Advanced American Joint Committee On Cancer Research Articles

Comparison of the clinical features and long-term prognosis of gallbladder neuroendocrine carcinoma versus gallbladder adenocarcinoma: A propensity score-matched analysis.

Gallbladder neuroendocrine carcinoma (GBNEC) is rare and characterized by a low degree of tumor differentiation. The clinical features of GBNEC versus gallbladder adenocarcinoma (GBADC) remain a subject of debate. A total of 201 GBADC and 36 GBNEC cases that underwent surgery resection between January 2010 and 2022 at the Department of Biliary Surgery, West China Hospital, Sichuan University were included. A 1:1 propensity score matching (PSM) was performed based on seven predefined variables: age, sex, the American Joint Committee on Cancer (AJCC) stage, resection status, perineural invasion (PNI), lymphovascular invasion (LVI), and degree of tumor differentiation. Compared with GBADC, GBNEC patients were younger (median age 56.0 vs 64.0 years; P = 0.001), and more patients presented with advanced stages of tumor (P = 0.003). Patients with GBNEC also had a higher rate of PNI (55.6% vs 22.4%; P < 0.001), and LVI (63.9% vs 45.80%; P = 0.658). Before PSM, GBNEC patients had inferior prognoses compared with GBADC patients with a shorter median overall survival (mOS) (15.02 vs 20.11 months; P = 0.0028) and a shorter median recurrence-free survival (mRFS) (10.30 vs 15.17 months; P = 0.0028). However, after PSM analyses, there were no differences in OS (mOS 18.6 vs 18.0 months; P=0.24) or RFS (mRFS 10.98 vs 12.02 months; P = 0.39) between the GBNEC and GBADC cases. After multivariate analysis, tumor diagnosis (GBNEC vs GBADC) was not identified as an independent risk factor for shorter RFS (P = 0.506) or OS (P = 0.731). Unfavorable pathological features, including advanced AJCC tumor stages, poor differentiation, presence of LVI, and positive resection margins (all P < 0.05), were independent risk factors for inferior OS and RFS. GBNEC is difficult to diagnose early and has a prognosis comparable to stage-matched poorly differentiated GBADC. Tumor diagnosis (either GBADC or GBNEC) was not an independent risk factor for the patient's OS. Unfavorable pathological features of the neoplasm are the main determinants.

Fusion Oncogenes in Patients With Locally Advanced or Distant Metastatic Differentiated Thyroid Cancer.

Fusion oncogenes are involved in the underlying pathology of advanced differentiated thyroid cancer (DTC), and even the cause of radioactive iodine (RAI)-refractoriness. We aimed to investigation between fusion oncogenes and clinicopathological characteristics involving a large-scale cohort of patients with advanced DTC. We collected 278 tumor samples from patients with locally advanced (N1b or T4) or distant metastatic DTC. Targeted next-generation sequencing with a 26-gene ThyroLead panel was performed on these samples. Fusion oncogenes accounted for 29.86% of the samples (72 rearrangement during transfection (RET) fusions, 7 neurotrophic tropomyosin receptor kinase (NTRK) fusions, 4 anaplastic lymphoma kinase (ALK) fusions) and occurred more frequently in pediatric patients than in their adult counterparts (P = .003, OR 2.411, 95% CI 1.329-4.311) in our cohort. DTCs with fusion oncogenes appeared to have a more advanced American Joint Committee on Cancer (AJCC)_N and AJCC_M stage (P = .0002, OR 15.47, 95% CI 2.54-160.9, and P = .016, OR 2.35, 95% CI 1.18-4.81) than those without. DTCs with fusion oncogenes were associated with pediatric radioactive iodine (RAI) refractoriness compared with those without fusion oncogenes (P = .017, OR 4.85, 95% CI 1.29-15.19). However, in adult DTCs, those with fusion oncogenes were less likely to be associated with RAI refractoriness than those without (P = .029, OR 0.50, 95% CI 0.27-0.95), owing to a high occurrence of the TERT mutation, which was the most prominent genetic risk factor for RAI refractoriness in multivariate logistic regression analysis (P < .001, OR 7.36, 95% CI 3.14-17.27). Fusion oncogenes were more prevalent in pediatric DTCs than in their adult counterparts and were associated with pediatric RAI refractoriness, while in adult DTCs, TERT mutation was the dominant genetic contributor to RAI refractoriness rather than fusion oncogenes.

Comparison of clinicopathological characteristics and survival outcomes between gallbladder mucinous adenocarcinoma and gallbladder adenocarcinoma: A propensity score-matched study.

