Terms Of Subtypes Research Articles

Facial Dysmorphology in Saethre-Chotzen Syndrome.

Classic features of Saethre-Chotzen syndrome (SCS) described in the literature include a prominent nasal bridge, eyelid ptosis, telorbitism, maxillary hypoplasia, and mandibular prognathism. The purpose of this study was to evaluate objectively the bony features of SCS. Preoperative computer tomography scans of 15 SCS patients, 23 normal controls, 13 bicoronal nonsyndromic, and 7 unicoronal nonsyndromic craniosynostosis patients were included for analysis. Unaffected controls and nonsyndromic patients were age- and sex-matched to SCS patients. Morphometric cephalometrics were analyzed using three-dimensional computer tomography reconstructions. Mann-Whitney U were used to compare facial measurements between SCS and normal and nonsyndromic craniosynostosis controls. Telorbitism was present in bicoronal SCS patients only (P = 0.04) but absent in the unicoronal and bicoronal/metopic cohorts. The angle of the nasal bone relative to the sella was not different between SCS and controls (P = 0.536), although the angle of the nasal bone relative to the forehead was decreased in SCS by 15.5° (P < 0.001). Saethre-Chotzen syndrome had a 2.6° maxillary retrusion relative to controls (P = 0.03). In addition, SCS patients aged 4 to 7 months had a wider (39.34 versus 35.04, P = 0.017) and anteroposteriorly foreshortened (32.12 versus 35.06, P = 0.039) maxilla. There was no difference in mandibular prognathism among SCS patients as measured by the sella-nasion-B point angle compared to controls (P = 0.705). Despite classic descriptions, on morphometric analysis SCS patients did not demonstrate consistency across all suture subtypes in terms of telorbitism, a broad nasal bridge, or mandibular prognathism. Rather, SCS subtypes of SCS based on suture pathology more closely resemble nonsyndromic patients.

Single-Cell Sequencing to Identify Six Heat Shock Protein (HSP) Genes-Mediated Progression Subtypes of Clear Cell Renal Cell Carcinoma.

BackgroundHeat shock proteins (HSPs) are widely involved in tumor occurrence and development and are prognostic markers for multiple tumors. However, the role of HSPs in clear cell renal cell carcinoma (ccRCC) remains unclear.MethodsWe used Cytoscape to identify hub genes in the ccRCC single-cell sequencing data set from the Gene Expression Omnibus (GEO) data repository. We identified subtypes, C1 and C2, of The Cancer Genome Atlas (TCGA) patients based on the expression of hub genes using unsupervised consensus clustering. Principal component analysis (PCA) was used to verify the clustering differences, and Kaplan–Meier (K-M) estimate was used to verify the survival differences between C1 and C2 patients. We used TIMER 2.0 and CIBERSORT to evaluate the immune cell infiltration of HSP genes and C1 and C2 patients. The R package “pRRophetic” was used to evaluate the sensitivity in C1 and C2 patients to the four first-line treatment drugs.ResultsWe identified six hub genes (HSP90AA1, HSPH1, HSPA1B, HSPA8, and HSPA1A) encoding HSP, five of which were significantly downregulated in TCGA group, and four had a protective effect on prognosis (p <0.05). Survival analysis showed that C1 patients had a better overall survival (p <0.001). TIMER 2.0 analysis showed that three HSP genes were significantly correlated with the infiltration of CD4+ T cells and CD4+ Th1 cells (|cor|>0.5, p<0.001). CIBERSORT showed significant differences in multiple infiltrating immune cells between C1 and C2 patients. Meanwhile, the expression of PD1 was significantly lower in C1 patients than in C2 patients, and the expression of PDL1 is the another way around. Drug sensitivity analysis showed that C1 patients were more sensitive to sorafenib, pazopanib, and axitinib (p <0.001).ConclusionOur research revealed two molecular subtypes of ccRCC based on 6 HSP genes, and revealed significant differences between the two subtypes in terms of clinical prognosis, immune infiltration, and drug sensitivity.

