Independent Predictor Of Distant Metastasis Research Articles

A nomogram model for predicting distant metastasis of newly diagnosed colorectal cancer based on clinical features.

Colorectal cancer is one of the most common primary malignancies and the third most common cause of cancer death in both men and women in the United States. Among people diagnosed with initial colorectal cancer, 22% had metastatic colorectal cancer, while the 5-year survival rate was less than 20%. The purpose of this study is to develop a nomogram for predicting distant metastasis in newly diagnosed colorectal cancer patients and to identify high-risk groups. We retrospectively reviewed the data of patients who were diagnosed with colorectal cancer at Zhong nan Hospital of Wuhan University and People's Hospital of Gansu Province between January 2016 and December 2021. Risk predictors for distant metastasis from colorectal patients were determined by the univariate and multivariate logistic regression analyses. Nomograms were developed to predict the probabilities of distant metastatic sites of colorectal cancer patients and evaluated by calibration curves, receiver operating characteristic curves, and decision curve analysis (DCA). A total of 327 cases were included in this study: 224 colorectal cancer patients from Zhong nan Hospital of Wuhan University were incorporated into the training set, and 103 colorectal cancer patients from Gansu Provincial People's Hospital were incorporated into the testing set. By univariate logistic regression analysis, platelet (PLT) level (p = 0.009), carcinoembryonic antigen (CEA) level (p = 0.032), histological grade (p < 0.001), colorectal cancer tumor markers (p < 0.001), N stage (p < 0.001), and tumor site (p = 0.005) were associated with distant metastasis in colorectal cancer patients. Multivariate logistic regression analysis showed that N stage (p < 0.001), histological grade (p = 0.026), and colorectal cancer markers (p < 0.001) were independent predictors of distant metastasis in patients initially diagnosed with colorectal cancer. The above six risk factors were used to predict distant metastasis of newly diagnosed colorectal cancer. The C-indexes for the prediction of the nomogram were 0.902 (95% confidence interval (CI), 0.857-0.948). The nomogram showed excellent accuracy in predicting distant metastatic sites, and clinical utility may facilitate clinical decision-making.

Predictive factors of distant metastasis in surgically treated HPV-positive tonsil cancer.

Human papilloma virus (HPV)-related tonsil cancer is associated with favorable outcomes. The purpose of this study was to define factors affecting distant metastasis in patients with surgically treated HPV-positive tonsil cancer. The present study enrolled 76 patients diagnosed with HPV-positive tonsil cancer who underwent primary surgery between January 2010 and December 2021. Twelve (15.7%) patients experienced a distant failure with a median follow-up time of 43 months. Sites of distant metastasis included the lung (n = 10), liver (n = 1), and brain (n = 1). Upon multivariate analysis, an advanced T stage (odds ratio [OR]: 13.94, 95% confidence interval [CI]: 1.29-149.863, p = 0.003) and margin involvement (OR: 5.96, 95% CI: 1.33-26.76, p = 0.02) were independent predictors of distant metastases. The five-year disease-specific survival for the entire cohort was 85%. The multivariate analysis confirmed that distant metastasis (hazard ratio [HR]: 12.688, 95% CI: 3.424-47.016; p < 0.001) and margin involvement (HR: 6.243; 95% CI: 1.681-23.191; p = 0.006) were significant factors associated with the five-year disease-specific survival. HPV-positive tonsil cancer patients with an advanced T stage and a positive surgical margin have a substantial risk of distant metastases. Distant metastasis and margin involvement are factors that affect their survival.

Pretreatment risk prediction for distant metastasis in locally advanced rectal cancer.

248 Background: Distant metastasis is the most common form of recurrence in locally advanced rectal cancer. This study aimed to identify pretreatment risk factors for distant metastases in patients with locally advanced rectal cancer. Methods: This single-institution retrospective study included 285 patients who underwent preoperative chemoradiotherapy followed by surgical resection between January 2016 and December 2020. Pretreatment clinical characteristics, MRI findings, and blood profiles were analyzed to investigate its association with distant metastasis. Results: With a median follow-up of 39 months (range: 6 - 78), 42 patients had confirmed distant metastasis (14.7%), and most distant metastasis occurred within three years (40 patients, 95.2%). In the multivariate analysis, pretreatment extramural venous invasion (EMVI, HR = 3.05, p &lt; 0.001) and carcinoembryonic antigen (CEA) &gt; 10 ng/mL (HR = 2.77, p = 0.002) were independent predictors of distant metastasis. Patients with no adverse factors had significantly better distant metastasis-free survival than patients with 1 or 2 adverse features (92% vs. 70% vs. 59% (p &lt; 0.001) at 3 years). Conclusions: Pretreatment CEA and EMVI have predictive significance for distant metastasis in locally advanced rectal cancer. Our findings may help select patients who may benefit from intensified preoperative treatment, such as total neoadjuvant therapy.