Gallbladder mucinous adenocarcinoma (GBMAC) is a rare subtype of gallbladder adenocarcinoma (GBAC), with limited knowledge of its survival outcomes from small case series and single-center retrospective analysis. To compare the clinicopathological characteristics of GBMAC with typical GBAC and its prognostic factors to gain insights into this field. This study was conducted using data from the Surveillance, Epidemiology, and End Results database, including cases of GBMAC and typical GBAC diagnosed from 2010 to 2017. The Pearson chi-square test or Fisher exact test was used to examine the differences in clinicopathological features between these two cohorts. In addition, propensity score matching (PSM) analysis was performed to balance the selection biases. Univariate and multivariate Cox hazards regression analyses were performed to determine independent prognostic factors for cancer-specific survival (CSS) and overall survival (OS). The Kaplan-Meier curves and log-rank tests were used to assess the OS and CSS of GBMAC and typical GBAC patients. The clinicopathological and demographic characteristics of GBMAC were different from typical GBAC. They included a larger proportion of patients with unmarried status, advanced American Joint Committee on Cancer (AJCC) stage, higher T stage, higher N1 stage rate and lower N0 and N2 stage rates (P < 0.05). Multivariate analyses demonstrated that surgery [OS: Hazard ratio (HR) = 2.27, P = 0.0037; CSS: HR = 2.05, P = 0.0151], chemotherapy (OS: HR = 6.41, P < 0.001; CSS: HR = 5.24, P < 0.001) and advanced AJCC stage (OS: Stage IV: HR = 28.99, P = 0.0046; CSS: Stage III: HR = 12.31, P = 0.015; stage IV: HR = 32.69, P = 0.0015) were independent prognostic indicators for OS and CSS of GBMAC patients. Furthermore, after PSM analysis, there was no significant difference between GBMAC and matched typical GBAC patients regarding OS (P = 0.82) and CSS (P = 0.69). The biological behaviors of GBMAC are aggressive and significantly different from that of typical GBAC. However, they show similar survival prognoses. Surgery, chemotherapy, and lower AJCC stage were associated with better survival outcomes. Further research is needed in the future to verify these results.

Characteristics, Clinical Outcomes, and Prognosis of Anal and Pouch-related Carcinoma in Patients With Crohn's Disease.

This study described the clinical characteristics, outcomes, and prognosis of Crohn's disease (CD) patients with anal cancer in a tertiary referral center. The electronic medical records of 35 adult CD patients, including CD of the pouch, with anal carcinoma evaluated at Mayo Clinic Rochester, Florida, or Arizona between January 1989 and August 2022 were retrospectively reviewed. Before cancer diagnosis, patients with pouch-related carcinoma had a shorter median duration of inflammatory bowel disease than those with anal carcinoma (10 vs 26 years). Twenty-six patients (74%) had perianal diseases or rectovaginal fistula, and 35% had a history of human papillomavirus infection. Twenty-one patients (60%) were diagnosed with cancer by anal examination under anesthesia (EUA). More than half of adenocarcinomas were mucinous. Sixteen patients (47%) were American Joint Committee on Cancer (AJCC) Tumor Nodes Metastasis (TNM) stage 3, and 83% were treated by surgery. At last follow-up, 57% of patients were alive without cancer. The 1-, 3- and 5-year overall survival rates were 93.8% (95% confidence interval [CI], 85.7%-100%), 71.5% (95% CI, 56.4%-90.7%), and 67.7% (95% CI, 51.2%-87.7%), respectively. Advanced AJCC TNM stage (hazard ratio, 3.20 per stage; 95% CI, 1.05-9.72; P = .040) was significantly associated with increased risk of death, whereas the period of cancer diagnosis in 2011-2022 (HR, relative to 1989-2000, 0.16; 95% CI, 0.04-0.72; P = .017) was significantly related to decreased risk of death. Anal and pouch-related carcinomas were rare complications of CD, and long-standing perianal diseases were an important risk factor. Anal EUA improved the diagnostic yield. Newer cancer treatment strategies and surgery were associated with excellent survival outcome.

Clinical Characteristics and Predictive Outcomes of Recurrent Nasopharyngeal Carcinoma-A Lingering Pitfall of the Long Latency.