Comparison of the effects of rutaecarpine on molecular subtypes of breast cancer

Natural compounds have gained considerable attention in recent years due to disadvantages and properties of current chemotherapy drugs in cancer therapy. In addition, the impact of these compounds is specific for each type and/or subtypes of cancer due to different treatment response. Rutaecarpine, an alkaloid obtained from Evodia Rutaecarpa Chinese herb, has anticancer activity by inhibiting topoisomerase and/or cyclo-oxygenase-2 levels. However, the effectiveness of rutaecarpine has not been well known in breast cancer in terms of subtype. Therefore, we investigated the potential therapeutic effects of rutaecarpine on two different subtypes of breast cancer cells. The cytotoxic and apoptotic effects of rutaecarpine on MCF-7 and MDA-MB-231 cells were analyzed by WST-1, Annexin V, cell cycle, and acridine orange staining. WST-1 results indicated that rutaecarpine significantly inhibited the growth of both cancer cells for 48 h (P < 0.05). In addition, rutaecarpine treatment caused apoptotic cell death through chromatin condensation and nuclear blebbing and G0/G1 arrest in both breast cancer cells. However, the efficacy of rutaecarpine was more profound in MCF-7 cells than MDA-MB-231 cells. Consequently, rutaecarpine has a potential therapeutic effect on breast cancer. However, the effectiveness of rutaecarpine is dependent on the subtype of breast cancer.

Evaluating differential cost growth across individual cancers: Insights from Oncology Care Model data.

e18853 Background: Analyzing cost growth in oncology often faces significant challenges, including fragmentation of data for infused vs. oral agents and ascertaining the cost of inpatient care. How differential cost growth at the individual cancer level contributes to aggregate cost growth in oncology is often opaque. We leverage the integrated claims data provided by Medicare for its Oncology Care Model (OCM) pilot to analyze variations across individual cancers with respect to cost growth. Methods: OCM’s innovative methodology creates a natural experiment where costs are compared against a counterfactual comprised of Medicare patients seen in non-OCM practices. Leveraging this differential counterfactual provides an opportunity to gain insight into cost growth for individual cancers compared to oncology as a whole. Specifically, cost growth is measured each Performance Period (PP) with respect to the Baseline Period, from 2012 to 2015. We analytically decomposed and remodeled key quantitative factors in OCM associated with cost dynamics in oncology, including the Trend Factor (TF), which represents non-OCM cost growth. From 124,896 episodes, we sampled with replacement 19,191 episodes from 17 practices between PP1 and PP6 using empirical data distributions. We assumed neutral novel therapy and experience adjustments and then compared the overall TF to the remodeled cancer-level TF, reaggregated from the individual episodes. Results: Reallocating the TF reveals that cost growth among cancer types is highly variable in the broader Medicare population. Cost growth at the individual cancer level varied from +99.3% to -14.3%. Of the 21 OCM cancers, 18 have TFs greater than zero, indicating cost growth in the non-OCM Medicare population since the Baseline Period. Four have a TF greater than 50%. Three cancer types show decreasing costs relative to the baseline period: intestinal cancer, MDS, and CNS tumor. Conclusions: Significant variation exists across individual cancer subtypes in terms of cost growth. Aggregate analyses of cancer at large have insufficient specificity to rationalize payment mechanisms. Payment reform efforts within cancer care should directly address dynamics at the individual cancer or cancer subtype level in order to provide more valid considerations for expected resource utilization, including in future payment policies. [Table: see text]

Do Distinct Groups of Reactively and Proactively Aggressive Children Exist? A Confirmatory Latent Profile Approach

The present study examined whether there are distinct groups of children with reactive versus proactive motives for their aggressive behavior. We extended previous research by using a person-based analytical approach on data from a questionnaire assessing children’s motives independently from the severity of their aggression. Two competing hypotheses were tested. The both subtypes hypothesis holds that both reactive and proactive subtypes exist, as well as a mixed subtype. The reactive only hypothesis holds that only reactive and mixed subtypes exist. Hypotheses were tested on existing data from a community sample of children displaying aggression (Study 1: n = 228, ages 10–13, 54% boys), and two clinical samples of children with aggressive behavior problems (Study 2: n = 115, ages 8–13, 100% boys; Study 3: n = 123, ages 6–8, 78% boys). Teachers reported on children’s reactive and proactive motives. We selected measures available from peers, parents, teachers, and children themselves to compare the supported subtypes on variables that previous literature suggests uniquely correlate with reactive versus proactive aggression. Confirmatory latent profile analyses revealed that the both subtypes hypothesis best fit the data of all three samples. Most children were classified as reactive (55.7–61.8% across samples), with smaller percentages classified as proactive (10.4–24.1%) and mixed (18.0–33.9%). However, these subtypes only differed in expected directions on 7 out of 34 measures. Overall, results support the existence of both reactive and proactive subtypes of aggressive children, but the distinctiveness of these subtypes in terms of social-emotional characteristics warrants further study.

