Combining pathological risk factors and T, N staging to optimize the assessment for risk stratification and prognostication in low-risk stage III colon cancer.

BACKGROUND: This study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future. PATIENTS AND METHODS: PRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan-Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation. RESULTS: Nine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004-7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158-5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953-17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623-13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317-6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858-5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613-2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731-2.033, P < 0.001). CONCLUSION: Combined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.

Construction and Validation of a Novel Prognosis Model in Colon Cancer Based on Cuproptosis-Related Long Non-Coding RNAs.

Colon cancer (CC) is one of the most common (6%) malignancies and leading cause of cancer-associated death (more than 0.5 million) worldwide, which demands reliable prognostic biomarkers. Cuproptosis is a novel modality of regulated cell death triggered by the accumulation of intracellular copper. LncRNAs have been reported as prognostic signatures in different types of tumors. However, the correlation between cuproptosis-related lncRNAs (CRLs) and CC remains unclear. Data of CC patients were downloaded from public databases. The prognosis-associated CRLs were identified by co-expression analysis and univariate Cox. Least absolute shrinkage and selection operator were utilized to construct the CRLs-based prognostic signature in silico for CC patients. CRLs level was validated in human CC cell lines and patient tissues. ROC curve and Kaplan-Meier curve results revealed that high CRLs-risk score was associated with poor prognosis in CC patients. Moreover, the nomogram revealed that this model possessed a steady prognostic prediction capability with C-index as 0.68. More importantly, CC patients with high CRLs-risk score were more sensitive to eight targeted therapy drugs. The prognostic prediction power of the CRLs-risk score was further confirmed by cell lines, tissues and two independent CC cohorts. This study constructed a novel ten-CRLs-based prognosis model for CC patients. The CRLs-risk score is expected to serve as a promising prognostic biomarker and predict targeted therapy response in CC patients.

A Novel m7G-Related Gene Signature Predicts the Prognosis of Colon Cancer.

Colon cancer (CC), one of the most common malignancies worldwide, lacks an effective prognostic prediction biomarker. N7-methylguanosine (m7G) methylation is a common RNA modification type and has been proven to influence tumorigenesis. However, the correlation between m7G-related genes and CC remains unclear. The gene expression levels and clinical information of CC patients were downloaded from public databases. Twenty-nine m7G-related genes were obtained from the published literature. Via unsupervised clustering based on the expression levels of m7G-related genes, CC patients were divided into three m7G clusters. Based on differentially expressed genes (DEGs) from the above three groups, CC patients were further divided into three gene clusters. The m7G score, a prognostic model, was established using principal component analysis (PCA) based on 15 prognosis-associated m7G genes. KM curve analysis demonstrated that the overall survival rate was remarkably higher in the high-m7G score group, which was much more significant in advanced CC patients as confirmed by subgroup analysis. Correlation analysis indicated that the m7G score was associated with tumor mutational burden (TMB), PD-L1 expression, immune infiltration, and drug sensitivity. The expression level of prognosis-related m7G genes was further confirmed in human CC cell lines and samples. This study established an m7G gene-based prognostic model (m7G score), which demonstrated the important roles of m7G-related genes during CC initiation and progression. The m7G score could be a practical biomarker to predict immunotherapy response and prognosis in CC patients.

Elevated preoperative CA125 is associated with poor survival in patients with metastatic colorectal cancer undergoing primary tumor resection: a retrospective cohort study.

Background: The impact of the preoperative carbohydrate antigen 125 (CA125) level on the survival of metastatic colorectal cancer (CRC) patients undergoing primary tumor resection (PTR) remains uncertain. The aim of this study was to assess the prognostic value in overall survival (OS) and cancer-specific survival (CSS) between patients with and without an elevated preoperative CA125 level. Methods: All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were retrospectively included. OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels. Results: Among 326 patients examined, 46 (14.1%) exhibited elevated preoperative CA125 levels and the remaining 280 (85.9%) had normal preoperative CA125 levels. Patients with elevated preoperative CA125 levels had lower body mass index, lower preoperative albumin level, lower proportion of preoperative chemotherapy, higher carcinoembryonic antigen and carbohydrate antigen 19-9 (CA19-9) levels, poorer differentiation, and more malignant histopathological type than patients with normal preoperative CA125 levels. In addition, patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages, more peritoneal metastasis, and more vessel invasion than patients with normal preoperative CA125 levels. Moreover, the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels. Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels. Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR. The hazard ratio (HR) in OS was 2.36 (95% confidence interval [CI], 1.67-3.33, P < 0.001) and the HR in CSS was 2.50 (95% CI, 1.77-3.55, P < 0.001). The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis. Conclusion: Based on an analysis of metastatic CRC patients undergoing PTR, an elevated preoperative CA125 level was associated with poor prognosis, which should be taken into consideration in clinical practice.

Effects of endometrial preparations and transferred embryo types on pregnancy outcome from patients with advanced maternal age.

