Subtype Pattern Research Articles

Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition.

Among central nervous system-associated malignancies, glioblastoma (GBM) is the most common and has the highest mortality rate. The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide. In precision medicine, research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity, as well as the refractory nature of GBM toward therapy. Deep understanding of the different molecular expression patterns of GBM subtypes is critical. Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes. The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors. These subtypes also exhibit high plasticity in their regulatory pathways, oncogene expression, tumor microenvironment alterations, and differential responses to standard therapy. Herein, we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype. Furthermore, we review the mesenchymal transition mechanisms of GBM under various regulators.

Abstract PO5-16-07: Unveiling the Landscape of PD-L1 Expression and Tumor-Infiltrating Lymphocyte Subtypes in Advanced Triple-Negative Breast Cancer

Abstract Background: Triple-negative breast cancer (TNBC) is known for its aggressive behavior with poor survival outcomes. Influenced by different expression levels of Programmed Death-Ligand 1 (PD-L1) and several subtypes of tumor-infiltrating lymphocytes (TILs), tumor microenvironment (TME) plays a crucial role in TNBC response to treatment and progression. Objective: To assess the prevalence and prognostic role of PD-L1 expression in advanced TNBC, defined as unresectable stage III or stage IV disease, in patients treated with a standard cytotoxic chemotherapy regimen. TILs composition was also evaluated as an exploratory objective. Methods: The internal database of the Brazilian National Cancer Institute was queried out for women diagnosed and treated with advanced TNBC from January 2018 to December 2022. Formalin-fixed paraffin-embedded samples of a maximum of four years old were analyzed. PD-L1 expression using 22C3 pharmDX assay was estimated through combined positive score (CPS) dichotomization (CPS < 10 vs. CPS≥10). Tissue microarrays comprising the samples of biopsies were subjected to immunohistochemistry, targeting specific markers including CD3, CD4, CD8, CD56, CD68, CD117, FOXP3, PD-1, the immune cell profiles were carefully examined and their correlation with the PD-L1 CPS was determined. Results: A total of 150 patients were included. The expression of PD-L1 was undetermined in 2 cases. The median age was 51.5 years (IQR 41.8-60.2) and 20.9% of the cases had CPS≥10. Most patients were < 65 years (73.0%), were postmenopausal (56.8%) and belonged to non-white ethnicity (70.3%). Postmenopausal women predominated in the CPS≥10 subgroup (74.2%) (Table 1). No significant differences in demographic characteristics and clinicopathological variables were observed based on PD-L1 subgroups, 117 patients (79.1%) had CPS < 10, with 91 (77.8%) being de novo stage IV metastatic disease. CD3+ (p=0.037), CD4+ (p=0.005) and CD8+ (p=0.001) TILs had higher expression in tumors with PD-L1 CPS≥10 (Table 2). According to the treatment received, almost half of the patients only received first-line chemotherapy (47%), as the following second line was applied to 28.8% of the total group. The third and fourth lines were administered in 12.9% and 9.1% of patients, respectively. Only 2 patients went through five palliative chemotherapy lines, and only one received up to 6 treatment lines. Between the subgroups CPS≥10 versus CPS < 10 no statistically significant differences were observed in the median progression-free survival (PFS) (5.1 vs. 5.0 months, p=0.89) and overall survival (OS) (8.7 vs. 8.8 months, p=0.6). Conclusion: This study offers insights into the expression patterns of PD-L1 and TILs subtypes in advanced TNBC cases in Brazil. PD-L1 CPS did not influence survival outcomes for this cohort of patients treated with cytotoxic chemotherapy only. The composition of TILs subtypes within the TME appears to vary based on PD-L1 CPS. Table 1. Advanced TNBC population characteristic by CPS (Nf148). Table 2. Tumor Infiltrating Lymphocytes characterization (CD3, CD4, CD8, CD56, CD68, CD 117, FOXP3 and PD-1) and its correlation with CPS status. Citation Format: Alexssandra Lima Siqueira dos Santos, Jesse Lopes da Silva, Lucas Zanetti de Albuquerque, Antônio Lucas Araújo Neto, Cecília Ferreira da Silva, Luana Aguiar Mesquita Cerva, Isabele Ávila Small, Cicera Pimenta Marcelino, Paula de Mendonça Batista, Maria Aparecida do Carmo Rego, Maria Amélia Carlos Souto Maior Borba, Andreia Cristina de Melo. Unveiling the Landscape of PD-L1 Expression and Tumor-Infiltrating Lymphocyte Subtypes in Advanced Triple-Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-07.

Dermoscopy of Actinic Lichen Planus in Skin of Color.

