Pathological Stage Research Articles

The Effect of Gender on the Intestinal Flora of Colorectal Cancer Under Different Stages.

This study aims to determine whether gender is a factor in the interplay between the human intestinal flora and colorectal cancer (CRC), ultimately providing new evidence for the clinical prediction and management of CRC in different genders. In this study, we included 186 untreated CRC patients, and classified them into two groups based on pathological staging: Groups Ⅰ-Ⅱ and Groups Ⅲ-Ⅳ, with male and female groups within each group. We collected preoperative fecal samples from these patients and performed 16S rRNA gene sequencing to analyze their intestinal flora. In the CRC Stages I-II cohort, the gut microbiota of the female group exhibited greater diversity and abundance compared to the male group, with a total of 13 gut microbiota demonstrating significant disparities. Notably, s__Parabacteroides gordonii, s__Bacteroides faecis, and s__Bacteroides nordii were found to be more prevalent in the female group relative to the male group. Within the CRC Stages III-IV cohort, 51 gut microbiota exhibited significant differences between the genders. In the immunocyte composition of fecal samples from patients with CRC, a higher proportion of naive B cells is observed in the male group as compared to the female group. In female CRC patients within the CRC Stages III-IV cohort, Actinomyces exhibited a significant negative correlation with activated dendritic cells, CD4+ memory T cells, and eosinophils. In male CRC patients within the CRC Stages III-IV cohort, Actinomyces demonstrated a significant positive correlation with naive B cells and a significant positive correlation with immune activation genes TNFRSF25 and TMIGD2. In female CRC patients within the CRC Stages III-IV cohort, Actinomyces showed a significant negative correlation with activated dendritic cells, CD4+ memory T cells, and eosinophils, and a significant positive correlation with immune activation genes TNFSF13B, LTA, KLRK1, and CXCL12. In the CRC Stages I-II group, the female group's intestinal flora is more diverse and richer than the male group. In the CRC Stages III-IV group, there are a total of 51 different intestinal flora in both the male and female groups. We also found that Actinomyces affects the occurrence and development of CRC in the male and female groups through different pathways. The results show that the intestinal flora differs between male and female CRC patients and is closely associated with cancer development.

Microglial CD2AP deficiency exerts protection in an Alzheimer’s disease model of amyloidosis

BackgroundThe CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton and protein trafficking. Single nucleotide polymorphisms (SNPs) in the CD2AP gene have been associated with Alzheimer’s disease (AD). However, the functional role of CD2AP, especially its role in microglia during AD onset, remains elusive.MethodsCD2AP protein levels in cultured primary cells and in 5xFAD mice was studied. Microglial CD2AP-deficient mice were crossed with 5xFAD mice and the offspring were subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, and biochemistry analysis. Primary microglia were also isolated for assessing their uptake and morphology changes.ResultsWe find that CD2AP is abundantly expressed in microglia and its levels are elevated in the brain of AD patients and the 5xFAD model mice at pathological stages. We demonstrate that CD2AP haploinsufficiency in microglia significantly attenuates cognitive and synaptic deficits, weakens the response of microglia to Aβ and the formation of disease-associated microglia (DAM), and alleviates synapse loss in 5xFAD mice. We show that CD2AP-deficient microglia exhibit compromised uptake ability. In addition, we find that CD2AP expression is positively correlated with the expression of the complement C1q that is important for synapse phagocytosis and the formation of DAM in response to Aβ deposition. Moreover, we reveal that CD2AP interacts with colony stimulating factor 1 receptor (CSF1R) and regulates CSF1R cell surface levels, which may further affect C1q expression.ConclusionsOur results demonstrate that CD2AP regulates microgliosis and identify a protective function of microglial CD2AP deficiency against Aβ deposition, suggesting the importance of detailed investigation of AD-associated genes in different brain cells for thoroughly understanding their exact contribution to AD.

Randomized controlled phase III study comparing chemotherapy alone versus conversion surgery after a remarkable response to chemotherapy in patients with initially unresectable cStage IVB or pStage IV gastric cancer (JCOG2301, Conversion study).

