Comparison of Four Lymph Node Stage Methods for Predicting the Prognosis of Distal Cholangiocarcinoma Patients After Surgery

BackgroundThe metastatic status of regional lymph nodes is an effective risk factor for the prognosis of distal cholangiocarcinoma (dCCA). But existing lymph node staging is not accurate enough and is susceptible to interference. This study aims to explore the predictive ability of the log odds of positive lymph nodes (LODDS) staging system of dCCA compared with existing lymph node staging systems.MethodsA total of 928 dCCA patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort, and 207 dCCA patients from West China Hospital who underwent surgery were reviewed as the validation cohort. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were conducted to identify the most meaningful factors relevant to prognosis. The performance of four lymph node stage systems was compared by a model-based approach.ResultAge at diagnosis, pathological grade, American Joint Committee on Cancer (AJCC) tumor 7th T stage, tumor size, radiotherapy, chemotherapy, and lymph node stage system were independent prognostic factors. The model with the LODDS system had a better model fit with the highest C-index (0.679) and 1-/3-/5- area under the receiver operating characteristic curve (AUC) (0.739/0.671/0.658) as well as the lowest Akaike information criterion (AIC) (5,020.52). External validation results from 207 dCCA patients showed a C-index of 0.647 and 1-/3-/5-AUC of 0.740/0.683/0.589. Compared with the lymph node ratio (LNR), AJCC 8th N system, and 7th N system, the 5-year net reclassification improvement (NRI) of the LODDS system was 0.030 (95% CI: −0.079 to 0.147), 0.042 (95% CI: −0.062 to 0.139), and 0.040 (95% CI: −0.057 to 0.146), respectively. The integrated discrimination improvement (IDI) of LODDS improved compared with the LNR model (0.016; 95% CI: −0.001 to 0.036), AJCC 8th N system (0.020; 95% CI: 0.003–0.037), and AJCC 7th N system (0.019; 95% CI: 0.002–0.036). Decision curve analysis (DCA) also shows a greater net benefit of LODDS. In lymph node-negative patients, LODDS reveals a positive linear relationship with the hazard ratio (HR). The stage capacity of LODDS in a subgroup analysis stratified by examined lymph node number (ELNN) was consistent.ConclusionsThe LODDS lymph node stage system has superior predictive performance as compared with the LNR, AJCC 7th, and 8th lymph node stage systems. Meanwhile, LODDS has a more detailed staging ability and good stability.

HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes. Accumulating evidence suggests that dysregulation of m6A modification significantly correlates with tumorigenesis and progression. In this study, we observed an increased expression and positive correlations of all 25 m6A regulators in esophageal cancer (ESCA) data obtained from the TCGA database. Through expression profiling of these regulators, a prognostic score model containing HNRNPA2B1, ALKBH5, and HNRNPG was established, and the high-risk subgroup exhibited strong positive correlations with ESCA progression and outcome. The risk score obtained from this model may represent an independent predictor of ESCA prognosis. Notably, the gene most frequently associated with increased risk was HNRNPA2B1; in ESCA, the increased expression of this gene alone predicted poor prognosis by affecting tumor-promoting signaling pathways through miR-17-92 cluster. An experimental study demonstrated that elevated HNRNPA2B1 expression was positively associated with distant metastasis and lymph node stage, and predicted the poor outcomes of ESCA patients. Knockdown of HNRNPA2B1 significantly decreased the expression of miR-17, miR-18a, miR-20a, miR-93, and miR-106b and inhibited the proliferation of ESCA cells. Therefore, our study indicated that the dynamic changes in 25 m6A regulators were associated with the clinical features and prognosis of patients with ESCA. Importantly, HNRNPA2B1 alone may affect the prognosis of patients with ESCA by regulating the miR-17-92 cluster.

Prognostic value of the miRNA-27a and PPAR/RXRα signaling axis in patients with thyroid carcinoma

The authors aimed to evaluate the prognostic value of miRNA-27a (miR-27a), peroxisome proliferator-activated receptor alpha/gamma ( PPARα/γ) and retinoid X receptor alpha (RXRα) tissue expression in patients with thyroid carcinoma. The expression levels were quantified in 174 archived thyroid specimens using real-time quantitative PCR. Downregulation of miR-27a was associated with lymph node stage and multifocality. PPARα expression was associated with histopathological type, tumor size and lymph node invasion. Moreover, RXRα expression was lower in patients who underwent total/subtotal thyroidectomy or received radioactive iodine treatment. Patients with upregulated miR-27a and downregulated RXRα showed a higher frequency of advanced lymph node stage and relapse by cluster analysis. Both miR-27a and PPARα/RXRα showed association with different poor prognostic indices in thyroid cancer patients.

