Nomogram Models for Predicting Risk and Prognosis of Newly Diagnosed Ovarian Cancer Patients with Liver Metastases - A Large Population-Based Real-World Study.

Background: Previous studies about liver metastases (LM) in newly diagnosed ovarian cancer (NDOC) patients based on Surveillance, Epidemiology, and End Results (SEER) program disregarded selection bias of missing data. Methods: We identified Data of NDOC patients from SEER between 2010 and 2016, presented a comprehensive description of this dataset, and limited possible biases due to missing data by applying multiple imputation (MI). We determined predictive factors for underlying LM development in NDOC patients and evaluated prognostic factors in NDOC patients with LM (OCLM). We then established predictive nomograms, assessed by the concordance index, calibration curve, decision curve analysis (DCA), and clinical impact curves (CIC). Results: The amount of missing data for different variables in SEER dataset ranges from 0 to 36.11%. The results between complete dataset and MI datasets are similar. LM prevalence in NDOC patients was 7.18%, and median overall survival for OCLM patients was 11 months. The C-index of risk nomogram for LM development in the training cohort (TC) and validation cohort (VC) were 0.764 and 0.759, respectively. The C-index and integrated area under curve within five years of prognostic nomogram for OCLM patients in the TC and VC were 0.743 and 0.773, 0.714 and 0.733, respectively. For both nomograms, DCA revealed favorable clinical use and calibration curves suggested good consistency. Conclusion: The risk nomogram is expected to aid clinicians in identifying high-risk groups of LM development in NDOC patients for intensive screening. The prognostic nomogram could facilitate individualized prediction and stratification for clinical trials in OCLM patients.

[Analysis of gene expression patterns in an irinotecan-resistance colon cancer cell by cDNA microarray].

OBJECTIVE: To study the mechanism of irinotecan-resistant colon cancer by analyzing the differential gene expression patterns with cDNA microarray. METHODS: Total RNA was purified from irinotecan-sensitive colonic cancer cell line, SW480 and its irinotecan-resistance cell line, SW480/CPT. The cRNA retro-transcribed from RNA were labeled with Cy3 fluorescence as probes. The probes were hybridized with Agilent gene chips and the fluorescence images of the chips were obtained with Axon 4000B scanner as well as analyzed with Genepix 3.0 software. The microarray results were confirmed by reverse transcription-polymerase chain reaction. RESULTS: Of the 1598 genes with altered expressions, there were 911 up-regulated genes and 687 down-regulated genes. Glutathione S-Transferase (GST) isoenzyme family GSTA such as GSTA1, GSTA2, GSTA3 and GSTA5 were significantly up-regulated. The expression levels of many Zinc finger protein family members (ZNF) were also differentially regulated. CONCLUSION: GSTA and ZNF subunit genes might play an important regulation role in the irinotecan resistance of colon cancer.

[Cultivation and characterization of tumor spheres generated from human colorectal cancer cell lines].

OBJECTIVE: To study on the cultivation method for tumor spheres from colorectal cancer cell lines and identify whether resulting Colo205 spheroid cells display cancer stem cell characteristics. METHODS: Lovo, Colo205 and SW480 cells were seeded in serum free medium (SFM) with EGF and bFGF. Flow cytometry analysis, cell invasion assay and xenograft experiment were applied to examine the cell surface marker expression pattern, cell invasive ability and in vivo tumorigenicity of both Colo205 spheres and parental cells. CD44 expression of tumor spheroid cells was also analyzed after cultured with serum supplemented medium by flow cytometry. CD44, Musashi-1 and Oct4 mRNA were detected in these two cells by RT-PCR. RESULTS: Tumor spheres could be generated from three colorectal cancer cell lines in SFM. The formation and proliferation of tumor spheres were benefited from fresh SFM, cell dissociation reagent Accutase and the floating status of cancer cells. The overwhelming majority of spheroid cells were CD44+ cells. But CD44+ cells were gradually decreased when spheres cultured with serum supplemented medium. Colo205 spheres have higher Musashi-1 and Oct4 mRNA expression, tumor-initiating capability and invasive ability compared with those of parental cells. CONCLUSION: Tumor spheres in which enrich cancer stem cells can be generated and matained from colorectal cancer cell lines in SFM on floating-culture condition.

[The effect of Rac1 siRNA on the biological behaviors of gastrointestinal cancer cells].

OBJECTIVE: To explore the effect of Rac1 siRNA on the expression of Rac1 and the biological behaviors of gastrointestinal cancer cells. METHODS: Rac1 siRNA was transfected into human gastric cancer cell line SGC803 and colorectal cancer cell line Lovo by lipofectamine 2000. The expression of Rac1 in these cell lines were detected by Western blot and RT-PCR after 48 hours of the transfection. The effect of Rac1 on the proliferation of human gastric cancer cell line SGC803 and colorectal cancer cell line Lovo were tested by CCK8 kit. The motility of the transfected and the control cancer cells were assessed by Wound-healing assay and invasion assay. The apoptotic index was evaluated by Hoechst 33258 staining and FCM. RESULTS: Rac1 siRNA can down-regulated the expression of Rac1 on human gastric cancer cell line SGC803 and colorectal cancer cell line Lovo remarkably, and Rac1 siRNA can inhibit both the proliferation and motility of the transfectants. Analysis of apoptosis demonstrated that Rac1 siRNA can promote apoptosis of the gastric cancer cells and colorectal cancer cells. CONCLUSION: Rac1 play an important role in the regulation of biological behaviors of human gastric cancer and colorectal cancer cells, and the interference of Rac1 expression could provide a novel path in reversing the malignant phenotypes of these malignancies.