High proportion of circulating CD8 + CD28- senescent T cells is an independent predictor of distant metastasis in nasopharyngeal carcinoma after radiotherapy

BackgroundNasopharyngeal carcinoma (NPC) is a kind of epithelial carcinoma that is common in East and Southeast Asia. Distant metastasis after radiotherapy remains the main cause of treatment failure and preradiotherapy immune system function can influence prognosis. Our study aimed to identify immune-related prognostic factors for NPC after radiotherapy and establish a prognostic model to predict progression-free survival (PFS) and distant metastasis-free survival (DMFS).MethodsWe enrolled NPC patients and divided them into training and validation cohorts with follow-up. We collected clinical information and investigated immune cells, EBV DNA and cytokines in the peripheral blood of NPC patients before radiotherapy and EBV DNA after radiotherapy. Among these immune cells, we included CD8+CD28− T cells, which are a unique T-cell immunosenescent subset that increases in human peripheral blood with increasing age and declining immune function. Based on the detection results and clinical information, we utilized Cox regression and least absolute shrinkage and selection operator (LASSO) regression to screen the PFS and DMFS prognostic factors and build nomograms to predict the PFS and DMFS of NPC. We also verified the results in the validation set.ResultsThree factors associated with PFS were selected: proportion of CD8+CD28− T cells posttreatment EBV and N stage. Three factors associated with DMFS were screened: proportion of CD8+CD28− T cells, posttreatment EBV and N stage. CD8+CD28− T cells are correlated with systemic inflammation and posttreatment immunosuppression. The C-indexes were 0.735 and 0.745 in the training and validation cohorts for predicting PFS. For DMFS, the C-indexes were 0.793 and 0.774 in the training and validation cohorts.ConclusionsThe pretreatment proportion of CD8+CD28− T cells is a candidate prognostic biomarker for NPC after radiotherapy. The constructed nomogram models based on CD8+CD28− T cells have good predictive value.

Cytogenetic Abnormalities for Predicting the Risk of Metastases in Choroidal and Ciliary Body Melanoma.

Choroidal melanoma (CM) and ciliary body melanoma (CBM) are the two most common subtypes of uveal melanoma. Starting from the observation that CBM tends to have a higher metastatic potential than CM, we hypothesized that specific cytogenetic abnormalities could be associated with tumor location - reflecting distinct genetic signatures that would drive the risk of distant spread. Chromosomal alterations were investigated by molecular cytogenetic techniques in 217 and 97 patients with CM and CBM, respectively. Cox proportional hazards regression analysis was used to identify the independent predictors of distant metastasis. Patients with CBM had larger tumor sizes (P < 0.001), higher disease stages (P < 0.001), and more frequently showed distant metastasis (P = 0.002) than those with CM. On analyzing the entire study cohort, we found that specific chromosomal alterations - including chromosome 8p loss (P < 0.001), 1p loss (P < 0.001), and monosomy 3 (P < 0.005) - were independent predictors of distant metastasis. Based on a decision-tree learning algorithm, we identified three specific subgroups of patients with uveal melanoma at high risk of distant spread. Monosomy 3 occurred significantly more frequently in patients with T3 CBM tumors. Specific cytogenetic abnormalities - including chromosome 8p loss, 1p loss, and monosomy 3 - are independent risk factors for distant metastasis in uveal melanoma. Larger tumor size at presentation and monosomy 3 contribute to a higher metastatic risk in patients with CBM.