Actinic Lichen Planus (ALP) is a rare photosensitive variant of lichen planus. Four subtypes can be distinguished: pigmented, annular (AALP), plaque-like and dyschromic ALP. This is a retrospective; descriptive and analytical study investigating the dermoscopic patterns of different subtypes of ALP in skin of color. Sixteen adult patients were included in this study; the majority of them were young females, while five patients with the pigmented subtype of ALP were more than 50 years old. This subtype was more prevalent in patients with phototype IV. AALP was described in men with a very dark phototype.In pigmented melasma-like ALP, dermoscopy showed an annular granular pattern, white reticular and circular Wickham striae (WS) with hypopigmentation lacking skin creases, dots inside circles and an eccentric pigmentation on circles. In ALP, annular, circular WS; and perifollicular white halos with follicular plugs were described. The black hole pattern with dotted vessels was seen in the dyschromic ALP. White-yellow-bluish WS were noticed in plaque-type ALP with circumferential radial lines at the periphery. This descriptive study of dermoscopic patterns of various subtypes of ALP in skin of color highlighted new dermoscopic descriptions that vary according to the clinical variant or the morphology; lesions distribution; and phototype. Also, many epidemiological differences were found between our results and the literature concerning the older age of onset in melasma-like pigmented ALP, and the male predominance in annular ALP.

Can 18 F FDG PET/CT metabolic parameters be used to noninvasively differentiate between different histopathological subtypes and Fuhrman grades of renal cell cancer?

To evaluate relationship between metabolic PET metabolic parameters and size of the primary tumor, various histopathological subtypes of renal cell carcinoma (RCC) and Fuhrman grade of the tumors. Retrospective analysis of 93 biopsy-proven RCC patients who underwent pretreatment flourine 18 flourodeoxyglucose PET/computed tomography ( 18 F FDG PET/CT) was performed. Quantitative PET parameters, size of the primary tumor, histopathological subtypes and Fuhrman grades of the tumor were extracted. We tried to assess if there was any significant difference in the metabolic patterns of various histopathological subtypes of RCCs, Fuhrman grade of the tumors and size of the primary tumor. A significant correlation was noted between the size of primary tumor and maximum standardized uptake value (SUV max ), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) ( P < 0.01, P < 0.001 and P < 0.001, respectively). SUV max values correlated significantly with the histopathological subtype ( P < 0.001). Further sub-analyses was also done by segregating the patients into Low grade (Fuhrman grade 1 and 2) vs. High grade (Fuhrman grade 3 and 4). SUV max , MTV and TLG were significantly different between high grade vs. low grade tumors. ROC analysis yielded cut off values for SUV max , MTV and TLG to differentiate between high grade from low grade tumors. FDG PET/CT with the use of metabolic PET parameters can differentiate between different histopathological subtypes of RCC. Incorporation of metabolic parameters into clinical practice can potentially noninvasively identify patients with low-grade vs. high-grade RCC.

Tubulin alpha-1b chain was identified as a prognosis and immune biomarker in pan-cancer combing with experimental validation in breast cancer

The α-tubulin subtype, Tubulin α-1b chain (TUBA1B), has been shown to influence immune cell infiltration, cancer growth, and survival across various malignancies. However, a comprehensive study has not yet been undertaken examining the immunological and predictive effects of TUBA1B in a pan-carcinoma context. Using data from TCGA, GEO, and other databases, we analyzed TUBA1B expression across various carcinoma types using transcriptional profiling, prognostic implications, genetic and epigenetic alterations, methylation patterns, and immunological significance. To validate our findings, we conducted Western blot analysis to assess TUBA1B protein levels in matched breast cancer tissue samples and performed CCK-8 proliferation assay, flow cytometry, transwell invasion, and migration assays to comprehensively examine the functional impact of TUBA1B on breast cancer cells. Our pan-cancer analysis found TUBA1B upregulation across most tumor types, with varying expression patterns in distinct immune and molecular subtypes. High TUBA1B expression was an independent risk factor and associated with poor prognoses in several cancers, including BRCA, KICH, LGG, LUAD, and MESO. TUBA1B also demonstrates moderate to high diagnostic accuracy in most tumor types. Increased m6A methylation levels were observed in the TUBA1B gene, while its promoter region displayed low methylation levels. TUBA1B's expression impacted some cancers by elevating tumor mutation burden, microsatellite instability, neoantigen formation, immune cell infiltration, and the modulation of immune checkpoints. Functional enrichment analysis highlights TUBA1B’s involvement in important cellular processes such as the cell cycle, p53 signaling, cell senescence, programmed cell death, and the regulation of immune-related pathways. Moreover, our study reveals higher TUBA1B protein expression in breast cancer tissues compared to adjacent tissues. In vitro experiments confirm that TUBA1B deletion reduces breast cancer cell proliferation, invasion, and migration while increasing apoptosis. In conclusion, our study suggests that TUBA1B could potentially serve as a diagnostic marker for predicting cancer immunological profiles and survival outcomes and shed light on the expression and role of TUBA1B in breast cancer, providing a solid foundation for considering it as a promising therapeutic target for breast cancer patient treatment.