Prognostic Evaluation for Patients over 45 Years Old with Gallbladder Adenocarcinoma Resection: A SEER-Based Nomogram Analysis

Gallbladder adenocarcinoma is the main histopathological type of gallbladder cancer (GBC), so it is particularly important to understand its biological characteristics. Due to the low incidence of this type of cancer, there are few studies with large sample sizes. The log of positive lymph nodes (LODDS) has been evaluated by many scholars as a lymph node stage that may play a better role than the 8th edition of the American Joint Committee on Cancer (AJCC) lymph node staging system in many cancers. However, the effect of LODDS has not been proven in gallbladder adenocarcinoma. Our research aimed to identify independent prognostic factors that are closely related to overall survival (OS) in patients with gallbladder adenocarcinoma over 45 years of age using data from the Surveillance, Epidemiology and, End Results (SEER) database. All patients were randomly divided into a modeling cohort and an internal validation cohort. Seven independent prognostic factors associated with OS—age, marital status, grade, tumor size, AJCC 8th edition T stage and M stage, and LODDS—were used to build a nomogram to predict 1-, 3-, and 5-year survival. The C-index of our nomogram was 0.735 (95% CI, 0.716 to 0.754), and together with the calibration curve and ROC curve validation, the results confirmed the prediction effect of our nomogram. We believe that our nomogram will be an accurate and convenient method for patient prognosis assessment in the future.

Integrated characterisation of cancer genes identifies key molecular biomarkers in stomach adenocarcinoma

AimsGastric cancer is one of the leading causes for cancer mortality. Recent studies have defined the landscape of genomic alterations of gastric cancer and their association with clinical outcomes. However, the pathogenesis of gastric cancer has not been completely characterised.MethodsDriver genes were detected by five computational tools, MutSigCV, OncodriveCLUST, OncodriveFM, dendrix and edriver, using mutation data of stomach adenocarcinoma (STAD) from the cancer genome altas database, followed by an integrative investigation.ResultsTTN, TP53, LRP1B, CSMD3, OBSCN, ARID1A, FAT4, FLG, PCLO and CSMD1 were the 10 most frequently mutated genes. PIK3CD, NLRC3, FMNL1, TRAF3IP3 and CR1 were the top five hub genes of the blue coexpression module positively correlated with pathological tumour stage and lymph node stage (p values <0.05 for all cases). Hierarchical clustering analysis of copy number variations of driver genes revealed three subgroups of STAD patients, and cluster 2 tumours were significantly associated with lower lymph node stage, less number of positive lymph nodes and higher microsatellite instability and better overall survival than cluster 1 and cluster 3 tumours (p values <0.05 for all cases, Wilcoxon rank-sum test or log rank test). High expression in one or more of DNER, LHCGR, NLRP14, OR4N2, PSG6, TTC29 and ZNF568 genes was associated with increased mortality (p values <0.05 for all cases, log rank test).ConclusionsThe driver genes shed insights into the tumourigenesis of gastric cancer and the genes DNER, LHCGR, NLRP14, OR4N2, PSG6, TTC29 and ZNF568 pave the way for developing prognostic biomarkers for the disease.

The relationship between tumor budding and survival in colorectal carcinomas

SUMMARY OBJECTIVE Tumor budding is a parameter that is increasingly understood in colorectal carcinomas. We aimed to investigate the relationship between tumor budding, prognostic factors, and survival METHODS A total of 185 patients who had undergone colorectal surgery were observed. Tumor budding, the tumor budding score, and the relationship between these and prognostic factors, and survival investigated. RESULTS Tumor budding was found in 91 (49.2%) cases. The relationship between the tumor budding score and histological grade, lymphovascular invasion, perineural invasion, pathological lymph node stage, and mortality rates were significant. CONCLUSION In our study, the relationship between tumor budding and survival is very strong. Considering these findings and the literature, the prognostic significance of tumor budding becomes clear and should be stated in pathology reports.

Correlation of axillary lymph nodes involvement and Nottingham prognostic index with various histopathologic prognostic factors in invasive breast carcinoma

Background: Breast cancer is the commonest cancer of urban Indian women and the second commonest in the rural women. The clinical management of this tumor relies on various prognostic factors, most importantly lymph node stage, tumor size and histologic grade. There have been attempts at integration of these factors into meaningful indices. The most widely used of these is the Nottingham prognostic index (NPI), this study was aimed to evaluate the NPI in a group of breast cancer patients and to correlate NPI with other clinical and histo-morphological features.Methods: This was a two-year prospective, observational study was done in the Department of Surgery, Tertiary Care Teaching Hospital of Maharashtra, India. A total of 50 patients who presented with invasive carcinoma of breast from October 2016 to October 2018 were enrolled.Results: Most of the patients belonged to the age group of 41 to 50 years (34%) and the mean age of patients in study was 51.18±11.93 years. Left breast was more affected (62%) than the right breast (38%). Majority of the cases had tumor size of <5 cm (70%) and the mean size of was 4.65±1.89 cms. Majority of the patients (62%) belonged to Bloom Richardson (BR) Grade II and 24% of the patients were ER and PR positive. Lymphovascular invasion was present in 74% of the patients. There was significant positive correlation between tumor size and lymph node involvement. Significant correlation was noted between NPI score and tumor size, positive lymph nodes and BR grade. The mean NPI scores in patients with lymphovascular invasion were noted as 4.92±1.05, compared to 4.83±0.93 among the patients in whom lymphovascular invasion was absent (p=0.779). The mean NPI scores in patients with ER-, PR- were slightly high (4.91±0.94) compared to ER+, PR+ patients (4.76±1.19) (p=0.778).Conclusions: NPI is an essential and valuable prognostic indicator, which should be incorporated in breast cancer reporting by the histopathologists and also primary tumor size, lymph node stage and histological grade which provides further guideline to treating clinicians to choose treatment modalities for the patient and in deciding to follow up plan as well.