We explored the strategy of frozen-thawed embryo transfer (FET) in the women with advanced maternal age (AMA). We first determined the age cut-off point of AMA by retrospective analysis of pregnancy outcomes in the patients undergoing FET. The patients with AMA were divided into 3 groups including natural cycle (NC) group, controlled ovarian stimulation (COS) group, and hormone replacement therapy (HRT) group, and simultaneously were divided into 2 groups including cleavage-stage embryo transfer (CET) group and blastocyst-stage embryo transfer (BET) group. The clinical pregnancy, embryo implantation, abortion and live birth rates were compared between the 3 groups and the 2 groups, respectively. We found that in the women aged 38 years or over, the clinical pregnancy rate and live birth rate were all significantly decreased as compared with the younger than 38-year-old women (all P < 0.05), so the women aged 38 years or over were regarded as the patients with AMA in this study. In the patients with AMA, the clinical pregnancy rate and live birth rate were 22.95% and 18.03% in NC group, 23.68% and 15.79% % in COS group as well as 24.58% and 15.92% in HRT group, and there were no significant differences in the clinical pregnancy rate and live birth rate between the 3 groups. However, the clinical pregnancy rate (42.96% vs 15.87%) and embryo implantation rate (32.26% vs 9.67%) were all significantly higher in the BET group than in the CET group (all P < 0.01). We conclude that in the women aged 38 years or over, the choice of endometrial preparation protocols may depend on the individual specific conditions because the endometrial preparation protocols do not affect FET outcome, but BET can obtain better FET outcomes as compared with CET. Abbreviations: AMA: advanced maternal age; FET: frozen-thawed embryo transfer; NC: natural cycle; COS: controlled ovarian stimulation; HRT: hormone replacement therapy; CET: cleavage-stage embryo transfer; BET: blastocyst-stage embryo transfer; LH: luteinizing hormone; HCG: human chorionic gonadotropin; HMG: human menopausal gonadotropin; FSH: follicle-stimulating hormone; BMI: body mass index.

Frequency of IL-10-producing regulatory B cells associated with disease activity in thyroid-associated orbitopathy.

AIM: To investigate the association between IL-10-producing regulatory B (B10) cells and the clinical features of thyroid-associated orbitopathy (TAO). METHODS: A total of 30 patients with TAO were recruited at Zhongshan Ophthalmic Center from May 2015 to December 2015. Peripheral blood mononuclear cells (PBMCs) were separated from blood samples of 30 TAO patients and 16 healthy controls and stimulated with CD40 ligand and CpG for 48h. The frequency of IL-10+ B cells was examined by flow cytometry and the correlation between the frequency of IL-10+ B cells and clinical features of TAO was analyzed by SPSS. RESULTS: The frequency of IL-10+ B cells among CD19+ B cells in TAO patients was significantly lower than in healthy controls (TAO: 4.66%±1.88% vs healthy control: 6.82%±2.40%, P<0.01). The frequency of IL-10+ B cells showed a positive correlation with disease activity of TAO measured by Clinical Activity Score (CAS) (r=0.50, P<0.01), and became higher in TAO patients with family history of Graves' disease (GD) (P=0.04). CONCLUSION: The decrease of the frequency of IL-10+ B cells in TAO patients indicates the deficiency of B10 cells in TAO, and the positive association with disease activity suggests its important role in TAO inflammation regulation.

[A comparison between clinical value of the liver transplantation standard mathematical model score and Child-Turcotte-Pugh score in evaluating the prognosis of liver failure].

OBJECTIVE: To compare the clinical value of the liver transplantation standard (LTS) mathematical model score and Child-Turcotte-Pugh (CTP) score in evaluating the prognosis of liver failure. METHODS: The clinical data of 150 liver failure patients were analyzed retrospectively. All the patients who were admitted from January 2004 to December 2008 were divided into survival group (n=48) and death group (n=102) in regard to their 90-day survival after their admission. LTS score and CTP score were calculated according to their respective clinical data within 24 hours after their admission. Comparison between LTS score and CTP score was conducted respectively between the survival group and death group. The correlation between LTS score/CTP score and the prognosis of liver failure was made by Spearman rank correlation. The ability of LTS score and CTP score to predict the outcome of liver failure was compared with the receiver operating characteristic (ROC) curve. RESULTS: The LTS score and CTP score of survival group were 38.88+/-4.27 and 11.25+/-0.97, respectively, which were lower than those of death group (52.63+/-10.65 and 12.18+/-1.22, both P<0.01). The correlation coefficient of LTS score and the prognosis of liver failure (r(s)=0.651, P<0.01) was higher than that of CTP score (r(s)=0.366, P<0.01). The area under ROC curve (AUC) of LTS score was 0.897, sensitivity (SN) was 76.52%, specificity (SP) was 91.18%, positive predictive value (PV+) was 94.39%, negative predictive value (PV-) was 66.67%, and Youden index was 0.677, respectively. The AUC of CTP score was 0.716, those of SN, SP, PV+, PV- and Youden index were 40.91%, 92.65%, 91.53%, 44.68% and 0.336, respectively. CONCLUSION: The LTS score is better than the CTP score in evaluating the prognosis of liver failure.