Prediction of distant metastasis in esophageal cancer using a radiomics–clinical model

BackgroundDistant metastasis, which occurs at a rate of 25% in patients with esophageal cancer (EC), has a poor prognosis, with previous studies reporting an overall survival of only 3–10 months. However, few studies have been conducted to predict distant metastasis in EC, owing to a dearth of reliable biomarkers. The purpose of this study was to develop and validate an accurate model for predicting distant metastasis in patients with EC.MethodsA total of 299 EC patients were enrolled and randomly assigned to a training cohort (n = 207) and a validation cohort (n = 92). Logistic univariate and multivariate regression analyses were used to identify clinical independent predictors and create a clinical nomogram. Radiomic features were extracted from contrast-enhanced computed tomography (CT) images taken prior to treatment, and least absolute shrinkage and selection operator (Lasso) regression was used to screen the associated features, which were then used to develop a radiomic signature. Based on the screened features, four machine learning algorithms were used to build radiomics models. The joint nomogram with radiomic signature and clinically independent risk factors was developed using the logical regression algorithm. All models were validated and compared by discrimination, calibration, reclassification, and clinical benefit.ResultsMultivariable analyses revealed that age, N stage, and degree of pathological differentiation were independent predictors of distant metastasis, and a clinical nomogram incorporating these factors was established. A radiomic signature was developed by a set of sixteen features chosen from 851 radiomic features. The joint nomogram incorporating clinical factors and radiomic signature performed better [AUC(95% CI) 0.827(0.742–0.912)] than the clinical nomogram [AUC(95% CI) 0.731(0.626–0.836)] and radiomics predictive models [AUC(95% CI) 0.754(0.652–0.855), LR algorithms]. Calibration and decision curve analyses revealed that the radiomics–clinical nomogram outperformed the other models. In comparison with the clinical nomogram, the joint nomogram's NRI was 0.114 (95% CI 0.075–0.345), and its IDI was 0.071 (95% CI 0.030–0.112), P = 0.001.ConclusionsWe developed and validated the first radiomics–clinical nomogram for distant metastasis in EC which may aid clinicians in identifying patients at high risk of distant metastasis.

Establishment and Validation of a Novel Nomogram for Predicting Distant Metastasis in Patients with Invasive Lung Adenocarcinoma.

To establish and verify a nomogram for predicting distant metastasis in invasive lung adenocarcinoma (IAC). Observational study. Department of Thoracic Surgery, Jinan Central Hospital, Jinan, China, from December 2021 to May 2022. To create a nomogram, univariate and multivariate logistic regression analyses wereused to identify the independent predictors of distant metastasis. The calibration, discrimination, and clinical performance of the nomogram were tested by calibration plots, area under receiver operating characteristic curve (AUC), and decision curve analysis (DCA). Age at diagnosis (<70 years), histological type (invasive mucinous adenocarcinoma), T stage, N stage, surgical approach, and lymph node dissection were independent predictors for the development of nomogram. Compared with the American Joint Committee on Cancer-8th edition staging system, AUC showed that this prediction model has a higher predictive performance (training set: 0.922 vs. 0.790; verification set: 0.919 vs. 0.779). In addition, the overall survival time (OS) of IAC patients was meaningfully different among the three groups of different risks stratified based on model score (p <0.001). The prediction model constructed according to factors such as histological type and surgical approach in this study can accurately predict distant metastasis in IAC patients and define high-risk patients according to nomogram score. Invasive adenocarcinoma IAC, Distant metastasis, Nomogram, Surveillance, Epidemiology and end results SEER.

Abstract 5280: TERT promoter mutations are an independent predictor of distant metastasis in Middle Eastern papillary thyroid microcarcinoma

Abstract Background: Papillary thyroid microcarcinomas (PTMCs) have been attributed to the recent increased incidence of thyroid cancer. Although indolent, a subset of PTMC could potentially develop distant metastasis (DM). This study aimed to evaluate the clinico-pathological features and molecular characteristics of PTMC and identify the risk factors for DM in PTMC patients from Middle Eastern ethnicity. Methods: We retrospectively analyzed 210 patients with histologically confirmed PTMC. Clinico-pathological associations for DM, BRAF mutation and TERT mutation were analyzed successfully in 184 patients. Multivariate analysis was performed using Cox proportional hazards model and logistic regression analysis. Results: Among the PTMC patients included in this cohort, DM was noted in 6.0%(11/184), whereas tumor relapse occurred in 29/184 (15.8%). Of the 11 cases with DM, lung metastasis occurred in 8 cases, bone metastasis in 2 cases and brain metastasis in 1 case. Presence of extrathyroidal extension and older age were significantly associated with DM. Molecular analysis showed BRAF V600E mutations to be the most frequent, being detected in 45.7% (84/184). TERT promoter mutations were detected in 16 (8.7%) cases and were significantly associated with DM and shorter metastasis-free survival in multivariate analysis. Conclusions: Our study indicates a surprisingly high frequency of TERT promoter mutation in Saudi patients with PTMC. Identifying TERT promoter mutations as an independent predictor of DM in patients with microcarcinoma could explain the inherent aggressive nature of PTMC from Middle Eastern ethnicity and magnify its role in patient risk stratification, which might help in improving therapeutic strategy for these patients. Citation Format: Saeeda Omer Ahmed, Abdul K. Siraj, Sandeep K. Parvathareddy, Kaleem Iqbal, Zeeshan Qadri, Maha Al-Rasheed, Sarah Siraj, Saravanan Thangavel, Roxanne Diaz, Allianah Benito, Ingrid F. Victoria, Khawla S. AlKuraya. TERT promoter mutations are an independent predictor of distant metastasis in Middle Eastern papillary thyroid microcarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5280.