The standard approach for stage IV gastric cancer is palliative chemotherapy. However, despite the advancements in various chemotherapy regimens, the prognosis remains poor, highlighting the urgent need to develop more effective treatment strategies. The controversy persists regarding the integration of a local therapy including surgery in the management of unresectable stage IV gastric cancer. This randomized phase III trial aims to confirm the additional benefit of conversion surgery following palliative chemotherapy compared with palliative chemotherapy alone with respect to overall survival in patients initially diagnosed with unresectable clinical stage IVB or pathological stage IV gastric cancer after a remarkable response to chemotherapy. This study plans to enroll 126 patients from 63 institutions in Japan for 5years, and it has been registered in the Japan Registry of Clinical Trials as jRCTs031240340 (https://jrct.niph.go.jp/latest-detail/jRCTs031240340).

Local excision for middle-low rectal cancer after neoadjuvant chemoradiation: A retrospective study from a single tertiary center

BACKGROUND Rectal cancer has become one of the leading malignancies threatening people’s health. For locally advanced rectal cancer (LARC), the comprehensive strategy combining neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant chemotherapy has emerged as a standard treatment regimen, leading to favorable local control and long-term survival. However, in recent years, an increasing attention has been paid on the exploration of organ preservation strategies, aiming to enhance quality of life while maintaining optimal oncological treatment outcomes. Local excision (LE), compared with low anterior resection (LAR) or abdominal-perineal resection (APR) was introduced dating back to 1970’s. LE has historically been linked to a heightened risk of recurrence compared to TME, potentially due to occult lymph node metastasis and intraluminal recurrence. Recent evidence has demonstrated that LE might be an alternative approach, instead of LAR or APR, in cases with favorable tumor regression after NCRT with potentially better quality of life. Therefore, a retrospective analysis of clinicopathological data from mid-low LARC patients who underwent LE after NCRT was conducted, aiming to evaluate the treatment's efficacy, safety, and oncologic prognosis. AIM To explore the safety, efficacy, and long-term prognosis of LE in patients with mid-low rectal cancer who had a good response to NCRT. METHODS Patients with LE between 2012 to 2021 were retrospectively collected from the rectal cancer database from Gastro-intestinal Ward III in Peking University Cancer Hospital. The clinicopathological features, postoperative complications, and long-term prognosis of these patients were analyzed. The Kaplan-Meier method was used to create cancer-specific survival curve, and the log-rank test was used to compare the differences regarding outcomes. RESULTS A total of 33 patients were included in this study. The median interval between NCRT and surgery was 25.4 (range: 8.7-164.4) weeks. The median operation time was 57 (20.0-137.0) minutes. The initial clinical T staging (cT): 9 (27.3%) patients were cT2, 19 (57.6%) patients were cT3, and 5 (15.2%) patients were cT4; The initial N staging (cN): 8 patients (24.2%) were cN negative, 25 patients (75.8%) were cN positive; The initial M stage (cM): 2 patients (6.1%) had distant metastasis (ycM1), 31 (93.9%) patients had no distant metastasis (cM0). The pathological results: 18 (54.5%) patients were pathological T0 stage (ypT0), 6 (18.2%) patients were ypT1, 7 (21.2%) patients were ypT2, and 2 (6.1%) patients were ypT3. For 9 cT2 patients, 5 (5/9, 55.6%) had a postoperative pathological result of ypT0. For 19 cT3 patients, 11 (57.9%) patients were ypT0, and 2 (40%) were ypT0 in 5 cT4 patients. The most common complication was chronic perineal pain (71.4%, 5/7), followed by bleeding (43%, 3/7), stenosis (14.3%, 1/7), and fecal incontinence (14.3%, 1/7). The median follow-up time was 42.0 (4.0-93.5) months. For 31 patients with cM0, the 5-year disease-free survival (DFS) rate, 5-year local recurrence-free survival (LRFS) rate, and 5-year overall survival (OS) rate were 88.4%, 96.7%, and 92.9%, respectively. There were significant differences between the ycT groups concerning either DFS (P = 0.042) or OS (P = 0.002) in the Kaplan-Meier analysis. The LRFS curve of ycT ≤ T1 patients was better than that of ycT ≥ T2 patients, and the P value was very close to 0.05 (P = 0.070). The DFS curve of patients with ypT ≤ T1 was better than that of patients with ypT ≥ T2, but the P value was not statistically significant (P = 0.560). There was a significant difference between the ypT groups concerning OS (P = 0.014) in the Kaplan-Meier analysis. The LRFS curve of ypT ≤ T1 patients was better than that of ypT ≥ T2 patients, and the P value was very close to 0.05 (P = 0.070). Two patients with initial cM1 were alive at the last follow-up. CONCLUSION LE for rectal cancer with significant tumor regression after NCRT can obtain better safety, efficiency, and oncological outcome. Minimally invasive or nonsurgical treatment with patient participation in decision-making can be performed for highly selected patients. Further investigation from multiple centers will bring better understanding of potential advantages regarding local resection.