Simple SummaryUnlike other head and neck cancers, nasopharyngeal carcinoma (NPC) with long-latent recurrence (>five years) is not rare. This study aims to investigate the clinical characteristics and outcomes of long-latent recurrent NPC. We found that 8.1% recurrence occurred after five years. About two thirds of these patients’ primary cancer belonged to the early stages, and almost half of the recurrence was a local recurrence. The five-year overall survival and disease-specific survival rate of long-latent recurrence was 19.7% and 24.5%, respectively. Most long-latent local recurrence was found in unresectable rT3 or rT4 cases, while one-third could not be detected by endoscopy due to recurrence in the skull base. A higher percentage of patients who died after long-latent recurrence were symptomatic with a follow-up interval more than six months, reflecting that delayed detection of recurrence may have a great impact on survival outcome. A long-term follow-up is necessary for early detection of NPC recurrence even after five years of disease-free interval.Purpose: To investigate the clinical characteristics, risk factors, and clinical outcomes of long-latent recurrence (>five years) of nasopharyngeal carcinoma (NPC). Methods: This retrospective study enrolled newly diagnosed NPC patients from the Chang Gung Research Database between January 2007 and December 2019. We analyzed the patients’ characteristics and survival outcomes after recurrence. Results: A total of 2599 NPC patients were enrolled. The overall recurrence rate was 20.5%, while 8.1% of patients had long-latent recurrence (>five years). These patients had a higher percentage of initial AJCC (The American Joint Committee on Cancer) stage I/II (60.5%, p = 0.001) and local recurrence (46.5%, p < 0.001). Unresectable rT3 and rT4 were found in 60% of patients when recurrence and 30% of local recurrence occurred in the skull base, which could not be detected by the regular endoscopy. The five-year overall survival rate of long-latent recurrence was 19.7%. Alive patients tended to be asymptomatic but have regular follow-ups with the interval less than six months. Multivariate analysis showed age and initial advanced AJCC stages were independent risk factors of death after recurrence. In contrast, patients with recurrence between two and five years, salvage surgeries, and regional recurrence had favorable survival outcomes. Conclusion: Long-latent NPC recurrence is not rare, and the survival outcome is poor. Regular follow-up for early detection of NPC recurrence is necessary even after five years of disease-free period.

Pan-Cancer Analysis of the Oncogenic and Immunological Role of RCN3: A Potential Biomarker for Prognosis and Immunotherapy.

Despite emerging publications have elucidated a functional association between RCN3 and tumors, no evidence about a pan-cancer analysis of RCN3 is available. Our study first conducted a comprehensive assessment of its expression profiles, prognosis value, immune infiltration, and relevant cellular pathways via bioinformatics techniques based on the public database of TCGA (The Cancer Genome Atlas). RCN3 is highly expressed in most tumors, and it is associated with poor prognosis. Kaplan-Meier analysis and Cox regression analysis suggested that the high expression of RCN3 was associated with poor overall survival (OS) in pan-cancer, Cox regression analysis also indicated high RCN3 expression was correlated with disease-specific survival (DSS) and progression-free interval (PFI) in most tumors. We observed a regulation function of RCN3 at genetic and epigenetic levels through CNA and DNA methylation using cBioPortal database. Based on Gene Set Enrichment Analysis, we first identified related pathways of RCN3 and its potential biological functions in pan-cancer, RCN3 was implicated in oncogenic pathways, and was related to extracellular matrix and immune regulation. We found that RCN3 positively correlated with the levels of infiltrating cells such as TAMs and CAFs, but negatively correlated with CD8+ T-cells by analyzing immune cell infiltration data we downloaded from published work and online databases, further investigation of the correlation between immunosuppressive genes, chemokines, chemokines receptors, and high RCN3 expression showed a significant positive association in the vast majority of TCGA cancer types. These results indicated its role as an immune regulatory in cancers and suggested that RCN3 is a potential biomarker for immunotherapy. Also, we found that expression of RCN3 was much higher in CRC tissues than in normal tissues with a higher expression level of RCN3 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size, and poor prognosis of CRC. Biological function experiments showed that RCN3 regulated CRC cells’ proliferation and metastasis ability. Upregulation of RCN3 in CRC cells increased the expression of immune related factor, including TGFβ1, IL-10, and IL-6. Thus, our pan-cancer analysis offers a deep understanding of potential oncogenic roles of RCN3 in different cancers.

Iris melanoma: factors predictive of post-management secondary glaucoma in 271 cases at a Single Ocular Oncology Centre.