Abstract PS6-07: Comparison of breast cancer staging models in patients after neoadjuvant chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NAC) is commonly utilized for breast cancer, however no consensus exists on the best way to stage these patients following treatment. Importantly, the American Joint Commission on Cancer (AJCC) 8th edition staging system did not specifically address staging after NAC. However, previous work by our group has shown that the pathologic prognostic stage does stratify patients with respect to outcomes. Our objective was to compare performance of the AJCC pathologic prognostic staging system to a second staging model, the Residual Cancer Burden (RCB) Index which takes into account residual tumor size, cellularity, lymph node status and size of any lymph node metastases. Methods: A retrospective review identified patients with stage I-III invasive breast cancer treated with NAC from 2004-2014 at Dana-Farber Cancer Institute. Patients were excluded if they did not have RCB reported on final pathology. Disease-free survival (DFS) was defined as any recurrence or death from any cause, and overall survival (OS) as death from any cause. DFS and OS were calculated using the Kaplan-Meier method for each staging model. Receiver operator characteristic (ROC) curves were used to assess model fit using the c-statistic and the Hanley method to compare c-statistics. Results: A total of 802 patients underwent NAC for stage I-III breast cancer. The median age was 48 years (range 22-86). Most patients presented with cT2 (n=470, 58.6%) or cT3 (n=188, 23.4%) and cN1 (n=422, 52.6%) disease. The majority (n=563, 70.2%) presented with grade 3 disease. In terms of subtype, 296 (36.9%) patients had hormone receptor-positive, HER2 negative, 261 (32.5%) HER2+, and 245 (30.5%) triple negative disease. Median follow up was 79.5 months (range 4-169). There were 176 recurrences including 32 local, 25 regional, and 145 distant recurrences. 676 (76.8%) patients were alive at last follow-up. The Table depicts the 7-year DFS and OS estimates for each of the staging models. The ROC c-statistics for DFS model fit were statistically similar, 0.72 for AJCC pathologic prognostic stage and 0.71 for RCB (p=NS). The c-statistics for OS were 0.74 and 0.71 respectively (p=NS). Conclusions: Our results provide additional external validation of the AJCC pathologic prognostic stage and RCB’s ability to stratify patients after NAC with respect to survival outcomes. These data can be used to inform subsequent revisions of the AJCC breast cancer staging system. Estimated 7-year DFS and OS in Potential Staging Models for Breast Cancer Patients after NAC (n=802)7yr-DFS7yr-OSPathologic Prognostic StageStage 0 (n=228)92.9%94.8%Stage IA (n=193)81.7%90.2%Stage IB (n=173)74.5%86.6%Stage IIA (n=105)62.2%71.5%Stage IIB (n=11)70.2%57.3%Stage IIIA (n=40)62.2%75.4%Stage IIIB (n=27)56.7%83.0%Stage IIIC (n=25)27.8%28.2%C-statistic (95% CI)0.72 (0.68-0.76)0.74 (0.69-0.79)RCB0 (n=226)93.5%94.8%I (n=118)83.0%90.0%II (n=278)75.9%85.0%III (n=180)55.1%69.9%C-statistic (95% CI)0.71 (0.67-0.75)0.71 (0.66-0.75) Citation Format: Olga Kantor, Alison Laws, Ricardo G Pastorello, Stephanie Wong, Tanujit Dey, Stuart Schnitt, Tari A King, Elizabeth A Mittendorf. Comparison of breast cancer staging models in patients after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-07.

Single-cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation characteristics.

ObjectivesMuch of the information to date in terms of subtypes and function of bladder urothelial cells were derived from anatomical location or by the expression of a small number of marker genes. To have a comprehensive map of the cellular anatomy of bladder urothelial cells, we performed single‐cell RNA sequencing to thoroughly characterize mouse bladder urothelium.Materials and methodsA total of 18,917 single cells from mouse bladder urothelium were analysed by unbiased single‐cell RNA sequencing. The expression of the novel cell marker was confirmed by immunofluorescence using urinary tract infection models.ResultsUnsupervised clustering analysis identified 8 transcriptionally distinct cell subpopulations from mouse bladder urothelial cells. We discovered a novel type of bladder urothelial cells marked by Plxna4 that may be involved with host response and wound healing. We also found a group of basal‐like cells labelled by ASPM that could be the progenitor cells of adult bladder urothelium. ASPM+ urothelial cells are significantly increased after injury by UPEC. In addition, specific transcription factors were found to be associated with urothelial cell differentiation. At the last, a number of interstitial cystitis/bladder pain syndrome–regulating genes were found differentially expressed among different urothelial cell subpopulations.ConclusionsOur study provides a comprehensive characterization of bladder urothelial cells, which is fundamental to understanding the biology of bladder urothelium and associated bladder disease.

