Purpose. Intratumor metabolic heterogeneity parameters on 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) have been proven to be predictors of the clinical prognosis of cancer patients. The study aimed to examine the correlation between 18F-FDG PET-CT-defined heterogeneity parameters and the prognostic significance in patients with colorectal cancer. Methods. The study included 188 patients with colorectal cancer who received surgery and 18F-FDG PET/CT examinations. Preoperative 18F-FDG PET/CT conventional and metabolic heterogeneity parameters were collected, including maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), heterogeneity index-1 (HI-1) and heterogeneity index-2 (HI-2), and clinicopathological information. Correlations between these parameters and patient survival outcomes were inferred. Results. The associations between 18F-FDG PET/CT parameters and clinical outcomes were analyzed. Tumor thrombus ( P < 0.001 ), tumor stage ( P = 0.001 ), MTV ( P = 0.003 ), HI-1 ( P = 0.032 ), and HI-2 ( P = 0.001 ) differed between the two groups with and without recurrence. Multivariate analysis showed that, in the radical surgery group, HI-2 (HR = 1.10, 95% CI: 1.04–1.17, P = 0.001 ), tumor stage (HR = 20.65, 95% CI: 4.81–88.62, P < 0.001 ), and regional lymph nodes status (HR = 0.16, 95% CI: 0.04–0.57, P = 0.005 ) were independent variables significantly correlated with progression-free survival (PFS) and HI-2 (HR = 1.16, 95% CI: 1.07–1.26, P < 0.001 ) was an independent variable affecting overall survival (OS). In the palliative surgery group, HI-2 (HR = 1.03, 95% CI: 1.01–1.06, P = 0.020 ) was an independent variable affecting PFS, and all the parameters were not statistically significant for OS. Conclusion. HI-2, tumor stage, and regional lymph nodes status might predict the outcomes of colorectal cancer more effectively than other 18F-FDG PET/CT defined parameters.

Background:The tumor suppressor role of tissue factor pathway inhibitor 2 (TFPI-2) has been reported in various tumors. The present study aimed to improve the understanding of the oncogenic properties of TFPI-2 in gastric cancer. Methods:Relative expression of TFPI-2 was determined by a real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell viability was measured via a cell counting kit-8 assay and proliferation was evaluated by a colony formation assay. Cell apoptosis was assessed with a caspase-3 activity kit and invasion was evaluated by a transwell chamber assay. The methylation level of TFPI-2 promoter was assayed by methylation-specific PCR. The regulatory effect of miR-27a-3p on TFPI-2 was analyzed with a luciferase reporter assay. The direct association between miR-27a-3p and TFPI-2 was shown by biotin-labelling pulldown.Results: TFPI-2 was down-regulated in gastric cancer, which associated with an unfavorable prognosis clinically. Ectopic introduction of TFPI-2 greatly compromised cell viability, colony formation and invasive capacity, and also induced cell apoptosis simultaneously. The promoter region of TFPI-2 was extensively methylated in gastric cancer tissues compared to normal tissues, suggesting the epigenetic inhibition of TFPI-2 expression. We further identified that TFPI-2 functioned as sponge RNA against miR-27a-3p. Most importantly, miR-27a-3p-specific inhibitor significantly exerted a tumor suppressor function akin to TFPI-2 itself, and the anti-tumoral activities were completely abolished by TFPI-2 knockdown. Conclusions:We found that the epigenetically suppressed TFPI-2 compromised sponging effects with respect to miR-27a-3p in gastric cancer, which consequently and mechanistically contributed to the tumor biology of gastric cancer. K E Y W O R D Sgastric cancer, methylation, miR-27a-3p, TFPI-2 Geng and Liu contributed equally to this work.

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Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recent studies have demonstrated that lncRNAs play an important role in tumorigenesis. LINC01291 has been confirmed to be involved in the proliferation and migration of different cancers, although the function of LINC01291 in HCC is still unknown.Methods: First, the expression of LINC01291 in 50 paired HCC tissues, adjacent normal tissues and HCC cell lines was measured by a quantitative real-time polymerase chain reaction. Then, the function of LINC01291 in HCC cell proliferation, migration and invasion was measured by colony formation, Cell Counting Kit-8 assays, wound healing assays and transwell assays. In addition, E-cadherin, N-cadherin, vimentin and oxidative stress-responsive 1 (OXSR1) protein expression levels were assessed via western blotting. Luciferase reporter assays were used to confirm the relationship between LINC01291 and miR-186-5p, as well as miR-186-5p and OXSR1 mRNA.Rescue assays and in vivo experiments further confirmed the LINC01291/miR-186-5p/OXSR1 axis in the progression of HCC.Results: LINC01291 was upregulated in both HCC tissues and cell lines. Knockdown of LINC01291 inhibited the proliferation, migration, invasion and epithelialmesenchymal progression (EMT) of HCC cells. In addition, LINC01291 could overexpress OXSR1 by sponging miR-186-5p, and OXSR1 overexpression or miR-186-5p inhibition could rescue the effect of LINC01291 knockdown in YY-8103 cell lines. In addition, lentiviral sh-LINC01291 could effectively inhibit the growth of subcutaneous YY-8103 xenograft tumors, whereas the anticancer effect could be reversed by cotransfection with in-miR-186-5p or ov-OXSR1.Conclusions: LINC01291 can promote the proliferation, migration, invasion and EMT of HCC cells via the miR-186-5p/OXSR1 axis, and sh-LINC01291 can inhibit tumor growth in a xenograft mouse model. Highlights• LINC01291 is upregulated in HCC by database and a qRT-PCR.• LINC01291 can promote the development of HCC by regulating the miR-186-5p/OXSR1 axis.Jian Chu, Guangyong Geng and Xiaoming Ai contributed equally to this work.

PurposeWe explored the predictive effect of intratumor metabolic heterogeneity indices extracted from 18F-FDG PET/CT on recurrence in stage II/III colorectal cancer after radical surgery.MethodsA total of 140 stage II/III colorectal cancer patients who received preoperative 18F-FDG PET/CT and radical resection were enrolled. 18F-FDG traditional parameters including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) under different thresholds; heterogeneity indices including the coefficient of variation with SUV 2.5 as a threshold (CV2.5), CV40%, heterogeneity index-1 (HI-1) calculated by the fixed-threshold method, and HI-2 calculated by the percentage threshold method; and clinicopathological information were collected. We concluded that relationships exist between these data and patients’ disease-free survival (DFS).ResultsRegional lymph node status (P &lt; 0.001), nerve invasion (P = 0.036), tumor thrombus (P = 0.005), and HI-1 (P = 0.010) exhibited significant differences between the relapse and non-relapse groups, while SUVmax, MTV2.5, MTV40%, TLG2.5, TLG40%, CV2.5, CV40%, HI-2, and other clinicopathological factors had no differences between the relapse and non-relapse groups. Multivariate analysis demonstrated that HI-1 (HR = 1.02, 1.00–1.04, P = 0.038), regional lymph node metastasis (HR = 2.95, 1.37–6.38, P = 0.006), and tumor thrombus status (HR = 2.37, 1.13–4.99, P = 0.022) were independent factors significantly related to DFS.ConclusionHI-1, tumor thrombus status, and regional lymph node status could predict the recurrence of stage II/III colorectal cancer after radical resection and had an advantage over other 18F-FDG PET/CT conventional parameters and heterogeneity indices.