Prediction value of 18F-FDG PET/CT intratumor metabolic heterogeneity parameters for recurrence after radical surgery of stage II/III colorectal cancer.

Purpose: We 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. Methods: A 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). Results: Regional lymph node status (P < 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. Conclusion: HI-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.

Correlation between 18F-FDG PET/CT intra-tumor metabolic heterogeneity parameters and KRAS mutation in colorectal cancer.

PURPOSE: The study aimed to evaluate the relationship between intra-tumor metabolic heterogeneity parameters of 18F-FDG and KRAS mutation status in colorectal cancer (CRC) patients and which threshold heterogeneity parameters could better reflect the heterogeneity characteristics of colorectal cancer. METHODS: Medical data of 101 CRC patients who underwent 18F-FDG PET/CT and KRAS mutation analysis were selected. On PET scans, 18F-FDG traditional indices maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity parameters coefficient of variation with a threshold of 2.5 (CV2.5), CV40%, heterogeneity index-1 (HI-1), and HI-2 of the primary lesions were obtained. We inferred correlations between these 18F-FDG parameters and KRAS mutation status. RESULTS: 41 patients (40.6%) had KRAS gene mutation. Assessment of FDG parameters showed that SUVmax (19.00 vs. 13.16, p < 0.001), MTV (11.64 vs. 8.83, p = 0.001), and TLG (102.85 vs. 69.76, p < 0.001), CV2.5 (0.55 vs. 0.46, p = 0.006), and HI-2 (14.03 vs. 7.59, p < 0.001) of KRAS mutation were higher compared to wild-type (WT) KRAS. CV40% (0.22 vs. 0.24, p = 0.001) was lower in the KRAS mutation group, while HI-1 had no significant difference between the two groups. Multivariate analysis showed that MTV (OR = 4.97, 1.04-23.83, p = 0.045) was the only significant predictor in KRAS mutation, using a cut-off of 7.62 (AUC = 0.695), and MTV showed a sensitivity of 90.2% and specificity of 45.0%. However, the PET parameters were not independent predictors in KRAS mutation. CONCLUSION: KRAS gene mutant CRC patients had more 18F-FDG uptake (SUVmax, MTV, TLG) and heterogeneity (CV2.5, HI-2) than WT KRAS. MTV was the only independent predictor of KRAS gene mutation in colorectal cancer patients.

Prognostic Value of Intratumor Metabolic Heterogeneity Parameters on 18F-FDG PET/CT for Patients with Colorectal Cancer.

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.

LINC01291 promotes hepatocellular carcinoma development by targeting the miR-186-5p/OXSR1 axis.

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 epithelial-mesenchymal 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.

Low abundance of TFPI-2 by both promoter methylation and miR-27a-3p regulation is linked with poor clinical outcome in gastric cancer.

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.

Expression of tissue factor pathway inhibitor 2 in human pancreatic carcinoma and its effect on tumor growth, invasion, and migration in vitro and in vivo.

Tissue factor pathway inhibitor 2 (TFPI-2), also known as placental protein and matrix-associated serine protease inhibitor, plays an important role in angiogenesis, intravascular fibrinolysis, wound healing, tumor invasion, metastasis by plasmin, and trypsin mediated activation of zymogen matrix metalloproteinases. To detect whether TFPI-2 can be expressed in human pancreatic carcinoma samples and to investigate its role in the growth, invasion, and metastasis of pancreatic carcinoma cell in vitro and in vivo, we collected eight normal pancreatic tissue samples and 50 pancreatic carcinoma samples, and stably transfected the human pancreatic carcinoma cell line Panc-1 with a vector capable of expressing TFPI-2 gene. RT-PCR and Western blot analysis revealed that the levels of TFPI-2 expression were markedly lower in pancreatic carcinoma samples compared with normal pancreas samples. The level of TFPI-2 protein was significantly higher in cells transfected with TFPI-2 gene than that in the untransfected cells. The results of MTT assay showed that TFPI-2 inhibited Panc-1 cells growth in vitro. The invasive capacity of the cells transfected with TFPI-2 gene was also markedly less than that of untransfected cells in vitro as determined by the Matrigel invasion/migration assay. Moreover, TFPI-2 inhibited tumor growth, invasion, and metastasis in vivo in an orthotopic pancreatic carcinoma model. Our findings suggest that TFPI-2 plays a significant role in the growth, invasion, and metastasis of pancreatic carcinoma cell in vitro and in vivo, and has potential in anticancer therapy.

Prognostic significance of tissue factor pathway inhibitor-2 in pancreatic carcinoma and its effect on tumor invasion and metastasis.

Tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated kunitz-type serine proteinase inhibitor that plays an important role in plasmin and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor angiogenesis, invasion and metastasis. Earlier studies have shown that the production of TFPI-2 is downregulated during the progression of various tumors. To detect whether TFPI-2 can be expressed in human pancreatic carcinoma samples, to evaluate its prognostic significance on pancreatic carcinoma and to investigate its effect on tumor invasion and metastasis, we collected 9 normal pancreatic tissue samples and 41 pancreatic carcinoma samples and stably transfected the human pancreatic carcinoma cell line Panc-1 with a vector capable of expressing TFPI-2 gene. RT-PCR and Western blot analysis revealed that the expression of TFPI-2 in pancreatic carcinoma samples was markedly lower than that in normal pancreas samples, and there was no TFPI-2 expression in Panc-1 cell. Its expression was related with biological characters of pancreatic carcinoma. The results of Boyden chamber assay and orthotopic pancreatic carcinoma model showed that TFPI-2 could inhibit invasion and metastasis ability of pancreatic carcinoma in vitro and in vivo. Kaplan-Meier survival curve and Cox proportional hazards model assay identified TFPI-2 as an independent prognostic factor for pancreatic carcinoma. Our data suggest that TFPI-2 plays a significant role in the invasion and metastasis of pancreatic carcinoma cell in vitro and in vivo and is determined to be an important prognostic factor for pancreatic carcinoma patients.