A comparative study of PCS and PAM50 prostate cancer classification schemes

BackgroundTwo prostate cancer (PC) classification methods based on transcriptome profiles, a de novo method referred to as the “Prostate Cancer Classification System” (PCS) and a variation of the established PAM50 breast cancer algorithm, were recently proposed. Both studies concluded that most human PC can be assigned to one of three tumor subtypes, two categorized as luminal and one as basal, suggesting the two methods reflect consistency in underlying biology. Despite the similarity, differences and commonalities between the two classification methods have not yet been reported.MethodsHere, we describe a comparison of the PCS and PAM50 classification systems. PCS and PAM50 signatures consisting of 37 (PCS37) and 50 genes, respectively, were used to categorize 9,947 PC patients into PCS and PAM50 classes. Enrichment of hallmark gene sets and luminal and basal marker gene expression were assessed in the same datasets. Finally, survival analysis was performed to compare PCS and PAM50 subtypes in terms of clinical outcomes.ResultsPCS and PAM50 subtypes show clear differential expression of PCS37 and PAM50 genes. While only three genes are shared in common between the two systems, there is some consensus between three subtype pairs (PCS1 versus Luminal B, PCS2 versus Luminal A, and PCS3 versus Basal) with respect to gene expression, cellular processes, and clinical outcomes. PCS categories displayed better separation of cellular processes and luminal and basal marker gene expression compared to PAM50. Although both PCS1 and Luminal B tumors exhibited the worst clinical outcomes, outcomes between aggressive and less aggressive subtypes were better defined in the PCS system, based on larger hazard ratios observed.ConclusionThe PCS and PAM50 classification systems are similar in terms of molecular profiles and clinical outcomes. However, the PCS system exhibits greater separation in multiple clinical outcomes and provides better separation of prostate luminal and basal characteristics.

The Interchondral Joints of Thorax in Microtia Surgery: Classification and Fabrication Strategies.

The interchondral joint between the sixth and seventh costal cartilages, called synchondrosis, assists in harvesting and fabricating the microtia framework. However, its looseness often complicates the microtia surgery. We aimed to classify the interchondral joints based on looseness and identify predictors for each subtype. Electronic chart and intraoperative photographs were reviewed for consecutive microtia patients who underwent costal cartilage graft for ear reconstruction from June 2001 to February 2020. The sixth and seventh costal interchondral joint was classified in the ascending order of looseness-direct cartilaginous fusion (class I), synovial joint (class II), and loose tissue (class III)-with a minor modification from the cadaveric study of Dr. Briscoe in 1925. χ2 Tests compared the incidence of each subtype in terms of patient variables including age, sex, chest laterality, and radiologic chest deformity. Multivariate logistic regression was used for identifying independent predictors for each subtype. Seven hundred thirty-three graft specimens were enrolled (mean age 12.1 years). Class I joint was seen in 137 (18.7%) grafts, class II in 544 (74.2%), and class III in 52 (7.1%). Female predilection was found for cartilaginous fusion (class I) (adjusted odds ratio, 1.691; P = 0.007). The incidence of loose joint (class III) was comparable, ranging from 4.6% to 12.5%, in terms of all the patient variables. Loose interchondral joints were not uncommon in microtia surgery. Patient variables were less likely to predict this anatomical variation, necessitating some knowledge of managing the framework instability. Female patients were more likely to enable easy fabrication with directly fused costal cartilages.