TERT Promoter Mutations Are an Independent Predictor of Distant Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma.

BackgroundPapillary thyroid microcarcinomas (PTMCs) have been attributed to the recent increased incidence of thyroid cancer. Although indolent, a subset of PTMC could potentially develop distant metastasis (DM). This study aimed to evaluate the clinico-pathological features and molecular characteristics of PTMC and identify the risk factors for DM in PTMC patients from Middle Eastern ethnicity.MethodsWe retrospectively analyzed 210 patients with histologically confirmed PTMC. Clinico-pathological associations for DM, BRAF mutation and TERT mutation were analyzed successfully in 184 patients. Multivariate analysis was performed using Cox proportional hazards model and logistic regression analysis.ResultsAmong the PTMC patients included in this cohort, DM was noted in 6.0% (11/184), whereas tumor relapse occurred in 29/184 (15.8%). Of the 11 cases with DM, lung metastasis occurred in 8 cases, bone metastasis in 2 cases and brain metastasis in 1 case. Presence of extrathyroidal extension and male sex were significantly associated with DM. Molecular analysis showed BRAF V600E mutations to be the most frequent, being detected in 45.7% (84/184). TERT promoter mutations were detected in 16 (8.7%) cases and were significantly associated with DM and shorter metastasis-free survival in multivariate analysis.ConclusionsOur study indicates a surprisingly high frequency of TERT promoter mutation in Saudi patients with PTMC. Identifying TERT promoter mutations as an independent predictor of DM in patients with microcarcinoma could explain the inherent aggressive nature of PTMC from Middle Eastern ethnicity and magnify its role in patient risk stratification, which might help in improving therapeutic strategy for these patients.

Predicting Distant Metastasis in Young-Onset Colorectal Cancer After Surgery: A Retrospective Study.

BackgroundAlthough overall colorectal cancer (CRC) cases have been declining worldwide, there has been an increase in the incidence of the CRC among individuals younger than 50 years old, which is associated with distant metastasis (DM) and poor prognosis.MethodsYoung-onset CRC patients’ postoperative data were collected from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. Data from the SEER database were divided into early stage and advanced stage according to whether chemoradiotherapy was recommended in the guidelines. Independent risk factors for DM were explored by using univariate and multivariate logistic regression separately. A predictive model was established and presented as nomogram in the training set of advanced stage. The model was internally verified in testing set and externally validated in a cohort of 145 patients from Zhongnan Hospital of Wuhan University. The accuracy, reliability, and clinical application value were assessed using the receiver operating characteristic curve (ROC), the area under the curve (AUC), calibration curve, and decision curve analysis (DCA), respectively. Different risk subgroups of DM were classified according to the scores of the nomogram in the training set of advanced stage.ResultsA total of 5,584 patients were eligible and enrolled in our study in which 1,277 were in early stage and 4,307 in advanced stage. Preoperative CEA positive was found to be an independent predictor of DM in early stage. Multivariate logistic regression analysis showed that tumor size, degree of differentiation, T stage, N stage, preoperative CEA, and whether radiation or chemotherapy performed were independent risk factors for DM (all, p < 0.05) in advanced stage. Great accuracies were achieved in our nomogram with AUC of 0.801 in training set, 0.811 in testing set, and 0.791 in the validation cohort, respectively. Calibration curves and DCA in internal validation and external validation both showed good stability and clinical utility values.ConclusionsPreoperative CEA positive was a significant predictor of DM for young-onset CRC patients. A novel nomogram containing clinical and pathological features was established for predicting DM of advanced CRC in patients younger than 50 years old. This tool may serve as an early alert for clinicians to DM and make better clinical treatment regimens.