Effect of Myelin Debris on the Phenotypic Transformation of Astrocytes after Spinal Cord Injury in Rats

After spinal cord injury (SCI), the accumulation of myelin debris can serve as proinflammatory agents, hindering axon regrowth and exacerbating damage. While astrocytes have been implicated in the phagocytosis of myelin debris, the impact of this process on the phenotypic transformation of astrocytes and their characteristics following SCI in rats is not well understood. Here, we demonstrated that the conditioned medium of myelin debris can trigger apoptosis in rat primary astrocytes in vitro. Using a compressional SCI model in rats, we observed that astrocytes can engulf myelin debris through ATP-binding cassette transporter sub-family A member 1 (ABCA1), and these engulfed cells tend to transform into A1 astrocytes, as indicated by C3 expression. At 4 days post-injury (dpi), astrocytes rapidly transitioned into A1 astrocytes and maintained this phenotype from 4 to 28 dpi, while A2 astrocytes, characterized by S100, were only detected at 14 and 28 dpi. Reactive astrocytes, identified by Nestin, emerged at 4 and 7 dpi, whereas scar-forming astrocytes, marked by N-cadherin, were evident at 14 and 28 dpi. This study illustrates the distribution patterns of astrocyte subtypes and the potential interplay between astrocytes and myelin debris after SCI in rats. We emphasize that myelin debris can induce astrocyte apoptosis in vitro and promote the transformation of astrocytes into A1 astrocytes in vivo. These two classification methods are not mutually exclusive, but rather complementary.

Immunohistochemical and Clinicopathologic Profiling of Pituitary Adenomas at a Nigerian Tertiary Hospital

Background: Pituitary adenoma is the most common pituitary tumour and the third most common intracranial tumour worldwide. Only a few studies have been done in Africa on the immunohistochemical expression pattern and clinicopathologic presentations of the different hormonal subtypes of pituitary adenomas. Objective: To evaluate the immunohistochemical hormonal profiles and clinicopathologic behaviour of pituitary adenomas diagnosed within ten years at the Lagos University Teaching Hospital, Lagos, Nigeria. Methods: In this 10-year retrospective, cross-sectional study, all cases of pituitary adenomas diagnosed at the hospital mentioned above between 1 January 2009 and 31 December 2018 were analysed. Their paraffin-embedded tissue blocks were stained with haematoxylin and eosin and then with immunostains for growth hormome (GH), adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH), follicular stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL), using their standard immunohistochemistry protocols. Results: Seventy pituitary adenoma cases were studied. The male-to-female ratio of the patients was 1.6:1. The median age was 45 years, and the peak age of occurrence was the fifth decade for both sexes. Most were null cell adenomas (44.7%) and FSH-beta gonadotrophs (22.9%). The least diagnosed were thyrotroph (1.4%) and corticotroph adenomas (1.4%). Most of the adenomas were macroadenomas, and the most common presenting symptom was visual impairment. Conclusion: Pituitary adenoma is commoner in males in their 5th decade of life at the Lagos University Teaching Hospital, Lagos, Nigeria. The null cell adenoma is the commonest type of pituitary adenoma diagnosed in the center, and the majority of the patient diagnosed with pituitary adenoma present late with complications of visual impairment.

Time of the day and season distribution among stroke code subtypes: differences between ischemic stroke, intracranial hemorrhage, and stroke mimic.

Circadian variations in the timing of the onset of stroke symptoms have been described, showing a morning excess of cardiovascular risk. To date, no differences have been found between stroke subtype and time distribution throughout the day. The present study aims to compare the seasonal and circadian rhythm of symptoms onset in ischemic, hemorrhagic, and stroke mimic patients. This study was conducted prospectively at a hospital and involved a cohort of stroke alert patients from 2018 to 2021. Stroke subtypes were classified as ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack (TIA), and stroke mimic. Clinical variables were recorded, and each patient was assigned to a 4-h interval of the day according to the time of onset of symptoms; unwitnessed stroke patients were analyzed separately. Seasonal changes in stroke distribution were analyzed at 3-month intervals. A total of 2,348 patients were included in this analysis (ischemic 67%, ICH 13%, mimic 16%, and TIA 3%). Regardless of stroke subtype, most of the patients were distributed between 08-12 h and 12-16 h. Significant differences were found in the time distribution depending on stroke subtype, with ICH predominating in the 4-8 h period (dawn), most of which were hypertensive, TIA in the 12-16 h period (afternoon), and stroke mimic in the 20 h period (evening). The ischemic stroke was evenly distributed throughout the different periods of the day. There were no differences in the seasonal pattern between different stroke subtypes, with winter being the one that accumulated the most cases. The present study showed different circadian patterns of stroke subtypes, with a predominance of ICH at dawn and stroke mimic in the afternoon. The stroke circadian rhythm resembles previous studies, with a higher incidence in the morning and a second peak in the afternoon.

