lines 99 (16.6%) patients. OS was significantly correlated with the number of chemotherapy lines (P<0.001), with a median OS from diagnosis of 3.3, 8.6, 15.6, and 21.0 months for patients receiving 0, 1, 2, ≥3 lines of chemotherapy, respectively. CONCLUSION: This study showed that the more chemotherapy lines AGC patients received, the longer the OS. This study not only confirmed the impact of chemotherapy lines on OS but it also supplements the results of prospective clinical trials that cannot be completed due to the ethical implications.