MRI-detected extramural vascular invasion (mrEMVI) as the best predictive factor to identify candidates to total neoadjuvant therapy in locally advanced rectal cancer.

Chemotherapy in locally advanced rectal cancer (LARC) is shifting from an adjuvant setting to a total neoadjuvant therapy (TNT) strategy, that relies on distant metastases (DM) risk prediction. This study aims to assess the accuracy of magnetic resonance imaging-detected extramural vascular invasion (mrEMVI) as predictive factor for DM in LARC, compared with other MRI-detected and pathologic factors. This retrospective single-center study analyzed data extracted from a series of consecutive patients curatively resected for rectal cancer at Mauriziano Hospital in Turin (Italy) from January 2013 to December 2018. Data from 69 patients were analyzed. MrEMVI was detected in 31 (44.9%) cases. Median follow-up was 39.9 months. DM and local recurrence occurred in 19 (27.5%) and 4 (5.8%) patients. One- and 3-year cumulative incidence of DM were 32.3% (95% confidence interval [CI]: 0.17-0.49) and 56.8% (95% CI: 0.35-0.74) in the mrEMVI-positive group and 5.4% (95% CI: 0.01-0.16) and 14.0% (95% CI: 0.05-0.27) in the mrEMVI-negative group (log-rank test, p < 0.001). In the multivariate analysis of MRI factors, mrEMVI was the only independent predictor of DM (HR: 3.59, CI: 1.21-10.69, p = 0.02). This study confirmed that mrEMVI is a powerful predictor of DM in LARC. It should be routinely reported and considered during multidisciplinary care strategy planning.

Hyaluronic Acid Correlates With Bone Metastasis and Predicts Poor Prognosis in Small-Cell Lung Cancer Patients.

BackgroundHyaluronan (HA) is one of the essential elements of the extracellular matrix (ECM), involved in the onset of metastasis in various tumors. The interaction and binding of the ligand–receptor HA/cluster of differentiation-44 (CD44) regulate the physical and biochemical properties of the ECM, which correlates with an increased propensity toward metastasis and poor survival outcome. Our study aimed to explore HA for predicting metastasis and survival rate in patients with small-cell lung cancer (SCLC).Materials and MethodsThis prospective cohort study recruited 72 patients with SCLC. Plasma HA and CD44 levels were assayed by enzyme-linked immunosorbent assay (ELISA) for 72 cases before initial systematic treatment (baseline samples), and plasma HA was detected via after-2-cycle-chemotherapy (A-2-C-CT) in 48 samples. Logistic regression analysis and the Cox proportional risk model were used to determine the independent predictors of distant metastasis and survival rate of patients.ResultsBaseline plasma HA was notably associated with bone metastasis (BM) [OR (95% CI = 1.015 (1.006–1.024), p = 0.001]. Multivariate logistic regression analysis showed that baseline plasma HA was chosen as an independent predictor of BM. Either baseline HA or CD44 or both were associated with BM. Dynamic alteration of HA was notably associated with A-2-C-CT clinical efficacy. Multivariate Cox regression analysis in forward likelihood ratio showed that A-2-C-CT HA was an independent predictor of progression-free survival (PFS) and overall survival (OS).ConclusionsHA appears to be used as an independent predictive factor for BM, and the dynamic detection of HA can predict prognosis in SCLC patients. The mechanism of the HA/CD44 axis in BM of SCLC deserves further exploration.

The Impact of the Percent of Residual Prostate-Specific Antigen on Metastasis-Free Survival in Patients with Persistent Prostate-Specific Antigen after Radical Prostatectomy.