Abstract 2265: Distinct alternative splicing patterns in genetic subtypes of diffuse large B-cell lymphoma

Abstract Advances in sequencing techniques have made molecular subgrouping of Diffuse Large B-cell Lymphoma (DLBCL) based on DNA cahnges, which has led to the development of Lymphgen classification. By the way, although alternative splicing (AS) in cancer cells contributes to proliferation, invasion and metastasis, and immune escape, their role and association with DLBCL molecular subtypes are unknown. Therefore, we analyzed whole-exome sequencing (WES) and bulk RNA-Seq data paired in the public EGA dataset (EGAD00001003600) to explore the patterns of AS events that differ between Lymphgene subtypes. The WES data of 620 DLBCL samples that passed quality control were aligned to the reference using BWA-MEM, and variants were called with Mutect2. We used the information of copy number variants provided by cBioPortal. The RNA-Seq analysis was performed using the STAR-RSEM pipeline and differential splicing events were detected using rMATS to compare subtypes. Among 620 DLBCL samples, there were 19 MCDs, 95 EZBs, 22 BN2s, and 137 ST2s (50 samples with multiple genetic classes, and 291 samples unclassified). Mutations in spliceosome complex genes (ZRSR2 and SF1) were found in 14 and 27 samples, respectively. In BN2 and MCD subtypes, splicing events with significantly different exon inclusion levels were observed at a high frequency of 29 and 16 occurrences, respectively, compared to other subtypes. (P-value &amp;lt; 0.05). In contrast, retained intron is the only event observed in the EZB subtype (Table 1). Samples with mutations in ZRSR2 and SF1 showed four and two aberrant events, respectively, compared to samples without these mutations. Of note, rMATS detected an alternative 3’ splice site event in exon 6 of CD37 in the MCD. CD37 is involved in tumorigenesis in leukocytes and has been suggested as a potential biomarker in blood cancer, and its dysregulation may have influenced the poor prognosis of MCD. In summary, molecular subtypes of DLBCL had unique features in terms of alternative splicing. Functional consequences of these selective exon usages for each DLBCL subtype are being warranted. Citation Format: Sanyeowool An, Youngil Koh, Sung-Soo Yoon. Distinct alternative splicing patterns in genetic subtypes of diffuse large B-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2265.

Abstract 5673: Transposable element expression patterns in epigenetic mutational subtypes of clear cell renal cell carcinoma

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is characterized by mutations in epigenetic modulators and by aberrant transposable element (TE) expression, each of which have been separately associated with immunotherapy (IO) benefit in specific clinical contexts. However, the relationship between mutations in epigenetic regulators and TE expression, and the potential effect of both somatic mutations and TE expression on clinical outcomes, has not been fully investigated. Methods: We utilized RNA sequencing from ccRCC patients’ tumors and cell lines to quantify TE subfamily expression with TEtranscripts (n=123 metastatic IO-treated; CheckMate-009, 010, 025, n=355 all stage TCGA untreated, n=8 CCLE). Locus-specific endogenous retrovirus (ERV) expression was quantified using hervQuant. Differential TE and ERV expression was determined using DESeq2. Samples were stratified by mutations in PBRM1, SETD2, BAP1 and KDM5C, four of the top five mutated genes in ccRCC. Multivariable CoxPH models and the log-rank test were used to compare overall (OS) and progression-free survival (PFS). Two validation metastatic ccRCC cohorts were employed: the everolimus arm of CheckMate-025 (n=78, CM025e) and IMmotion150 (n=146, IM150). Results: Global TE expression (LTR, LINE, SINE and DNA transposons) did not differ significantly across mutational and clinical subtypes. However, 29 of 795 TE subfamilies were differentially expressed in &amp;gt;1 mutational subtype across datasets, and 22 of 29 were ERVs. At locus-specific resolution, 52 of 3173 ERVs were differentially expressed in &amp;gt;1 mutational subtype across datasets. Additionally, 6 of the 52 ERVs nominally associated with PFS, and 4 nominally associated with OS, in the IO cohort. Among them, only ERVs 544 and 2014 associated with improved PFS (multivariable CoxPH p = 0.03 and 0.02, respectively) and were expressed across all datasets. Both ERVs also exhibited increased expression in PBRM1 mutant and decreased expression in BAP1 mutant vs. wildtype samples, in discovery (IO, TCGA, CCLE) and validation (CM025e, IM150) cohorts. Lastly, PBRM1 mutant patients with high ERV 544 or 2014 expression had improved PFS in the IO (log-rank p = 0.04 and 0.03, multivariable CoxPH p = 0.008 and 0.009, respectively, HR = 0.43 both), but not in the CM025e cohort, compared to other patients regardless of PBRM1 mutations. Conclusion: ERVs 544 and 2014 were upregulated in PBRM1 mutant and downregulated in BAP1 mutant samples. Coupled with PBRM1 inactivation, their expression served as a candidate biomarker of improved PFS in IO-treated ccRCC that may have additional biological relevance. Expanded functional and clinicogenomic studies of epigenetic mutational subtype-specific patterns of TE expression, and their relation to selective IO response, may guide additional discovery and therapeutic development strategies in ccRCC. Citation Format: Kevin Meli, Cora A. Ricker, Sabrina Y. Camp, Christof C. Smith, Chris Labaki, Eddy Saad, Hanna Soulati, Brendan Reardon, Jihye Park, Natalie I. Vokes, Benjamin G. Vincent, Toni K. Choueiri, David A. Braun, Eliezer M. Van Allen. Transposable element expression patterns in epigenetic mutational subtypes of clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5673.