Clinicopathological significance of sulfite oxidase expression in surgically resected lung adenocarcinoma.

The coenzyme sulfite oxidase (SUOX), located in mitochondria, plays a role in redox and metabolism. Its expression has been associated with cancer progression and prognosis. Lung cancer has a high incidence rate and poor prognosis. We aim to clarify its expression in lung adenocarcinomas and investigated the utility of SUOX expression as a recurrence factor in operable lung adenocarcinoma. We used 60 formalin-fixed paraffin-embedded samples of operable primary lung adenocarcinoma between 2017 and 2018 to immunohistochemically assess SUOX expression levels. Patients were classified into a high or low SUOX expression group, and the associations of SUOX expression with clinicopathological findings and recurrence were analyzed. We revealed that high SUOX expression was significantly (p < 0.05) associated with sex, low Brinkman index, histological type, histological grade and positive for epidermal growth factor receptor (EGFR) mutation. High SUOX expression (HR = 10.218, 95% CI 1.758‒59.376, p = 0.0096) and pathological Stage (HR = 7.538, 95% CI 1.95‒29.14, p = 0.0034) were independently associated with relapse free survival. High SUOX expression may be a new indicator of recurrence risk in surgically resected lung adenocarcinomas.

Effects of the COVID-19 pandemic on surgical treatment for thoracic malignant tumor cases in Japan: a national clinical database analysis.

Surgical care has been significantly affected by the COVID-19 pandemic. This study was conducted to evaluate the effects of the pandemic on lung cancer and mediastinal tumor surgery. Changes in the number of surgical procedures for lung cancer and mediastinal tumors were analyzed using the National Clinical Database of Japan. Patient characteristics, including disease stage and histological type, from 2019 to 2022 were evaluated using annual datasets. Comparisons with 2019 showed that the number of patients who underwent surgery for primary lung cancer or a mediastinal tumor decreased in 2020 and then remained stable. There were no clinically significant changes in the trend over the four-year period regarding the number of patients for each clinical and pathological stage of lung cancer. Regarding mediastinal tumors, there was no significant difference in tumor size between years. There was a slight change in the selection of surgical indication during the second quarter of 2020, although its impact on annual trends in the stage distribution for lung cancer and primary disease for mediastinal tumors was minimal. Analyses of lung cancer and mediastinal tumor surgery cases in Japan during the COVID-19 pandemic showed no significant disease profile changes related to treatment delay.

Longitudinal Imaging Biomarkers Correlate with Progressive Motor Deficit in the Mouse Model of Charlevoix-Saguenay Ataxia.

In autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease, severity and age of onset vary greatly, hindering to objectively measure and predict clinical progression. Thickening of the retinal nerve fiber layer is distinctive of ARSACS patients, as assessed by optical coherence tomography, whereas conventional brain magnetic resonance imaging findings include both supratentorial and infratentorial changes. Because longitudinal imaging studies in ARSACS patients are not available to define these changes as biomarkers of disease progression, we aimed to address this issue in the ARSACS mouse model. We performed longitudinal retinal OCT and brain MRI in the Sacs-/- ARSACS mouse model, alongside motor and coordination assessment in the beam walking test. We also investigated visual function and the molecular mechanisms underlying RNFL increased thickness by histology and immunofluorescence. We demonstrated that RNFL thickening by OCT gradually increases in the early stages of pathology in the Sacs-/- mouse model, reflecting the progression of motor impairment, and later reaches a plateau when thinning of the posterior corpus callosum becomes detectable by MRI. Mechanistically, we unveiled that RNFL thickening is associated with aberrant accumulation of non-phosphorylated neurofilament H and glial fibrillary acidic protein. We also uncovered mild signs of myelin pathology coherent with increased latency of visual evoked potentials, and altered retinal activation by photopic electroretinography. We show that both RNFL thickening and MRI changes may represent biomarkers of disease progression in the Sacs-/- mouse model. Our data gathers knowledge instrumental to clinical studies, holding potential as readout for treatment efficacy. ANN NEUROL 2024.