The role of acoustic radiation force impulse imaging in the diagnosis of cervical carcinoma

Aim: To investigate the diagnostic value of acoustic radiation force impulse imaging in the detection of cervical cancer, and to assess the contribution of this imaging method in distinguishing histological subtypes of cervical carcinoma.Materials and Methods: Twenty four patients with malignant cervical mass and 25 healthy volunteers were included in this prospective study. Ultrasonographic evaluation were performed using a 3.5–6-MHz convex abdominal transducer and adequate software for performing elastographic examinations in quantitative acoustic radiation force impulse mode (Virtual Touch Quantification®). Every examination consisted of at least three independent shear wave velocity measurements. The mean shear wave velocity values were calculated, and used for statistical analysis. Postoperative pathology results of the lesions were used as the reference standard.Results: The mean shear wave velocity values were calculated as 2.79±1.03 m/s in cervical carcinomas, and as 1.86±0.62 m/s in control group. The mean shear wave velocity value of cervical carcinomas was significantly higher than the control group (p=0.003). The mean shear wave velocity values in squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma subtypes were calculated as 2.78±0.93 m/s, 3.16±1.46 m/s, and 1.90±0.21 m/s, respectively. There were no significant differences between cervical carcinoma subtypes in terms of their shear wave velocity values (p=0.247).Conclusion: Acoustic radiation force impulse imaging is a non-invasive and cost-effective, promising adjunct modality that enables objective quantitative measurement, which may contribute to the diagnosis of malignant cervical masses.

Characteristics and prognosis of female breast cancer in Guangzhou, 2008-2017

Objective: To describe the distributions of demographic and clinic pathological characteristics and relations with survival on female breast cancer patients in Guangzhou from 2008 to 2017. Methods: The baseline information of the subjects was obtained from the Guangzhou cancer registry and the outcomes were from the Cancer Follow-up System of Guangzhou. Kaplan-Meier was used to calculate the 1-, 3-, 5-year overall survival rates. Univariate and multivariate Cox proportional hazards regression models were used to identify the factors related to the overall survival. Results: Among the 12 465 breast cancer patients recruited in the study, the average age at diagnosis was 53.9 years old, with those aged 45 to 54 making up the largest proportion (43.9%). Only 15.6% of the patients had college or above degrees. Patients with normal BMI accounted for 78.2%. Most of the patients (90.0%) had received surgical treatment. Invasive ductal carcinoma appeared the most common histologic type, accounting for 82.3%. Among the 2 640 patients diagnosed in the four large hospitals, clinical stages 0-Ⅰ, Ⅱ, Ⅲ and Ⅳ accounted for 35.0%, 44.8%, 17.2% and 3.0%, respectively. The proportions of ER-positive, PR-positive and HER-2 positive breast cancer were 79.5%, 70.8%, and 19.2%, respectively. In terms of subtypes, Luminal B was the most common one, accounted for 53.3%. The 1-, 3- and 5-year overall survival rates were 99.0%, 95.3% and 92.1%, respectively. Results from the multivariate analysis indicated that factors as: age over 55 years old at diagnosis, advanced TNM stage, ER negative, PR negative, Luminal B subtype and triple-negative subtype were associated with poorer prognosis. Conclusions: Compared with the previous hospital-based studies in China, this population-based study revealed that the proportions of patients with advanced age, early clinical stage or ER positive breast cancer were relatively high and the overall survival rate for breast cancer was higher than that in the previous studies. Relationships between characteristics and prognosis of breast cancer were consistent with the previous findings.

Epstein-Barr virus-associated gastric cancer: A distinct subtype.

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a common malignant tumor associated with EBV infection. The molecular classification of gastric carcinoma indicates that EBVaGC is a distinct subtype in terms of oncogenesis and molecular features. Viral proteins, Bam-HI-A rightward transcripts (BART) miRNAs, and Bam-HI A rightward frame 1 (BARF1) promote oncogenesis after EBV infection via the induction of methylation, regulation of host gene expression, and malignant transformation. Together with abnormal mutations and amplification of the host genome as driving factors, interactions between the EBV genome and host genome accelerate carcinogenesis. The molecular profile of EBVaGC is that of EBV driving DNA hypermethylation, frequent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations, and the overexpression of Janus kinase 2 (JAK2), programmed death ligand-1 (PD-L1), and PD-L2. Clinically, the frequency of lymph node metastasis is lower, and the prognosis is better for EBVaGC than EBV-negative gastric cancer (EBVnGC). Pathologically, EBVaGC is a gastric adenocarcinoma with lymphoid stroma. This review interprets how the EBV genome is involved in the oncogenesis of gastric cancer and describes the molecular and clinicopathological features of EBVaGC.