Incidence trends for common subtypes of T-cell lymphoma in Taiwan and the United States from 2008-2020.

The incidence of T-cell lymphoma (TCL) has been continually increasing in Taiwan and the United States (US) in recent years. This epidemiological study using population-based registry data aimed to determine the incidence patterns of common subtypes of TCL in Taiwan from 2008-2020 and compare them with those in the US and the Asian/Pacific Islander (API) population. Subtypes included angioimmunoblastic T-cell lymphoma (AITL); extranodal NK/T-cell lymphoma, nasal or other type (ENKTL); peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); and anaplastic large cell lymphoma (ALCL). The total number of patients newly diagnosed with TCL during 2008-2020 was 4477, 3171, and 48,889 in Taiwan, API, and the US, respectively. Except the incidence rate of AITL in Taiwan, the incidence rates of these common TCL subtypes showed downward trends in all studied populations. There was also a significant increase in the relative frequency of AITL among TCL in Taiwan, with an annual percent change of 4.44 (p < 0.001), from 8.44% in 2002 to 20.63% in 2020. The rapid development of diagnostics may be the main factor contributing to this rise in incidence.

Heterogeneity of molecular subtyping and therapy-related marker expression in primary tumors and paired lymph node metastases of small cell lung cancer.

The classification of molecular subtypes and the identification of targetable molecules have been proposed for small cell lung cancer (SCLC) patients. Our aim was to investigate whether the expression of these markers evaluated using lymph node (LN) metastases represents that of primary tumors. We enrolled 46 surgically resected SCLC patients' primary tumors and paired mediastinal LN metastases. The protein expression of subtype-defining markers (ASCL1, NEUROD1, POU2F3, and YAP1) and therapeutic markers (DLL3, MYC, PD-L1, and MHC I) was examined by immunohistochemistry and was correlated with clinicopathological parameters and prognoses. In primary and metastatic tumors, the expression of these markers was 78.3% and 87.0%, 50.0% and 63.0%, 13.0% and 6.5%, 17.4% and 15.2%, 84.8% and 87.0%, 17.4% and 6.5%, 50.0% and 34.8%, and 60.9% and 37.0%, respectively. Positive tumor PD-L1 expression was less present in LN metastases (p = 0.015), and the same was true for MHC I expression (p = 0.036). NEUROD1 and DLL3 expression levels in metastatic tumors were stronger (p < 0.001 and p = 0.002, respectively); conversely, POU2F3, MYC, PD-L1, and MHC I expression levels were weaker (p = 0.018, p = 0.019, p = 0.001, and p < 0.001, respectively). In 15 (32.6%) patients, we observed a change in the molecular subtyping pattern, and a higher number of neuroendocrine (NE)-high phenotype patients were diagnosed when using the LN specimens (91.3% vs. 84.8%). TNM stage and postoperative chemotherapy were independent prognostic factors in surgically resected SCLC patients, and no prognostic differences were found among molecular subtypes. This study highlights the discordance of subtype-specific proteins and therapeutic markers between SCLC primary tumors and LN metastases. Additionally, our findings have therapeutic and prognostic implications and warrant further clinical investigation.

ADAMTS Gene-Derived circRNA Molecules in Non-Small-Cell Lung Cancer: Expression Profiling, Clinical Correlations and Survival Analysis.

The present study examines the relationship between circular RNA (circRNA) derived from three genes of the family a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs): ADAMTS6, ADAMTS9 and ADAMTS12 and the host gene expression in non-small-cell lung cancer (NSCLC) with regard to various clinical factors. Notably, an association was identified between ADAMTS12 expression and specific circRNA molecules, as well as certain expression patterns of ADAMTS6 and its derived circRNA that were specific to histopathological subtypes. The survival analysis demonstrated that a lower ADAMTS6 expression in squamous cell carcinoma was associated with extended survival. Furthermore, the higher ADAMTS9 expression was linked to prolonged survival, while the overexpression of ADAMTS12 was correlated with a shorter survival. These findings suggest that circRNA molecules may serve as potential diagnostic or prognostic biomarkers for NSCLC, highlighting the importance of considering molecular patterns in distinct cancer subtypes.