BUD23 promote the cell proliferation ability by affecting the PPAR signaling pathways: evidence from the online dataset and cell experiment

IntroductionProstate cancer is a major public health challenge for men worldwide, being the second most common cancer diagnosis and the fifth leading cause of cancer-related deaths among men. The etiology of prostate cancer is multifactorial, with age, genetic predispositions, and lifestyle factors playing critical roles. The role of the peroxisome proliferator-activated receptors (PPARs) in prostate cancer remains complex and not fully elucidated.MethodsTranscriptomic data from The Cancer Genome Atlas (TCGA) were utilized for this study. The data were analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA), Gene Ontology (GO) enrichment analysis, KEGG pathway analysis, and Gene Set Enrichment Analysis (GSEA). A prognosis-prediction model was constructed using Cox regression and LASSO analysis. Functional experiments, including Western blotting, quantitative PCR (qPCR), Cell Counting Kit-8 (CCK-8) assays, and EdU incorporation assays, were performed to validate the role of BUD23 in prostate cancer.ResultsSignificant differences were observed in the immune microenvironment and HLA gene expression profiles between high and low PPAR expression groups in prostate cancer. The high PPAR group exhibited a less active immune microenvironment with higher fractions of immunosuppressive T regulatory cells (Tregs). A robust prognostic model identified key genes, including BUD23, associated with patient survival. Elevated BUD23 expression was correlated with more aggressive clinical features such as advanced pathological stages, nodal metastasis, and higher Gleason scores. Knockdown of BUD23 in PC-3 and LNCaP prostate cancer cell lines significantly inhibited cell proliferation. Western blotting and qPCR confirmed effective BUD23 knockdown, and CCK-8 and EdU assays demonstrated reduced cell proliferation. BUD23 knockdown resulted in significant reductions in PPAR-α, PPAR-β, and PPAR-γ protein levels, suggesting a regulatory axis between BUD23 and PPARs in prostate cancer.ConclusionThe study highlights the distinct roles of PPARα, PPARβ/δ, and PPARγ in prostate cancer progression and their potential as therapeutic targets. Elevated BUD23 expression is associated with aggressive prostate cancer features and patient survival, making it a potential prognostic biomarker. The knockdown of BUD23 not only inhibited cell proliferation but also reduced the expression of PPAR-related proteins, indicating a potential regulatory axis between BUD23 and PPARs. These findings suggest that targeting BUD23 could modulate PPAR signaling and inhibit tumor growth in prostate cancer.

NMR-based metabolomics combined with metabolic pathway analysis reveals metabolic heterogeneity of colorectal cancer tissue at different anatomical locations and stages.

Colorectal cancer (CRC) still remains the leading cause of cancer death worldwide. This study aimed to profile the metabolic differences of colorectal cancer tissues (CCT) at different stages and sites, as compared with their distant noncancerous tissues (DNT), to investigate the temporal and spatial heterogeneities of metabolic characterization. Our NMR-based metabolomics fingerprinting revealed that many of the metabolite levels were significantly altered in CCT compared to DNT and esophageal cancer tissues, indicating deregulations of glucose metabolism, one-carbon metabolism, glutamine metabolism, amino acid metabolism, fatty acid metabolism, TCA cycle, choline metabolism, and so forth. A total of five biomarker metabolites, including glucose, glutamate, alanine, valine and histidine, were identified to distinguish between early and advanced stages of CCT. Metabolites that distinguish the different anatomical sites of CCT include glucose, glycerol, glutamine, inositol, succinate, and citrate. Those significant metabolic differences in CRC tissues at different pathological stages and sites suggested temporal and spatial heterogeneities of metabolic characterization in CCT, providing a metabolic foundation for further study on biofluid metabolism in CRC early detection.

Plasma p-tau immunoassays in clinical research for Alzheimer's disease.