An analysis of preoperative shoulder and neck balance and surgical outcome in 111 adolescent idiopathic scoliosis patients with two subtypes of Lenke 1 curves.

The incidence of postoperative shoulder imbalance following posterior spinal fusion (PSF) is still high in Lenke 1 curves despite following current treatment recommendations for upper instrumented vertebra (UIV) selection. The objective of this retrospective study was to identify differences in preoperative shoulder balance and to report the surgical outcome of two subtypes of Lenke 1 curves (flexible vs stiff) in patients with adolescent idiopathic scoliosis (AIS). The authors grouped patients' curves as Lenke 1-ve (flexible) when their preoperative proximal thoracic side bending (PTSB) Cobb angle was < 15° and as Lenke 1+ve (stiff) when the PTSB Cobb angle was 15°-24.9°. The authors hypothesized that these two subtypes had distinct preoperative and postoperative shoulder and neck balance following PSF using pedicle screw constructs. Fifty patients had Lenke 1 (flexible) curves and 61 had Lenke 1 (stiff) curves. The mean preoperative T1 tilt for patients with Lenke 1 (flexible) was -4.9° ± 5.3°, and for those with Lenke 1 (stiff) curves it was -1.0° ± 5.3° (p < 0.001). Mean cervical axis (CA) was -0.1° ± 3.2° for Lenke 1 (flexible) curves and 2.3° ± 3.5° for Lenke 1 (stiff) curves (p < 0.001). Preoperative radiographic shoulder height (RSH) and clavicle angle (Cla-A) were similar between the two curve subtypes. Following surgery, there were significant differences between the subtypes in terms of T1 tilt (p < 0.001), RSH (p = 0.014), and Cla-A (p = 0.031). Interestingly, 41.0% of patients with a Lenke 1 (stiff) curve had +ve T1 tilt compared to 2.0% in Lenke 1 (flexible) group. Moreover, 26.2% of patients with the Lenke 1 (stiff) curve had +ve RSH compared to 12.0% of those with Lenke 1 (flexible) curves. And, 24.6% of patients with Lenke 1 (stiff) had +ve Cla-A compared to 10.0% of those with Lenke 1 (flexible) curves. Lenke 1 (flexible) and Lenke 1 (stiff) curves had distinct preoperative T1 tilt and CA measurements. Following PSF, the authors noted +ve T1 tilt in 41% of patients with Lenke 1 (stiff) curves versus 2.0% in those with Lenke 1 (flexible) curves. The authors also noted a significant difference in postoperative RSH and Cla-A measurements.

0522 Subtypes of Insomniacs Treated by Cognitive-Behavioral Therapy

Abstract Introduction Insomnia disorder (ID) is characterized by high degree of heterogeneity. Aim of our study was to identify ID patients subtypes in terms of sleep and non-sleep clinical baseline (BL) features and CBT-I efficacy. Methods 294 chronic insomnia patients (61.6% female, mean age 40.7 ± 12.3 yrs) underwent 7-sessions group CBT-I. By use of latent class analysis (LCA) we identified ID subtypes according to BL score of Glasgow Sleep Effort Scale (GSES); Epworth Sleepiness Scale (ESS); Dysfunctional Beliefs and Attitudes about Sleep (DBAS -16); Morningness-Eveningness Questionnaire Self-Assessment (MEQ-SA); Perceived Stress Scale (PSS); Profile of Mood States (POMS); Beck Depression Inventory (BDI-II); Stay-Trait Anxiety Inventory (STAI-Y); Treatment effectiveness (Delta score of Insomnia Severity Index ISI between BL and end-of-treatment). Results We chose 3 latent classes as most parsimonious model. According to questionnaires’ cut-off, we labeled three classes: Class 1 (insomnia+anxiety+depression+stress) (n=62), Class 2 (insomnia+anxiety+depression) (n=153), Class 3 (only insomnia) (n=79). The variables that best differentiate the 3 classes were POMS (.772), STAY (.660), PSS (.545), BDI (.406) and ISI (.228) at BL. In particular, for ISI, the best item predicting groups differentiation was item 3 on the impact of insomnia on daytime functioning (.224). Moreover, we found a significant interaction between CBT-I treatment effect and the 3 classes at the ISI score (p=.001), GSES score (p=.002), DBAS score (p&amp;lt;.05), PSS score (p&amp;lt;.001), POMS score (p&amp;lt;.001), BDI score (p&amp;lt;.001) and STAI-Y score (p&amp;lt;.001). Conclusion Our data driven analysis results suggest that the heterogeneity of ID patients can be best represented by non-sleep scores, in particular those regarding depression, anxiety, stress and daytime functioning. These information can be useful in predicting the outcome of CBT-I. Support No