To identify factors predictive of post-management secondary glaucoma in eyes with iris melanoma. Patients with iris melanoma who were conservatively managed on the Ocular Oncology Service, Wills Eye Hospital from 1970 to 2016 were included. Charts were retrospectively reviewed, and binary logistic regression analysis was performed. Main outcome measures were factors predictive of post-management glaucoma, defined as intraocular pressure (IOP) > 22 mmHg following melanoma treatment. Of 271 patients with iris melanoma, melanoma-related glaucoma was identified in 40 (15%) at presentation and post-management glaucoma developed in 75 (28%) at a mean of 103.7 months (range:1.0-120.0). Comparison (post-management glaucoma vs. no glaucoma) revealed patients with post-management glaucoma presented with worse visual acuity (20/50-20/150) (17% vs. 5%, p = 0.001), increased mean tumour basal diameter (5.1 mm vs. 4.3 mm, p = 0.004), greater melanoma-related increased IOP on presentation (24.1 mmHg vs. 16.2 mmHg, p < 0.001), diffuse tumour shape (9% vs. 4%, p = 0.01), American Joint Committee on Cancer (AJCC) T4 category (7% vs. 2%, p = 0.03), and extraocular tumour extension (7% vs. 2%, p = 0.03). Risk factors for post-management glaucoma identified by multivariate analysis included melanoma-related increased IOP at presentation (OR:1.1, [1.08-1.22] per 1-mmHg increase, p < 0.001), increased mean tumour basal diameter (OR:1.17, [1.02-1.33] per 1-millimetre increments, p = 0.03), advanced AJCC clinical T subcategory (OR:1.23, [1.04-1.46] per 1-subcategory increments, p = 0.02) and plaque radiotherapy treatment (OR:2.32, [1.13-4.75], p = 0.02). Features of iris melanoma that predicted post-management glaucoma included melanoma-related increased IOP on presentation, advanced AJCC clinical T subcategory, increased mean tumour basal diameter, and plaque radiotherapy treatment.

Prevalence of Delta-Like Protein 3 in a Consecutive Series of Surgically Resected Lung Neuroendocrine Neoplasms.

Delta-like protein 3 (DLL3) is a protein of the Notch pathway, and it is a potential therapeutic target for high-grade lung neuroendocrine tumors (NETs), i.e., small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). However, DLL3 prevalence in lung NETs and its association with clinicopathological characteristics and prognosis remained unclear. We analyzed the immunohistochemical expression of DLL3 and its prognostic role in a consecutive series of 155 surgically resected lung NETs, including typical carcinoid (TC), atypical carcinoid (AC), LCNEC, and SCLC patients. The DLL3 expression was categorized as high (>50% positive tumor cells) or low (<50%). In addition, tumors were categorized by H-score (i.e., percentage of positive cells by staining intensity, ≥150 vs. <150). DLL3 staining was positive in 99/155 (64%) samples, and high DLL3 expression was frequently observed in high-grade tumors. In detail, 46.9% and 75% of SCLC and 48.8% and 53.7% of LCNEC specimens showed a high DLL3 expression by using H-score and percentage of positive tumor cells, respectively. Regarding low-grade NETs, only 4.9% and 12.2% TCs and 19.5% and 24.4% ACs had high DLL3 expression considering H-score and percentage of positive tumor cells, respectively. High DLL3 expression was associated with advanced American Joint Committee on Cancer (AJCC) stage, peripheral location, and chromogranin A expression in high-grade tumors (p < 0.05). In low-grade NETs, high DLL3 expression was associated with female sex, peripheral location, a higher number of mitoses, higher Ki-67 index, presence of necrosis, and pleural infiltration (p < 0.05). No association was observed between high DLL3 expression and overall survival (OS) and disease-free survival (DFS) in high-grade NETs, whereas high DLL3 expression was associated with lower DFS in ACs (p = 0.01). In conclusion, our study demonstrated a high prevalence of DLL3 expression in high-grade lung NET patients and its association with aggressive clinicopathological features. These findings confirm that DLL3 could represent a useful biomarker for target therapy in high-grade tumors. Our results also suggest that the DLL3 expression could identify a subset of AC tumors with more aggressive behavior, thus providing the basis for new therapeutic options in this group of patients.

Association between mutation profiles and clinicopathological features in Chinese patients with thyroid cancer

AbstractRecently, mutation profiles provided new insights into comprehensive understanding of TC biology by Next Generation Sequencing (NGS). We explored association between mutation profiles and clinicopathological features in Chinese patients with thyroid cancer (TC). Two hundred and twenty‐five formalin‐fixed, paraffin‐embedded tissue specimens from surgically removed thyroid samples were detected with 15 target genes by NGS. Mutation profiles and clinicopathological features were analyzed. Two hundred and seven mutations including two hundred mutations in 81.40% papillary thyroid carcinoma samples, three mutations in 50.00% MTC samples, and four mutations in 100% anaplastic thyroid carcinoma samples were detected. There were 19.56% samples without any mutations in target genes, 69.78% samples harbored mutations in single gene, 9.78% samples carried two gene mutations, and 0.89% samples had triple different gene mutations. For PTC, BRAF mutations were predominant, TERT mutations are more prevalent in advanced PTC and RET fusion was only observed among the PTC. For MTC, RET point mutations were predominant. For samples carried more than one gene mutations, the allelic frequency of mutants were almost similar. Multiple mutations in TC patients were significantly more frequent in cases of patients aged 55 and over (p &lt;.001) and advanced American Joint Committee on Cancer (AJCC) cancer stage (p &lt;.001). Gender (p = .309) and pathological subtype (p = .121) did not show significant correlation with mutations. Analysis between mutation profiles and clinicopathological features provides new insights into the biology of TC and is expected to increase the accuracy of diagnosis and prognostication in TC, leading to improved precision treatment for TC patients.