The revised biomarker framework for diagnosis and staging of Alzheimer's disease (AD) relies on amyloid beta (Aβ) and tau pathologies as core markers, and markers for adjacent pathophysiology, such as neurodegeneration and inflammation. Many of the core fluid biomarkers are phosphorylated tau (p-tau) fragments, with p-tau217 showing a prominent association with Aβ and tau. While positron emission tomography (PET) imaging is well established, plasma p-tau assays are newer and likely to reduce the use of expensive, and less accessible cerebrospinal fluid and PET imaging tests, thereby promoting wider access to AD screening. There is a need for greater understanding of how the various plasma p-tau species reflect different pathological processes of AD and how different immunoassays perform. This review surveys the available immunoassays and highlights their strengths and limitations in different contexts of use. Assays need to be standardized to maximize their impact on AD clinical research, and patient diagnosis and management. HIGHLIGHTS: Different plasma phosphorylated tau (p-tau) species reflect different pathological processes of Alzheimer's disease (AD), with p-tau231 showing the greatest association with the earliest increases in brain amyloid beta (Aβ) accumulation, while p-tau217 shows greater association with both brain Aβ and early tau pathology, and other p-tau and tau fragment species show greater association with later stages of brain tau pathology. Plasma p-tau217 has proven to be an excellent biomarker for AD pathology due to its close association with both brain Aβ and tau pathology, as well as its large dynamic range. Many different assays with varying performance exist for the same p-tau species, with mass spectrometry assays performing uniformly well, and several immunoassays achieving comparable performance. "Round robin" head-to-head studies have been performed to compare different assays for several key plasma biomarkers, including p-tau181 and p-tau217, but additional head-to-head studies are needed, especially for new analytes and for measuring performance in diverse populations. Plasma immunoassays have the potential to increase accessibility of early diagnostic testing for a broad population, including diverse historically under-represented and under-served populations, due to the potential to be implemented globally, including in primary care settings; however, further research is needed to validate the optimal cutoffs for each assay for real-world clinical usage. Eventually, clinical implementation of a two-step workflow may allow standalone use of plasma testing in certain contexts, minimizing the need for confirmation with costly and less accessible cerebrospinal fluid/positron emission tomography testing.

Significance of the modified global leadership initiative on malnutrition (GLIM) criteria malcondition for patients with biliary tract cancer.

This study investigated the significance of the Global Leadership Initiative on Malnutrition (GLIM) for patients with resected biliary tract cancers. The subjects of this retrospective analysis were 114 patients who underwent radical surgery for cholangiocarcinoma between 2018 and 2023. We analyzed both handgrip force and skeletal muscle area and classified patients as having GLIM malnutrition or modified GLIM malcondition. We also evaluated clinicopathological factors, short-term outcomes, and prognoses. The GLIM criteria identified 47 patients (41.2%) with malnutrition and 13 patients (11.4%) with modified GLIM malcondition. Overall survival (P = 0.009) and recurrence-free survival (P = 0.016) were significantly different between the well-nourished and malnourished patients according to the GLIM criteria. Furthermore, modified GLIM criteria malcondition was a significant prognostic factor for both recurrence-free and overall survival (P = 0.002 and P < 0.001, respectively). Multivariate analysis identified a higher carcinoembryonic antigen level and modified GLIM malcondition as predictors of overall and recurrence-free survival. Pathological stage ≥ III was also a predictor of recurrence-free survival. On comparing the prognoses of modified GLIM malcondition and GLIM malnutrition using the Akaike Information Criteria, the modified GLIM malcondition was identified as a stronger prognostic factor. A modified GLIM malcondition can be a highly useful prognostic marker for patients with resected biliary tract cancer.

Inferring disease progressive stages in single-cell transcriptomics using a weakly-supervised deep learning approach

Application of single-cell/nucleus genomic sequencing to patient-derived tissues offers potential solutions to delineate disease mechanisms in human. However, individual cells in patient-derived tissues are in different pathological stages, and hence such cellular variability impedes subsequent differential gene expression analyses. To overcome such heterogeneity issue, we present a novel deep learning approach, scIDST, that infers disease progressive levels of individual cells with weak supervision framework. The inferred disease progressive cells displayed significant differential expression of disease-relevant genes, which could not be detected by comparative analysis between patients and healthy donors. In addition, we demonstrated that pretrained models by scIDST are applicable to multiple independent data resources, and advantageous to infer cells related to certain disease risks and comorbidities. Taken together, scIDST offers a new strategy of single-cell sequencing analysis to identify bona fide disease-associated molecular features.