Distinct Rates and Transmission Patterns of Major HIV-1 Subtypes among Men who Have Sex with Men in Guangxi, China.

The diversity and transmission patterns of major HIV-1 subtypes among MSM population in Guangxi remains unknown. Understanding the characteristics is crucial for effective intervention strategies. Between 2016 and 2021, we recruited individuals newly diagnosed with HIV-1 from MSM population in Guangxi. HIV-1 pol region was amplified and sequenced, and constructed molecular network, assessed clustering rate, cluster growth rate, spatial clustering, and calculating the basic reproductive number (R0) based on sequences data. We identified 16 prevalent HIV-1 subtypes among Guangxi MSM, with CRF07_BC (53.1%), CRF01_AE (26.23%), and CRF55_01B (12.96%) predominating. In the network, 618 individuals (66.17%) formed 59 clusters. Factors contributing to clustering included age < 30 years (AOR = 1.35), unmarried status (AOR = 1.67), CRF07_BC subtype (AOR = 3.21), and high viral load (AOR = 1.43). CRF07_BC had a higher likelihood of forming larger clusters and having higher degree than CRF01_AE and CRF55_01B. Notably, CRF07_BC has higher cluster growth rate and higher basic reproductive number than CRF01_AE and CRF55_01B. Our findings underscore CRF07_BC as a prominent driver of HIV-1 spread among Guangxi's MSM population, highlighting the viability of targeted interventions directed at specific subtypes and super clusters to control HIV-1 transmission within this population.

Glucocorticoid and Adrenergic Receptor Distribution Across Human Organs and Tissues: A Map for Stress Transduction.

Psychosocial stress is transduced into disease risk through energy-dependent release of hormones from the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary axes. The levels of glucocorticoid and adrenergic hormones, together with the sensitivity of tissues to their signaling, define stress responses. To understand existing pathways responsible for the psychobiological transduction of stressful experiences, we provide a quantitative whole-body map of glucocorticoid and adrenergic receptor (AR) expression. We systematically examined gene expression levels for the glucocorticoid receptor (GR), α- and β-ARs (AR-α1B, AR-α2B AR-β2, and AR-β3), across 55 different organs using the Human Protein Atlas and Human Proteome Map datasets. Given that mitochondria produce the energy required to respond to stress, we leveraged the Human Protein Atlas and MitoCarta3.0 data to examine the link between stress hormone receptor density and mitochondrial gene expression. Finally, we tested the functional interplay between GR activation and AR expression in human fibroblast cells. The GR was expressed ubiquitously across all investigated organ systems, whereas AR subtypes showed lower and more localized expression patterns. Receptor co-regulation, meaning the correlated gene expression of multiple stress hormone receptors, was found between GR and AR-α1B, as well as between AR-α1B and AR-α2B. In cultured human fibroblasts, activating the GR selectively increased AR-β2 and AR-α1B expression. Consistent with the known energetic cost of stress responses, GR and AR expressions were positively associated with the expression of specific mitochondrial pathways. Our results provide a cartography of GR and AR expression across the human body. Because stress-induced GR and AR signaling triggers energetically expensive cellular pathways involving energy-transforming mitochondria, the tissue-specific expression and co-expression patterns of hormone receptor subtypes may in part determine the resilience or vulnerability of different organ systems.

Electrophysiological variations of Guillain-Barre syndrome in Bangladesh- Hospital based study