High vimentin expression with E-cadherin expression loss predicts a poor prognosis after resection of grade 1 and 2 pancreatic neuroendocrine tumors

BackgroundPancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms with malignant behaviors that can develop from inert slow growth or low malignancy to aggressive metastasis during follow-up. Recently, vimentin and E-cadherin were shown to be prognostic markers in some malignant tumors but were not evaluated in pNETs. The aim of this study was to evaluate the expression and prognostic significance of vimentin and E-cadherin in grade 1 and 2 pNETs.MethodsA retrospective review of 227 patients with grade 1 and 2 pNETs undergoing surgical resection was conducted. Tumor specimens were immunohistochemically stained for vimentin and E-cadherin. Correlations between vimentin and E-cadherin expression and other clinicopathological features were then analyzed. Furthermore, overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier and univariate and multivariate Cox regression methods.ResultsAmong 227 patients, 55 (24.2%) harbored tumors with high vimentin expression, while 117 (51.5%) harbored tumors with loss of E-cadherin expression. Patients with high vimentin expression and loss of E-cadherin expression had significantly elevated risks of lymph node metastasis, distant metastasis, perineural invasion and an advanced American Joint Committee on Cancer (AJCC) stage compared with those with low vimentin expression and preserved E-cadherin expression, high vimentin expression and preserved E-cadherin expression, or low vimentin expression and loss of E-cadherin expression. Furthermore, multivariate analysis showed that high vimentin expression with loss of E-cadherin expression was an independent predictor of OS and DFS in patients with grade 1 and 2 pNETs who underwent resection (both P < 0.001).ConclusionsThe current study demonstrated that high vimentin expression with loss of E-cadherin expression was correlated with lymph node metastasis, distant metastasis, disease progression and a poor prognosis in patients with grade 1 and 2 pNETs who underwent resection.

Survival Analysis of Radiation Therapy in Ovarian Cancer: A SEER Database Analysis.

Results A total of 20031 ovarian cancer patients were included, with 291 (1.45%) patients who received radiotherapy. The median overall survival (OS) in patients who received radiotherapy was shorter than which in patients without radiotherapy (23 vs. 75 months, P < 0.001). The Elderly, nonepithelial pathology, advanced American Joint Committee on Cancer (AJCC) stage, elevated level of CA125, and receiving radiotherapy were risk predictors to survival in both multivariable analyses before and after PSM. Among 11872 patients with III/IV stage, the radiotherapy group also showed a significantly worse prognosis (median OS: 19 vs. 44 months in patients without radiotherapy, P < 0.001). Consistent results were observed in stratification analyses on pathology and stage among patients with III/IV stage. Conclusions For patients with ovarian cancer, radiotherapy was associated with a poor prognosis regardless of pathology or stage. Considering this is a retrospective study, future studies concerning radiotherapy combination with other new agents in ovarian cancer are needed.

The prognostic role of the preoperative systemic immune-inflammation index and high-sensitivity modified Glasgow prognostic score in patients after radical operation for soft tissue sarcoma

IntroductionThe prognostic values of nutritional and immune-inflammatory indicators in non-metastatic soft tissue sarcoma (STS) patients are not clear. We investigated the utility of systemic immune-inflammation index (SII) and the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in the prediction of STS patient's prognosis. Materials and methodsPatients admitted between January 2000 and December 2016, who underwent R0 resection for STS at SYSUCC were carefully retrospectively reviewed, and 454 patients were enrolled. The laboratory data and clinical data were collected from the patient's record. ROC analysis is used to determine the optimal cutoff value. Survival curves were analysed by Kaplan-Meier method. Cox proportional hazard model was used to find out prognostic variables. ResultsIncreased SII and Hs-mGPS values were significantly related to larger tumour size, deep tumour location, higher tumour grade and more advanced American Joint Committee on Cancer (AJCC) stage. Patients with an elevated SII had a shorter median survival time and a lower 5-year OS rate than those with a low SII. And patients with low Hs-mGPS had longer median OS and DFS. Multivariate analysis revealed that both the SII and the Hs-mGPS were independent predictive indicators for OS. And a joint model containing both the Hsm-GPS and the SII appeared to have the strongest predictive ability. ConclusionOur findings indicated that malnutrition and systemic inflammation are risk factors for the survival of STS patients after operation, and early recognition and intervention of malnutrition and systemic inflammation may help to improve the survival of the patients.

LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression.