MP28-18 DISSECTING THE TRANSCRIPTOME LANDSCAPE OF MOUSE BLADDER UROTHELIUM BY SINGLE-CELL RNA-SEQ ANALYSIS

INTRODUCTION AND OBJECTIVE:Much of the information to date in terms of subtypes and function of bladder urothelial cells were derived from anatomical location or by the expression of a small number...

Skip N2 Metastasis in Pulmonary Adenocarcinoma: Good Prognosis Similar to N1 Disease

IntroductionThe prognostic effect and mechanism of skip N2 lung cancer remain unclear. Our study aimed to elucidate the influence of skip N2 on overall survival (OS) and disease-free survival (DFS) compared with N1 and non-skip N2 in patients with lung adenocarcinoma. Patients and MethodsPatients with lung adenocarcinoma and lymph node involvement between May 2011 and December 2015 were retrospectively analyzed. The outcomes of skip N2 patients were compared with N1 and non-skip N2 patients. Prognosis was further investigated according to the N status in different adenocarcinoma subtypes. Univariate and multivariate analyses were carried out to define independent risk factors for OS and DFS. ResultsA total of 456 patients with lung adenocarcinoma, 169 with N1 disease, 81 with skip N2 disease, and 206 with non-skip N2 disease, were enrolled in this study. All tumors were invasive adenocarcinoma, and the predominant subtypes were acinar in 252, papillary in 42, solid in 119, micropapillary in 20, and invasive mucinous adenocarcinoma in 23 patients. The DFS and OS of N1 and skip N2 diseases were similar and significantly better than those of patients with non-skip N2 disease. The prognosis according to lymph node status was significantly different in acinar-predominant subtypes in terms of both OS and DFS. ConclusionsSkip N2 disease has a similar prognosis to N1 disease and is significantly better than that of non-skip N2 disease in relation to OS and DFS. Skip N2 has a prognostic advantage in patients with the acinar-predominant subtype.

Trends in lung cancer incidence within the last 10 years: An Eastern Anatolian single center experience

Aim: Lung cancer is the most common cause of cancer-related deaths among men and women, and mortality and morbidity rates vary according to different histological groups. Therefore, histological type determination is extremely important. The purpose of the study is to investigate the histological subtypes of lung cancer cases within the last 10 years in one of the biggest centers of the Eastern Anatolian Region, considering the changes made in the 2015 updates in lung tumors by World Health Organization (WHO), and investigate the relationship between these histological sub-types and distribution according to year, gender and age. Methods: In this cross-sectional study, patients who were referred for lung biopsy between January 2010 and December 2019 and diagnosed with lung carcinoma were retrospectively analyzed. Results: Our study shows that the frequency of lung cancer, along with histological subtypes, has increased throughout the years. The most common lung cancer type, regardless of gender, is Squamous Cell Carcinoma (SCC), followed by Small Cell Lung Carcinoma (SCLC) and Adenocarcinoma. Adenocarcinoma and SHC were the most common subtypes among females and males, respectively. A significant relationship was observed between gender and histological type (P&lt;0.001).Conclusion: The data from our study suggest that the incidence of lung cancer increased throughout the years, similar to the data from our country and other developing countries around the world. In terms of subtypes, among developing countries, Adenocarcinoma rate increased while SCC rate decreased. In our study, the most common histological types increased at a similar rate. Adenocarcinoma was the most common lung cancer among females, similar to other developing countries. The most common lung cancer overall remained the same: SCC. This was considered an indication of the unchanged smoking habits of males.

Prognostic significance of the sub-classification of stage pT3a renal tumors by perinephric and sinus fat invasion.