Letter to the Editor: Insight into functional tricuspid valve regurgitation pathogenesis, pathological stages, and surgical management

Letter to the Editor: Insight into functional tricuspid valve regurgitation pathogenesis, pathological stages, and surgical management

Early diagnostic value of ECT whole-body bone imaging combined with PINP and β-CTX for bone metastasis of lung cancer.

This research was aimed at investigating the early diagnostic value of emission computed tomograph (ECT) whole-body bone imaging combined with PINP and β-CTX for bone metastasis of lung cancer. Case data of 86 lung cancer patients were categorized into lung cancer with bone metastasis (LCWBM, 46 cases) and lung cancer without bone metastasis (LCWOBM, 40 cases) groups according to the presence or absence of bone metastasis. Patients' general information were collected. ECT whole-body bone imaging was used to detect bone metastases and the grading of the extent of disease (EOD) in both groups, and electrochemiluminescence was utilized to detect the serum levels of PINP and β-CTX. Spearman correlation analysis was employed to evaluate the correlation between EOD grading and PINP and β-CTX levels. Logistic univariate and multivariate regression was implemented to analyze the risk factors of bone metastasis of lung cancer. Receiver operating characteristic (ROC) curve was applied to analyze the diagnostic efficacy of the single test of ECT whole-body bone imaging, PINP, or β-CTX and the combination of the three tests. The differences in pathological type, clinical stage and EOD grading, the number of positive ECT cases, and the expression levels of PINP and β-CTX between the LCWBM and LCWOBM groups were statistically significant. In LCWBM patients with different EOD grading, the trends of the expression of PINP and β-CTX were grade 3 > grade 2 > grade 1 and grade 0. Further correlation analyses revealed that EOD grading showed a significant positive correlation with the PINP and β-CTX expression levels. Univariate logistic regression analysis demonstrated that adenocarcinoma, TNM stage IV, ECT positivity, and high expression of PINP and β-CTX were associated with bone metastasis of lung cancer, and multivariate logistic regression analysis indicated that ECT positivity, high expression of PINP and β-CTX were independent risk factors for bone metastasis of lung cancer. The area under the curve (AUC) of ECT, PINP, and β-CTX alone for the diagnosis of bone metastasis of lung cancer were 0.872, 0.888, and 0.874, respectively, and the AUC for the combined diagnosis of the three was 0.963, which was greater than that of any one of the individual indices, with a sensitivity of 86.96% and a specificity of 97.50% at a Youden index of 0.845. ECT whole-body bone imaging combined with PINP and β-CTX has high diagnostic value for bone metastasis of lung cancer.

Prognostic Implications of the Number of Lymph Node Metastases in Oral Tongue Squamous Cell Carcinoma: A Population Study of the SEER Database and an Institutional Registry.

To investigate the impact of the number of positive lymph nodes (PLNs) on long-term survival and pathological nodal stage in patients with oral tongue squamous cell carcinoma (OTSCC). Newly diagnosed and nonmetastatic adult patients with OTSCC who underwent curative resection were identified between January 2010 and December 2020. External validation was performed via the SEER registry. Multivariate Cox proportional hazards model was employed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of pathological nodal features. Propensity score matching (PSM) was used to assess effect of adjuvant chemoradiotherapy (ACRT). Among 518 curative-intent OTSCC patients, the number of PLNs independently predicted overall survival (OS), surpassing other pathological nodal features, including extranodal extension, laterality, and lower neck involvement. Patients with 1 or 2 PLNs had comparable worse OS than those with no PLN (median OS of 1 PLN vs. 2 PLNs vs. 0 PLN: 35.1 vs. 30.5 vs. 40.2 months), but better than those with ≥ 3 PLNs (median OS of 1-2 PLNs vs. 3 PLNs: 32.1 vs. 19.0 months). A proposed nodal category with 0, 1-2 PLNs, and ≥ 3 PLNs exhibited increasingly worse OS (HR of 1-2 PLNs and ≥ 3 PLNs vs. 0 PLN: 2.98 [95% CI: 1.89-4.71], p < 0.001; 5.47 [95% CI: 3.33-9], p < 0.001; respectively) and showed improved prediction power versus current pN staging (C-index: 0.717 vs. 0.713, p < 0.001). PSM analysis revealed that ACRT benefited patients with advanced nodal disease (≥ 3 PLNs) and improved OS. These findings were validated in SEER registry. The number of PLNs is a better predictor of overall tumor burden for OTSCC and could be a more accurate metric for survival estimation, which should be considered in future simplified pathological nodal staging for better risk stratification and decision-making in subsites of the oral cavity.