Persistent levels of prostate-specific antigen (PSA) is a poor prognostic factor for recurrence after radical prostatectomy (RP). We investigated the impact of the percentage of residual PSA (%rPSA) [(post-/preoperative PSA)×100], representing a biochemical residual tumor, and the first postoperative PSA (fPSA) level on metastasis-free survival (MFS) in men with persistent levels of PSA after RP. We retrospectively identified male patients within a single tertiary referral hospital database who harbored persistent (≥0.1 ng/mL) vs. undetectable (<0.1 ng/mL) PSA levels 4 to 8 weeks after RP. Kaplan-Meier analyses and Cox regression models were used to test the effect of persistent PSA levels, the fPSA level, and %rPSA on MFS. Of 1,205 patients, 178 patients with persistent PSA levels were enrolled. Seven-year MFS rates were 60.5% vs. 84.3% (p<0.001) for patients with a %rPSA ≥6% and <6%, respectively. Multivariable Cox regression models of the overall cohort revealed that persistent PSA levels (hazard ratio [HR], 3.94; p=0.010), extracapsular extension (HR, 4.17; 95% confidence interval [CI], 1.06-16.41; p=0.041), and pathological Gleason grade group (pGGG) (HR, 3.69; 95% CI, 1.32-10.27; p=0.013) were independent predictors of metastasis. Multivariable Cox regression models in men with persistent PSA levels revealed that the %rPSA (HR, 8.92; 95% CI, 1.74-45.71; p=0.009) and pGGG 4-5 (HR, 4.13; 95% CI, 1.22-13.96; p=0.022) were independent predictors of distant metastasis, but not the fPSA level after surgery. Persistent levels of PSA were associated with worse MFS after RP. In men with persistent PSA levels after RP, the %rPSA is a valuable predictor of MFS unlike the fPSA level.

18F-FDG-PET/CT can be used to predict distant metastasis in hypopharyngeal squamous cell carcinoma

BackgroundHypopharyngeal squamous cell carcinoma (HPSCC) has a high rate of distant metastasis, resulting in poor prognosis. The role of the maximum standardized uptake value (SUVmax), which was assessed via pretreatment 18-fluorodeoxyglucose positron emission tomography (FDG-PET), and computed tomography (CT) was examined, for predicting distant metastasis and survival.MethodsThis study included 121 patients who underwent pretreatment FDG-PET/CT scanning and subsequent treatment for HPSCC. The SUVmax was measured via FDG-PET/CT. A receiver operating characteristic (ROC) curve analysis was used to determine whether the SUVmax was a predictor of distant metastasis and to select the best cutoff value. Univariate and multivariate Cox hazard regression analyses were used in identifying associations between the SUVmax and other clinicopathological factors with distant metastasis-free survival.ResultsDistant metastases were identified in 33 patients during the median follow-up of 24 months after treatment. The ROC curve analysis determined that SUVmax was predictive of distant metastasis and identified a SUVmax of 13.9 as the best potential cutoff value. The univariate analysis showed that T and N classification, clinical stage, and SUVmax were significantly related to distant metastasis. However, in multivariate analysis, an SUVmax ≥ 13.9 was the only independent predictor of distant metastasis. Patients with high SUVmax values displayed significantly shorter distant metastasis-free survival and overall survival.ConclusionsSUVmax determined via pretreatment FDG-PET/CT is useful for predicting distant metastasis, distant metastasis-free survival, and overall survival in patients with HPSCC.Graphical

Loss of ZNF677 Expression Is an Independent Predictor for Distant Metastasis in Middle Eastern Papillary Thyroid Carcinoma Patients.

Thyroid cancer incidence has increased in recent decades. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Approximately 30% of PTC patients develop recurrence or distant metastasis and tend to have poor prognosis. Therefore, the identification of targetable biomarkers in this subset of patients is of great importance. Accumulating evidence indicates that zinc finger protein 677 (ZNF677), which belongs to the zinc finger protein family, is an important effector during the progression of multiple malignancies. However, its role in Middle Eastern PTC patients has not been fully illustrated. Here, we uncovered the molecular mechanism and the clinical impact of ZNF677 expression in a large cohort of more than 1200 Middle Eastern PTC and 15 metastatic tissues. We demonstrated that ZNF677 is frequently downregulated in primary PTC (13.6%, 168/1235) and showed that complete loss of expression of ZNF677 is significantly associated with aggressive clinico-pathological markers such as extrathyroidal extension (p = 0.0008) and distant metastases (p < 0.0001). We also found a significantly higher incidence of ZNF677 loss in primary tumors with distant metastases (33.3%; p < 0.0001) as well as in distant metastatic tissues (46.7%; p = 0.0002) compared to the overall cohort (13.6%). More importantly, PTC with loss of ZNF677 expression showed significantly lower metastasis-free survival (p = 0.0090). Interestingly, on multivariate logistic regression analysis, ZNF677 loss was an independent predictor of distant metastasis in PTC (Odds ratio = 2.60, 95% Confidence interval = 1.20–5.62, p = 0.0155). In addition, we found a significant association between ZNF677 loss and phospho-AKT expression (p < 0.0001). Our functional molecular results suggest that ZNF677 acts as a tumor suppressor, mediating its effect by inhibiting AKT phosphorylation. Taken together, our results highlight the pivotal role played by ZNF677 during carcinogenesis and metastasis formation in Middle Eastern PTC patients.