BackgroundAberrant expression of long noncoding RNAs are implicated in the pathogenesis of human malignancies. LINC00844 expression is dramatically downregulated in prostate cancer, and functional studies have revealed the association between the aberrant expression of LINC00844 and prostate cancer cell invasion and metastasis. However, the function and mechanism of action of LINC00844 in the pathogenesis of hepatocellular carcinoma (HCC) are poorly understood.MethodsLINC00844 and N-Myc downstream-regulated 1 (NDRG1) expression in HCC tissues and cell lines was detected with real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Correlations between LINC00844 expression level and clinicopathological features were investigated using the original data from The Cancer Genome Atlas (TCGA) database. HepG2 and HCCLM9 cell lines were transfected with Lv-LIN00844 virus to obtain LINC00844-overexpressing cell lines. Cell proliferation and cell invasion and migration were examined with the cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, the correlation between LINC00844 and NDRG1 expression was analysed using Pearson’s correlation analysis.ResultsLINC00844 expression was significantly downregulatedin HCC tissues and cell lines, and a statistical correlation was detected between low LINC00844 expression and sex (Female), advanced American Joint Committee on Cancer (AJCC) stage (III + IV), histological grade (G3 + G4), and vascular invasion (Micro and Macro). In vitro experiments showed that LINC00844 overexpression significantly repressed the proliferation, migration, and invasion of HCC cells. NDRG1 expression was higher in HCC tissues and LINC00844 could partly inhibit the expression of NDRG1.

Serum deprivation response functions as a tumor suppressor gene in papillary thyroid cancer.

The mechanism of papillary thyroid cancer (PTC) has shown numerous recurrently mutated genes, but the discovery of abnormal expression of novel tumor suppressor genes has been slow. The aim of our study is to explore the biological functions of SDPR in thyroid cancer. We reanalyzed the RNA-Seq data of PTC from The Cancer Genome Atlas (TCGA) database and found that serum deprivation response (SDPR) was significantly downregulated in PTC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was performed to assess the expression of SDPR. Both loss- and gain-of-function experiments, and flow cytometry were performed to investigate the functions. SDPR was significantly downregulated in PTC. Reduced expression of SDPR was associated with larger tumor size, more serious lymph node metastasis, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with lower SDPR expression had a shorter recurrence-free survival. SDPR expression and AJCC stage were independent predictors of poor recurrence-free survival (RFS). Moreover, cell proliferation, colony formation, and migration were inhibited after SDPR overexpression, whereas knockdown of SDPR exerted an oncogenic effect. SDPR induction also initiated the mesenchymal-epithelial transition, alongside suppressing AKT signaling and cyclin family expression. Apart from DNA methylation, LOC105373813, may also co-regulate SDPR expression by forming a stable hybrid with SDPR messenger RNA. Our study indicated that SDPR may function as a potential prognostic marker in PTC.

Management and outcomes among patients with sarcomatoid hepatocellular carcinoma: A population‐based analysis

Few data are available regarding the management and outcomes among patients with sarcomatoid hepatocellular carcinoma (HCC) due to its rarity. Patients diagnosed with sarcomatoid HCC from 2004 through 2015 were identified in the National Cancer Data Base. Overall survival (OS) was calculated among patients with sarcomatoid versus conventional HCC using a 1:3 propensity score matching based on sex, age, and American Joint Committee on Cancer (AJCC) stage of disease. The final analytic cohort included 104 patients with sarcomatoid HCC and 312 patients with conventional HCC. Patients with sarcomatoid HCC more often had a larger median tumor size (8.5cm vs 5.4cm; P<.001) and poorly or undifferentiated tumors (52.9% vs 13.8%; P<.001) compared with patients who hadconventional HCC. 5-year OS was worse among patients with sarcomatoid versus conventional HCC (5.7% vs 30.1%; P<.001). Subgroup analysis demonstrated worse 5-year OS among patients with sarcomatoid versus conventional HCC among patientstreated with eithercurative-intent or palliative therapies. Stage-specific subgroup analysis indicated a worse OS amongpatients with AJCC stage I, stage II, or stage III sarcomatoid HCC. On multivariable analysis, uninsured status, advanced AJCC stage (stage III/stage IV), and histological sarcomatoid subtype were independentlyassociated with worse outcomes (all P<.05). Sarcomatoid HCC is a very rare variant of HCC, which wasassociated with larger tumor size and worse tumor grade on presentation. On propensity score matched analyses that controlled for known confounding factors, patients with sarcomatoid HCC hada worse stage-for-stage long-term survival compared with patients who had conventional HCC.