Organ-confined pT2 ISUP4/5 vs. nonorgan confined pT3/4 ISUP2 vs. ISUP3 prostate cancer: Differences in biochemical recurrence-free survival after radical prostatectomy

BackgroundTo test for differences in organ-confined pathological tumor stage (pT) and intermediate International Society of Urological Pathologists (ISUP) grade vs. nonorgan confined pT stage and high ISUP grade and biochemical recurrence (BCR) after radical prostatectomy (RP). MethodsRelying on a tertiary-care database, prostate cancer patients undergoing RP between January 2014 and December 2021 were stratified according to their combination of pT stage and ISUP grade in RP specimens (pT2 ISUP4/5 vs. pT3/4 ISUP2 vs. pT3/4 ISUP3). As Active Surveillance is recommended in ISUP1, these patients were excluded. Moreover, patients with pT2 ISUP2/3 are known for their good prognosis and pT3/4 ISUP4/5 patients for their poor prognosis. Therefore, these patients were also excluded from analyses. Kaplan–Meier survival analyses and multivariable Cox regression models addressed BCR after RP. ResultsOf 215 RP patients, 29 (13%) exhibited pT2 ISUP4/5 vs. 122 (57%) pT3/4 ISUP2 vs. 64 (30%) pT3/4 ISUP3 pathology. In survival analyses, 3-year BCR-free survival rates were 95% in pT2 ISUP4/5 vs. 88% in pT3/4 ISUP2 vs. 65% in pT3/4 ISUP3 patients (P < 0.001). In multivariable Cox regression models addressing BCR, pT3/4 ISUP3 pathology was associated with higher BCR rate relative to pT2 ISUP4/5 pathology (hazard ratio 3.42, 95% confidence interval 1.07-10.94; P = 0.039), but not pT3/4 ISUP2 pathology (P = 0.6). ConclusionCompared to prostate cancer patients with pT2 ISUP4/5 pathology, the combination of pT3/4 ISUP3 pathology is associated with higher risk of BCR after RP. In consequence, patients with pT3/4 ISUP3 pathology should be considered for a closer postoperative follow-up.

Proposed Ninth Edition TNM Staging System for Lung Cancer: Guide for Radiologists.

Lung cancer continues to be the primary cause of cancer-related deaths globally. Precise staging is imperative for the development of successful treatment approaches and improvement of patient outcomes. Traditionally, lung cancer staging has depended on the TNM staging system, and the International Association for the Study of Lung Cancer (IASLC) has recently recommended modifications. The updated classification for the ninth edition of the TNM staging system (TNM-9), slated to take effect in January 2025, is derived from a thorough analysis of a newly established large international database of lung cancer cases compiled by the IASLC. Proposed changes in TNM-9 include the following: (a) The mediastinal nodal category (N2) was split into single-station (N2a) and multiple-station (N2b) subcategories, and (b) multiple extrathoracic metastatic lesions (M1c) were split into single organ system (M1c1) and multiple organ systems (M1c2) subcategories. Considering these revisions, adjustments have been made to the established stage groups. In terms of pathologic nodal staging, patients in the post-neoadjuvant ypN category demonstrated worse prognosis than those in the similar non-neoadjuvant pN category. Understanding the fundamental changes introduced in TNM-9 enables radiologists to precisely determine the clinical stage of lung cancer and enhance therapeutic approaches.

Prognostic Value and Therapeutic Significance of CCL Chemokines in Gastric Cancer.