Introduction: Guillain-Barre syndrome (GBS) is an immune mediated disorder of peripheral nerves which usually presents by rapidly evolving ascending weakness &amp; mild sensory loss and hypo- or areflexia. Electrodiagnostic study (EDS) is the basis for classification of different subtypes of the disease. EDS also has a crucial role in diagnosis, ruling out of some differential diagnosis like myopathic and motor neuron disorders and confirming the neuropathic nature of GBS. The benefit of immunotherapy is greatest when introduced early. In addition, electrophysiological characteristic can predict the prognosis of patients with GBS. This study was conducted to determine the predominant subtype and electrophysiological pattern of GBS in the context of Bangladesh. Objectives: Objective of this study was to compare the electrophysiological variations among different electrophysiological subtypes of GBS. Methods: It is an observational cross sectional study conducted in Department of Medicine and Neurology, Sir Salimullah Medical College &amp; Mitford Hospital and National Institute of Neuroscience (NINS), Dhaka, over a period of one year &amp; four months. Total 30 patients were selected by purposive sampling technique. Demographic data were collected from the patients and recorded in structured case report form. Clinical examination and relevant investigations were done meticulously. Collected questionnaire were checked to identify any error in data. Data was analyzed with SPSS version 21 software. Result: In this study, maximum numbers of patients 53% were between 21-30 years of age group with mean value 27.47±8.1 years. Male to female ratio was 1.7:1. Frequency of Guillain-Barre syndrome is predominance at middle age group. Commonest presentation was limb weakness (parapledgia or quadripledgia) in 60% patients, paresthesias &amp; numbness (40%), pain (100%) and deviation of mouth (63%) of GBS patients. Cerebrospinal fluid shows a mild pleocytosis (5 to 50 cells/µl) in majority of cases was found in 76% of patients. Whereas elevated CSF Protein (&gt;45 mg/dl) was seen in all GBS patient. Increased distal motor latency (DML) was found in 93% patients, whereas 7% patients had normal DML. In the case of the lower limbs, increased distal motor latency was predominant. Decreased amplitude of sensory nerve action potential (SNAP) was seen in 83% patients while 16% patients had normal. Slowing of motor conduction velocities, decreased amplitude as well as increase in distal motor latencies were observed, being more pronounced in the lower limbs. F-wave was completely absent in 20.0% patients while 20% patients showed decreased conduction velocity with prolonged latency. Sensory nerve action potential revealed that decreased sensory conduction velocity (SCV) was seen in 26%, absent SCV in 10% and normal SCV in 63% patients. Present study demonstrated that Acute inflammatory demyelinating polyneuropathy (AIDP) was the commonest type of Guillain-Barré syndrome, present in 56% of patient. Around 30% of the patients belonged to acute motor axonal polyneuropathy (AMAN) and 13% were acute motor sensory axonal polyneuropathy (AMSAN). Conclusion: In this study AIDP was the most frequent subtype. The characteristic findings supportive of AIDP include prolonged distal motor latencies, reduced conduction velocities, conduction blocks at non-entrapment sites, temporal dispersion and prolonged F wave latencies. J MEDICINE 2024; 25: 11-16

Value of altered methylation patterns of genes RANBP3, LCP2 and GRAP2 in cfDNA in breast cancer diagnosis.

The purpose of this study was to investigate the potential of plasma cfDNA methylation patterns in reflecting tumour methylation changes, focusing on three candidate sites, cg02469161, cg11528914, and cg20131654. These sites were selected for verification, with a particular emphasis on their association with breast cancer. We conducted a comprehensive analysis of 850k whole-methylation sequencing data to identify potential markers for breast cancer detection. Subsequently, we investigated the methylation status of the genes Ran-binding protein 3 (RANBP3), Lymphocyte cytoplasmic protein 2 (LCP2), and GRB2 related adaptor protein 2 (GRAP2), situated at the specified sites, using cancer and canceradjacent tissues from 17 breast cancer patients. We also examined the methylation patterns in different molecular subtypes and pathological grades of breast cancer. Additionally, we compared the methylation levels of these genes in plasma cfDNA to their performance in tissues. Our analysis revealed that RANBP3, LCP2, and GRAP2 genes exhibited significant methylation differences between cancer and cancer-adjacent tissues. In breast cancer, these genes displayed diagnostic efficiencies of 91.0%, 90.6%, and 92.2%, respectively. Notably, RANBP3 showed a tendency towards lower methylation in HR+ breast cancer, and LCP2 methylation was correlated with tumour malignancy. Importantly, the methylation levels of these three genes in plasma cfDNA closely mirrored their tissue counterparts, with diagnostic efficiencies of 83.3%, 83.9%, and 77.6% for RANBP3, LCP2, and GRAP2, respectively. Our findings propose that the genes RANBP3, LCP2, and GRAP2, located at the identified methylation sites, hold significant potential as molecular markers in blood for the supplementary diagnosis of breast cancer. This study lays the groundwork for a more in-depth investigation into the changes in gene methylation patterns in circulating free DNA (cfDNA) for the early detection not only of breast cancer but also for various other types of cancer.

Genetic Ancestry-specific Molecular and Survival Differences in Admixed Patients With Breast Cancer.

We aim to determine whether incremental changes in genetic ancestry percentages influence molecular and clinical outcome characteristics of breast cancer in an admixed population. Patients with breast cancer are predominantly characterized as "Black" or "White" based on self-identified race/ethnicity or arbitrary genetic ancestry cutoffs. This limits scientific discovery in populations that are admixed or of mixed race/ethnicity as they cannot be classified based on historical race/ethnicity boxes or genetic ancestry cutoffs. We used The Cancer Genome Atlas cohort and focused on genetically admixed patients that had less than 90% European, African, Asian, or Native American ancestry. Genetically admixed patients with breast cancer exhibited improved 10-year overall survival relative to those with >90% European ancestry. Within the luminal A subtype, patients with lower African ancestry had longer 10-year overall survival compared to those with higher African ancestry. The correlation of genetic ancestry with gene expression and DNA methylation in the admixed cohort revealed novel ancestry-specific intrinsic PAM50 subtype patterns. In luminal A tumors, genetic ancestry was correlated with both the expression and methylation of signaling genes, while in basal-like tumors, genetic ancestry was correlated with stemness genes. In addition, we took a machine-learning approach to estimate genetic ancestry from gene expression or DNA methylation and were able to accurately calculate ancestry values from a reduced set of 10 genes or 50 methylation sites that were specific for each molecular subtype. Our results suggest that incremental changes in genetic ancestry percentages result in ancestry-specific molecular differences even between well-established PAM50 subtypes which may influence disparities in breast cancer survival outcomes. Accounting for incremental changes in ancestry will be important in future research, prognostication, and risk stratification, particularly in ancestrally diverse populations.