Identification and validation of potential novel biomarkers to predict distant metastasis in differentiated thyroid cancer.

BackgroundDistant metastasis (DM) is not common in differentiated thyroid cancer (DTC). However, it is associated with a significantly poor prognosis. Early detection of high-risk DTC patients is difficult, and the molecular mechanism is still unclear. Therefore, the present study aims to establish a novel predictive model based on clinicopathological parameters and DM-related gene signatures to provide guidelines for clinicians in decision making.MethodsWeighted gene co-expression network analysis (WGCNA) was performed to discover co-expressed gene modules and hub genes associated with DM. Univariate and multivariate analyses were carried out to identify independent clinicopathological risk factors based on The Cancer Genome Atlas (TCGA) database. An integrated nomogram prediction model was established. Finally, real hub genes were validated using the GSE60542 database and various thyroid cell lines.ResultsThe midnightblue module was most significantly positively correlated with DM (R=0.56, P=9e-06) by as per WGCNA. DLX5 (AUC: 0.769), COX6B2 (AUC: 0.764), and LYPD1 (AUC: 0.760) were determined to be the real hub genes that play a crucial role in predicting DM. Meanwhile, univariate and multivariate analyses demonstrated that T-stage (OR, 15.03; 95% CI, 1.75–319.40; and P=0.024), histologic subtype (OR, 0.17; 95% CI, 0.03–0.92; and P=0.042) were the independent predictors of DM. Subsequently, a nomogram model was constructed based on gene signatures and independent clinical risk factors exhibited good performance. Additionally, the mRNA expressions of real hub genes in the GSE60542 dataset were consistent with TCGA.ConclusionsThe present study has provided a reliable model to predict DM in patients with DTC. This model is likely to serve as an individual risk assessment tool in therapeutic decision-making.

Novel imaging classification system of nodal disease in human papillomavirus-mediated oropharyngeal squamous cell carcinoma prognostic of patient outcomes.

Matted nodes in human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPC) is an independent predictor of distant metastases and decreased overall survival. We aimed to classify imaging patterns of metastatic lymphadenopathy, analyze our classification system for reproducibility, and assess its prognostic value. The metastatic lymphadenopathy was classified based on radiological characteristics for 216 patients with HPV-mediated OPC. Patient outcomes were compared and inter-rater reliability was calculated. The presence of ≥3 abutting lymph nodes with imaging features of surrounding extranodal extension (ENE), one subtype of matted nodes, was associated with worse 5-year overall survival, overall recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival (p ≤ 0.03). Other patterns were not significantly associated with outcome measures. Overall inter-rater agreement was substantial (κ = 0.73). One subtype of matted nodes defined by ≥3 abutting lymph nodes with imaging features of surrounding ENE is the radiological marker of worst prognosis.

Comparison of StemPrintER, a novel biology-based genomic predictor of distant recurrence in breast cancer, with Oncotype DX in the TransATAC cohort.

1020 Background: Accurate prediction of distant metastasis (DM) in early stage ER+/HER2- breast cancer (BC) patients is vital to avoid over/under-treatment with adjuvant chemotherapy (CT). The OncotypeDX Recurrence Score (RS) is a widely used tool to assist clinical decision-making for CT. The StemPrintER Risk Score (SPRS) is an alternative genomic predictor based on the biology of cancer stem cells that predicts recurrence risk in ER+/HER2- BCs (Pece S. et al., EBioMedicine 2019). Here, we analyze the prognostic value of SPRS in the TransATAC cohort of post-menopausal ER+/HER2- BC patients, and compare the prognostic information provided by SPRS and RS for 10-year risk of DM. Methods: The likelihood χ2 (LRχ2) and Kaplan-Meier survival analyses were used to assess prognostic information provided by SPRS, RS and the clinical treatment score (CTS) in 818 TransATAC patients treated with anastrozole or tamoxifen for 5 years. Comparative analyses were made for DM risk over the 10-year follow-up, as well as in the early (0-5 years) or late (5-10 years) interval, according to nodal status. Results: Used as a continuous variable, SPRS was an independent predictor of DM in years 0-10 among all patients when adjusted for clinical parameters as expressed by the CTS [HR=1.43 (1.18-1.73), P&lt;0.0001], as well as in node-negative [HR=1.51 (1.17-1.94), P=0.001] but not node-positive (N1-3) patients [HR=1.29 (0.95-1.75), P=0.11]. A predefined SPRS cut-off was used to stratify patients into low vs. high risk groups [LOW: N=454, 10-year DM rate=5.8%; HIGH: N=364, 10-year DM rate=21.9%; HRHIGH vs. LOW=2.96 (1.85-4.73); P&lt;0.0001]. SPRS outperformed RS in providing prognostic information for 10-year DM risk (SPRS: HR=1.79, P&lt;0.0001, LRχ2=33.4; RS: HR=1.52, P&lt;0.0001, LRχ2=22.1), with even greater differences in late DM prediction in N0 patients. SPRS also provided more prognostic information than RS to CTS (ΔLRχ2: SPRS+CTS vs. CTS= 14.9; RS+CTS vs. CTS= 9.7). Conclusions: In ER+/HER2- TransATAC BC patients, SPRS was highly prognostic for DM and was superior to RS in providing additional prognostic information to conventional clinicopathological parameters.