In the current Tumor-Node-Metastasis (TNM) classification system for renal cell carcinoma (RCC), both perinephric fat invasion (PFI) and renal sinus fat invasion (SFI) are classified at the T3a stage. However, their associated prognoses are clinically controversial. The present study proposes a new sub-classification criterion for pathological T3a (pT3a) RCC with SFI or PFI to resolve this dispute. Data were collected from consecutive records of 2,765 patients with T1a renal cancer, who had undergone partial nephrectomy (PN) between 2001 and 2015 at one of four hospitals. Among these patients, 127 cases were diagnosed with stage pT3a RCC with SFI or PFI, according to final pathological examination. The pathological characteristics, clinical data and follow-up observations were analyzed. Of the 127 patients, with an average follow-up duration of 56 months (range, 15–60 months), 17 cases of tumor recurrence were found. After analysis of the pathological findings, the following new sub-classification criteria was proposed for pT3a RCC with SFI or PFI: i) Type A, renal tumor invades the pseudo-capsule and contacts with the perinephric adipose tissues directly (3 recurrences out of 57 patients); ii) type B, tumor protrudes into the perinephric adipose tissues like a tongue (4 recurrences out of 29 patients); and iii) type C, tumor nodules distribute in perinephric adipose tissues (10 recurrences out of 41 patients). There was statistically significant difference between the three subtypes in terms of recurrence rate (P=0.023). In conclusion, controversies remain in the current TNM classification system for pT3a RCC. The present study added to the available data and found that pT3a RCC with tumor nodules in perinephric adipose or/and with an irregular tumor protruding into adipose tissues showed a higher recurrence rate. Thus, it is recommended that pT3a RCC should be carefully analyzed and should be considered differently to other stages of RCC.

A topological approach for cancer subtyping from gene expression data.

Gene expression data contains key information which can be used for subtyping cancer patients. However, computational methods suffer from 'curse of dimensionality' due to very high dimensionality of omics data and therefore are not able to clearly distinguish between the discovered subtypes in terms of separation of survival plots. To address this we propose a framework based on Topological Mapper algorithm. The novelty of this work is that we suggest a method for defining the filter function on which the mapper algorithm heavily depends. Survival analysis of the discovered cancer subtypes is carried out and evaluated in terms of minimum pairwise separation between the Kaplan-Meier plots. Furthermore, we present a method to measure the separation between the discovered subtypes based on hazard ratios. Five cancer genomics datasets obtained from The Cancer Genome Atlas portal have been used for comparisons with Robust Sparse Correlation-Otrimle (RSC-Otrimle) algorithm and Similarity Network Fusion(SNF). Comparisons show that the minimum pairwise life expectancy difference (in days) between the discovered subtypes for lung, colon, breast, glioblastoma and kidney cancers is 107, 204, 20, 88 and 425days, respectively, for the proposed methodology whereas it is only 69, 43, 6, 61 and 282days for RSC-Otrimle and 9, 95, 18, 60 and 148days for SNF. Hazard ratio analysis also shows that the proposed methodology performs better in four of the five datasets. A visual inspection of Kaplan-Meier plots reveals that the proposed methodology achieves lesser overlap in Kaplan-Meier plots especially for lung, breast and kidney cases. Furthermore, relevant genetic pathways for each subtype have been obtained and pathways which can be possible targets for treatment have been discussed. The significance of this work lies in individualized understanding of cancer from patient to patient which is the backbone of Precision Medicine.

Fluorescent Polysaccharide Nanogels for the Detection of Tumor Heterogeneity in Drug-Surviving Cancer Cells.

Tumor metastasis, recurrence, and drug resistance have been associated with tumor heterogeneity, and thus the identification of tumor heterogeneity has great significance in medicine. The approach provides a way to identify and isolate various cell subtypes from drug-surviving ovarian cancer cells, by synthesizing a series of polysaccharide nanogels and using them in flow cytometry analysis. The results show that the drug-surviving OVCAR-3 cells that are subjected to paclitaxel intervention comprise various cell subtypes, including drug-resistant and non-drug-resistant cell subtypes. Besides, there are significant differences between the drug-resistant cell subtype and non-drug-resistant cell subtype in terms of their migration and invasion behavior. In addition, the phenotype switch genes are detected by mRNA sequencing, and it is found that different subtypes show significant genetic differences with regard to their drug resistance, metastasis, and proliferation. In particular, modifying polysaccharide nanogels with lipids can promote the uptake of nanogels by drug-resistant cells, and thus the lipid modification can enhance the effectiveness of a chemotherapy drug carrier against drug-resistant cells. These studies reveal the heterogeneity of drug-surviving tumor cells, as well as the significant differences in drug-resistance, migration, and invasion capabilities of different subtypes, and demonstrate a way to overcome drug resistance.