Abstract 4938: Identification of a subtype of hepatocellular carcinoma with poor prognosis based on expression of genes within the glucose metabolic pathway

Abstract Hepatocellular carcinoma (HCC) is the most prevalent primary cancer and a highly aggressive liver malignancy. Liver cancer cells reprogram their metabolic pathways to meet their needs for rapid proliferation and generation of the biomass for tumor growth. The accelerated aerobic glycolysis in tumor has been considered one of the hallmarks that distinguish cancer cells from normal cells. In the present study, liver hepatocellular cancer dataset of the Cancer Genome Atlas (LIHC TCGA) and datasets from Gene Expression Omnibus (GEO) were used to investigate the alterations in expressions of the genes involved in the glucose metabolic pathways as well as their association with the patient clinical stage and survival in liver cancer. In this study, 97 genes including glucose and lactate transporters, the enzymes involved in glucose metabolism (glycolysis, gluconeogenesis, regulation of glucose metabolism, tricarboxylic acid cycle (TCA), pentose phosphate pathway), and glycogen metabolism (glycogen synthesis, glycogen degradation, regulation of glycogen metabolism) were included. The results showed that the expressions of around 50% of genes involved in the glucose metabolic pathway are altered in liver tumors compared to the corresponding normal tissues (p-values&amp;lt;0.005 and fold change≥1.5). More importantly, the differentially expressed genes are associated with advanced AJCC (American Joint Committee on Cancer) clinical stage (p-values&amp;lt;0.05), and reduced overall survival (OS) and recurrence-free survival (RFS) as determined by multivariate Cox proportional hazard models (p-values&amp;lt;0.05). Unexpectedly but interestingly, supervised clustering with the differentially expressed genes of the LIHC TCGA data identified a subgroup of patients with worse OS compared to those patients that clustered with the normal samples (p-value=0.00015, and 5-year median survival time (months) is 25.50 with 95% CI (20.90, 42.37) vs. 47.43 with 95% CI (40.33, NA)). This group of patients had decreased activation (p-values&amp;lt;0.0001) of FXR/RXR and LXR/RXR involved in lipid, cholesterol and glucose metabolism, but had increased atherosclerosis and leukocyte extravasation signaling (p-values&amp;lt;0.0001) activated during inflammation. This indicates those patients had decreased metabolism and increased inflammation which may contribute to the worse OS. Collectively, this study indicates that expressions of the glucose metabolic genes could be used as potential prognostic markers as well as therapeutic targets for liver cancer. Citation Format: Xiaoli Zhang, Kalpana Ghoshal, Lang Li. Identification of a subtype of hepatocellular carcinoma with poor prognosis based on expression of genes within the glucose metabolic pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4938.

Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of T stages in hilar cholangiocarcinoma.

Background: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR)) and different American Joint Committee on Cancer (AJCC) T stages in patients with hilar cholangiocarcinoma.Methods: A total of 101 patients who underwent surgical treatment for hilar cholangiocarcinoma between 2003 and 2014 in Peking Union Medical College Hospital were retrospectively analyzed. Receiver-operating curves were used to calculate optimal cutoff values for the NLR and the PLR. Univariate and multivariate analyses were used to identify whether the NLR and PLR can independently predict different AJCC T stages.Results: Multivariate analysis showed that higher NLR and PLR independently predicted advanced AJCC T stages (OR 3.74, 95% CI 1.09–12.83, P=0.036; and OR 7.86, 95% CI 2.25–27.43, P=0.001, respectively). At a threshold of 2.75, the NLR was 75.9% sensitive and 66.7% specific for different AJCC T stages; at a threshold of 172.25, the PLR was 65.5% sensitive and 80.6% specific.Conclusion: Preoperative NLR and PLR can be used as independent predictors of different AJCC T stages in patients with hilar cholangiocarcinoma.

FAM83D is associated with gender, AJCC stage, overall survival and disease-free survival in hepatocellular carcinoma.

Prognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P<0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005–2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III–IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.

Elevated Controlling Nutritional Status (CONUT) Score is Associated with Poor Long-term Survival in Patients with Low-grade Soft-tissue Sarcomas Treated with Surgical Resection.

