ABSTRACT
Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1â¶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.
ABSTRACT
Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Laparoscopy , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/pathology , CA-19-9 Antigen , Cholangiocarcinoma/diagnosis , Female , Humans , Lymphatic Metastasis , Male , Nomograms , Prognosis , Retrospective StudiesABSTRACT
OBJECTIVE: The present study aimed to determine the expression, roles and functional mechanisms of long non-coding RNA AFAP1-AS1 (AFAP1-AS1) in the progression of ovarian cancer. PATIENTS AND METHODS: AFAP1-AS1 expression was assessed in ovarian cancer samples and ovarian cancer cell lines by quantitative real-time PCR. The association of AFAP1-AS1 expression with clinicopathological factors was also analyzed. Gain-/loss-of-function studies were performed to investigate the expression pattern and functional role of AFAP1-AS1 in ovarian cancer. Effects of AFAP1-AS1 on cell proliferation were studied using cell-counting kit-8 assay. The effect of AFAP1-AS1 on ovarian cancer cells apoptosis was assessed by flow cytometry assay. RESULTS: AFAP1-AS1 was highly expressed both in ovarian cancer samples and cell lines compared with their corresponding normal counterparts. High AFAP1-AS1 expression was significantly associated with response and FIGO stage. Gain-of-function and loss-of-function experiments showed that AFAP1-AS1 promoted ovarian cancer cells proliferation. Flow cytometry assay showed that knockdown of AFAP1-AS1 promoted ovarian cancer cells apoptosis. CONCLUSIONS: Our results suggested that AFAP1-AS1 might be considered as a novel oncogene involved in ovarian cancer progression.
Subject(s)
Gene Expression Regulation, Neoplastic , Ovarian Neoplasms/genetics , RNA, Long Noncoding/genetics , Apoptosis , Cell Line, Tumor , Cell Proliferation , Female , Humans , Oncogenes , Real-Time Polymerase Chain ReactionABSTRACT
The risk factors of low birth weight infant (LBW) were prospectively studied in 26,941 pregnant women. Investigations included sociodemographic risks, environmental behavioural conditions, medical diseases before pregnancy and current pregnancy complications. The adjusted odds ratios for various risk factors were calculated from multiple logistic regression model. In this analysis, placenta abnormalities uterine malformations and pregnancy-induced hypertension were shown to be the main risk factors. Preterm delivery occurred more frequently in women with diabetes and injuries in the third trimester. Term SGA babies were usually seen in women who had inadequate diet during pregnancy or in women with maternal heart disease. The risk factors of maternal age, educational background, parental smoking etc were less important than maternal diseases or pregnancy complications. The present study indicated prenatal care, started early with regular check-ups was mast important in preventing prematurity and LBW infant in China.