Explication of the roles of prostate health index (PHI) and urokinase plasminogen activator (uPA) as diagnostic and predictor tools for prostate cancer in equivocal PSA range of 4-10ng/mL.

BackgroundProstate cancer (PCa) is one of the most commonly encountered cancers and the leading cause of death worldwide. Currently used biomarkers accounts difficulties in discriminating benign from malignant cases or predicting outcome, so investigating new biomarkers performance is needed.ObjectivesAssessment of diagnostic and predictor roles of prostate health index (PHI) and urokinase plasminogen activator (uPA) in PCa.Methods194 males with initial tPSA of 4–10 ng/mL were categorized into three groups: PCa, benign prostatic hyperplasia (BPH) and healthy control. Serum levels of tPSA, fPSA, p2PSA, and uPA were performed by ELISA with calculation of PHI as (p2PSA/fPSA) × √PSA.ResultsPHI and uPA were significantly higher in PCa patients relevant to BPH and healthy control (p ≤ 0.001). Both markers outperformed all assessed biomarkers and showed the highest area under the curve (AUC) in ROC curve analysis. Both were significantly higher in PCa patients with {Gleason score ≥ 7, late stages (cT2b,c; T3), LN extension and distant metastasis}relative to their counterparts. Additionally, PHI and uPA and were independent predictors of distant metastasis and Gleason score ≥ 7, while PHI was predictor of LN invasion (β = 0.25, p = 0.004).ConclusionPHI and uPA would be of potential value in discriminating between PCa, BPH and healthy men in addition, both are promising as independent predictors of adverse pathological features.

Prognostic significance of TERT promoter and BRAF mutations in TIR-4 and TIR-5 thyroid cytology.

Follicular-derived thyroid cancers generally have a good prognosis, but in a minority of cases, they have an aggressive behavior and develop distant metastases, with an increase in the associated mortality. None of the prognostic markers currently available prior to surgery can identify such cases. TERT promoter and BRAF gene mutations were examined in a series of 436 consecutive TIR-4 and TIR-5 nodes referred for surgery. Follow-up (median: 59 months, range: 7-293 months) was available for 384/423 patients with malignant nodes. TERT promoter and BRAF mutations were detected in 20/436 (4.6%) and 257/434 thyroid nodules (59.2%), respectively. At the end of the follow-up, 318/384 patients (82.8%) had an excellent outcome, 48/384 (12.5%) had indeterminate response or biochemical persistence, 18/384 (4.7%) had a structural persistence or died from thyroid cancer. TERT promoter mutations correlated with older age (P < 0.0001), larger tumor size (P = 0.0002), oxyntic and aggressive PTC variants (P = 0.01), higher tumor stages (P < 0.0001), distant metastases (<0.0001) and disease outcome (P < 0.0001). At multivariate analysis, TERT promoter mutation was not an independent predictor of disease outcome. TERT promoter mutation- (OR: 40.58; 95% CI: 3.06-539.04), and N1b lymph node metastases (OR: 40.16, 95% CI: 3.48-463.04) were independent predictors of distant metastases. BRAF mutation did not predict the outcome, and it correlated with a lower incidence of distant metastases (P = 0.0201). TERT promoter mutation proved an independent predictor of distant metastases, giving clinicians the chance to identify many of the patients who warranted more aggressive initial treatment and closer follow-up.