Several studies have examined the Controlling Nutritional Status (CONUT) score, which is a screening tool for nutritional status and an effective biomarker for patient survival after cancer treatment. However, its role in soft-tissue sarcoma (STS) remains unknown. Because of the lack of predictive markers for survival in patients with STS, we aimed to determine the CONUT score's association with survival. (1) Is there a relationship between the CONUT score and clinicopathologic characteristics such as tumor size, tumor location, pathological grade, and advanced stage based on the American Joint Committee on Cancer (AJCC) guidelines? (2) Is the CONUT score associated with disease-free survival (DFS) and overall survival (OS) in patients treated surgically for STS, even when compared with other systemic inflammatory response markers? Between 1999 and 2016, 769 patients underwent R0 resection for STS at our institution. Adequate medical records and available followup data were required for inclusion in this study. Exclusion criteria were synchronous inflammatory diseases, unplanned excision, and neoadjuvant therapy. There were 658 patients (86%) who fulfilled all criteria. The minimum followup time was 24 months (median, 103 months; range, 61-147 months). The median age of the patients was 43 years (range, 5-85 years), and 265 patients (40%) were women. All patients had Stage I to IV tumors according to the 8 edition of the AJCC staging system. The grade classification was determined to be G1 in 130 patients (20%), G2 in 304 (46%), and G3 in 201 (31%). The CONUT score was calculated based on the serum albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration. The score ranged from 0 to 12, with higher scores indicating worse nutritional status. The patients were classified into two groups according to a receiver operating characteristic curve analysis: the high (≥ 2) and low (0 or 1) CONUT score groups. There were 435 patients in the low CONUT score group and 223 in the high CONUT score group. We tested for an association between the CONUT scores and gender, age, tumor diameter, tumor depth, tumor grade, and AJCC stage using the chi-square and Fisher's exact methods. We also compared the strength of the association between postoperative survival and the CONUT scores, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) using multivariate Cox proportional hazard model analyses. High CONUT scores were associated with large tumor size (odds ratio [OR], 1.47; 95% CI, 1.06-2.04; p = 0.020), deep tumor location (OR, 1.66; 95% CI, 1.17-2.36; p = 0.004), high tumor grade (OR, 2.54; 95% CI, 1.56-4.14; p = 0.001), and advanced AJCC stage (OR, 1.86; 95% CI, 1.14-3.02; p < 0.001). The low CONUT score group exhibited a higher 5-year OS rate and longer OS than the high CONUT score group (82% versus 65%; odds ratio, 2.45; 95% CI, 1.27-4.72; p < 0.001; 81 versus 64 months, Z = -2.56; p < 0.001). A multivariate analysis indicated that an elevated CONUT score was an independent predictor of OS (hazard ratio [HR], 1.86; 95% CI, 1.47-4.14; p < 0.001) and DFS (HR, 1.63; 95% CI, 1.26-2.11; p < 0.001), but the NLR and PLR were not. In an individual subgroup analysis, the CONUT scores were associated with OS and DFS in the tumor diameter (< 5 or ≥ 5 cm) subgroup, tumor depth (superficial or deep) subgroup, tumor grade (G1 and G2) subgroup, and AJCC stage (I/II or III/IV) subgroup, but not in the G3 subgroup (p = 0.051 and p = 0.065). High CONUT scores were independently associated with aggressive tumor behavior and unfavorable survival for patients with low-grade, but not high-grade, resected STS. If these findings can be substantiated in larger studies, the CONUT score might be useful for predicting survival and help to develop new treatment strategies for nutrition interventions. Level III, therapeutic study.

Underlying liver disease and advanced stage liver cancer are associated with elevated neutrophil-lymphocyte ratio.

Background/AimsInflammation-based scores, such as the neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis in hepatocellular carcinoma (HCC); but variable cut-off values and potential lack of specificity have limited the utility of NLR. This study evaluates NLR in a large cohort of HCC patients.MethodsWe retrospectively reviewed 789 HCC cases (1993–2017) for demographics, tumor characteristics, treatment, and survival. NLR was stratified into NLR ≥1.5 and NLR ≥3 and analyzed for correlation with American Joint Committee on Cancer (AJCC) and Barcelona Clinic Liver Cancer (BCLC) stages. In 235 patients who underwent liver resection, survival and recurrence were evaluated by NLR.ResultsIn 789 HCC cases, mean NLR was increased with advanced AJCC and BCLC stages. Hepatitis C patients were less likely to have NLR ≥1.5 and ≥3. Non-alcoholic steatohepatitis patients were more likely to have NLR ≥3. Patients with tumor size >5 cm, rupture, or macrovascular invasion were more likely to have NLR ≥3. In patients treated with resection, NLR ≥3 predicted early recurrence (odds ratio [OR] 4.14, P<0.01) and overall recurrence (OR 4.05, P<0.01). Mean NLR was 4.30 in those with recurrence and 2.75 in those without recurrence. Patients with NLR ≥3 showed significantly worse survival compared to those with NLR <3 (P<0.01 by log-rank test).ConclusionsElevated NLR is associated with advanced cancer stage and aggressive tumor characteristics, such as large size, rupture, and invasion. NLR ≥3 was associated with early and overall recurrence after resection but varied with etiology. NLR may be a useful biomarker in predicting recurrence for HCC patients undergoing curative resection, but further studies are required to elucidate the effect of disease etiology.