Spectrum of Lymphomas involving Gastrointestinal tract in a Single Institution: A Retrospective Analysis

Abstract Introduction/Objective Lymphomas affecting the gastrointestinal (GI) tract are relatively uncommon occurrences. Given that GI biopsies are primarily evaluated by pathologists specializing in GI pathology, a comprehensive understanding of GI lymphomas is essential for accurate diagnosis and appropriate referral. However, there is limited updated studies of the prevalence and distribution of GI lymphoma subtypes in diverse patient populations. Therefore, the objective of this study was to address this knowledge gap by characterizing the prevalence and distribution patterns of GI lymphoma subtypes in a diverse patient population residing in the west coast region. Methods/Case Report A comprehensive retrospective review was conducted on patients diagnosed with lymphomas involving GI tract between 2015 and 2023 at a single institution over 8 years. Clinical and pathological data, including age, gender, tumor locations, and histological diagnoses, were collected and analyzed. Results (if a Case Study enter NA) A total of 32 cases diagnosed with lymphomas involving GI tract were included in this study. The patient population consisted of 44% female and 56% male, with an average age of 61 years (range: 35 to 93 years). The most common tumor locations (figure 1) were the stomach (53%), followed by the duodenum (16%), ileum and colon (8%). The other less frequent locations such as the pancreas, jejunum, and rectum and esophagus (each 3%). Notably, 38% (12 cases) of the total cases exhibited involvement of two or more anatomical sites. Conclusion Our study findings are consistent with previous literature, confirming that Diffuse Large B-cell Lymphoma (DLBCL) remains the most prevalent subtype of gastrointestinal (GI) lymphoma. The high frequency of stomach involvement aligns with the recognized association between Helicobacter pylori infection and lymphomagenesis. However, it is worth noting that the prevalence of MALT lymphoma has decreased, potentially indicating improved eradication efforts through antibiotic treatment. The observed proportion of cases with involvement of multiple anatomical sites highlights the diagnostic challenge of GI lymphomas and emphasizes the need for comprehensive evaluation.

Clinical features, imaging findings and molecular data of limb-girdle muscular dystrophies in a cohort of Chinese patients

BackgroundLimb-girdle muscular dystrophies (LGMDs) are a group of heterogeneous inherited diseases predominantly characterized by limb-girdle muscle weakness and dystrophic changes on histological analysis. The frequency of LGMD subtypes varies among regions in China and ethnic populations worldwide. Here, we analyzed the prevalence of LGMD subtypes, their corresponding clinical manifestations, and molecular data in a cohort of LGMD patients in Southeast China.MethodsA total of 81 consecutive patients with clinically suspected LGMDs from 62 unrelated families across Southeast China were recruited for targeted next-generation sequencing and whole-exome sequencing from July 2017 to February 2020.ResultsAmong 50 patients (41 families) with LGMDs, the most common subtypes were LGMD-R2/LGMD2B (36.6%) and LGMD-R1/LGMD2A (29.3%). Dystroglycanopathies (including LGMD-R9/LGMD2I, LGMD-R11/LGMD2K, LGMD-R14/LGMD2N and LGMD-R20/LGMD2U) were the most common childhood-onset subtypes and were found in 12.2% of the families. A total of 14.6% of the families had the LGMD-R7/LGMD2G subtype, and the mutation c.26_33dupAGGTGTCG in TCAP was the most frequent (83.3%). The only patient with the rare subtype LGMD-R18/LGMD2S had TRAPPC11 mutations; had a later onset than those previously reported, and presented with proximal‒distal muscle weakness, walking aid dependency, fatty liver disease and diabetes at 33 years of age. A total of 22.0% of the patients had cardiac abnormalities, and one patient with LMNA-related muscular dystrophy/LGMD1B experienced sudden cardiac death at 37 years of age. A total of 15.4% of the patients had restrictive respiratory insufficiency. Muscle imaging in patients with LGMD-R1/LGMD2A and LGMD-R2/LGMD2B showed subtle differences, including more severe fatty infiltration of the posterior thigh muscles in those with LGMD-R1/LGMD2A and edema in the lower leg muscles in those with LGMD-R2/LGMD2B.ConclusionWe determined the prevalence of different LGMD subtypes in Southeast China, described the detailed clinical manifestations and distinct muscle MRI patterns of these LGMD subtypes and reported the frequent mutations and the cardiorespiratory involvement frequency in our cohort, all of which might facilitate the differential diagnosis of LGMDs, allowing more timely treatment and guiding future clinical trials.