Gastric cancer is one of the most common malignant tumours of the gastrointestinal tract, which has a significant negative impact on human health. CCL chemokines play important roles in a variety of tumor microenvironments; nevertheless, gastric cancer has surprisingly limited associations with CCL chemokines. In our study, we comprehensively utilized bioinformatics analysis tools and databases such as cBioPortal, UALCAN, GEPIA, GeneMANIA, STRING, and TRRUST to clarify the clinical significance and biology function of CCL chemokines in gastric cancer. The mRNA expression levels of CCL1/3/4/5/7/8/14/15/18/20/21/22/26 were up-regulated, while the mRNA expression levels of CCL2/11/13/16/17/19/23/24/25/28 were down-regulated. The chemokine significantly associated with the pathological stage of gastric cancer is CCL2/11/19/21. In gastric cancer, the expression level of CCL chemokines was not associated with disease-free survival, but low expression of CCL14 was significantly associated with longer overall survival. Therein, associated with the regulation of CCL chemokines are only 10 transcription factors (RELA, NFKB1, STAT6, IRF3, REL, SPI1, STAT1, STAT3, JUN and SP1). The major biological process and functional enrichment of CCL chemokines are to induce cell-directed migration. These results may indicate that CCL chemokines may be immunotherapeutic targets and promising prognostic biomarkers for gastric cancer.

Bladder sparing management for muscle-invasive bladder cancer after a complete clinical response: ready for prime time?-a narrative review.

A standard of care for muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Given recent improvements in NAC and the morbidity associated with RC, bladder-sparing therapy has been investigated as a promising treatment for patients with MIBC who experience a complete clinical response (CCR) to systemic therapy. However, clinical staging is unreliable, making it challenging to determine ideal candidates for bladder-sparing therapy. Our primary objective is to review the efficacy of NAC, strategies for determining a CCR as a surrogate for a complete pathologic response, and the emerging role of imaging, tumor genomics, and biomarkers in selecting candidates for bladder-sparing therapy. We surveyed the literature for studies investigating the outcomes of current treatment modalities for MIBC and methods for determining a CCR following systemic therapy as well as the impact this has on pathologic staging. Studies employing imaging, tumor biomarkers, and genomics were included. Clinical staging with cystoscopy or transurethral resection shows significant discordance with final pathology, with high rates of understaging. Multiparametric magnetic resonance imaging (mpMRI) has shown strong utility in determining the presence of MIBC, but it has yet to reliably identify CCR. Meanwhile, somatic DNA damage repair mutations and biomarkers such as circulating and urinary tumor DNA are strong predictors of recurrence, showing promise in predicting and monitoring a CCR to systemic therapy. Multiple ongoing trials are currently assessing the use of biomarkers and genomic analyses in determining eligibility for bladder-sparing therapy. While no one method has reliably demonstrated the ability to detect a true CCR, a multimodal approach involving imaging, biomarkers, and genomic analyses holds promise. We eagerly await the results of clinical trials investigating these tools, which may allow for the safe recommendation of bladder-sparing therapy.

Pan-cancer analysis combined with experimental validation revealed that KTN1 is an immunological and prognostic biomarker.

Kinectin 1 (KTN1) is a membrane protein involved in intracellular organelle motility. However, the role of KTN1 in human pan-cancer lacks systematic analysis and evaluation. The aim of this study is to evaluate the expression profile and clinical value in human cancers by performing a pan-cancer analysis of KTN1. The expression of KTN1 and its correlation with cancer-associated fibroblasts (CAFs) infiltration were analyzed in TIMER2.0. The survival analysis, pathological stage correlation, and co-expression gene correlation analysis of KTN1 were performed on GEPIA2.0. We investigated the protein expression level of KTN1 in tumors through UALCAN. The cBioportal platform was used to analyze the variation frequency and type of KTN1. We used STRING database for protein-protein interaction (PPI) network analysis. Cell Counting Kit-8 (CCK8) and colony formation and transwell assay were performed to investigate the proliferation and migration abilities of head and neck squamous cell carcinoma (HNSC) cells with KTN1 knockdown. KTN1 was differentially expressed in 12 kinds of cancer tissues compared with correspondent normal tissues. Meanwhile, the high expression of KTN1 was negatively correlated with the prognosis of HNSC, adrenocortical carcinoma (ACC), and liver hepatocellular carcinoma (LIHC). Further analysis suggested that patients with KTN1 mutations had better overall survival (OS) and progression-free survival than those without mutations among several cancers. Moreover, the level of CAFs and KTN1 expression were significantly correlated in 12 types of cancer. Mechanically, co-expression analysis showed the positive association between KTN1 and KTN1 antisense RNA 1 (KTN1-AS1), MNAT1 component of CDK activating kinase (MNAT1), N-alpha-acetyltransferase 30 (NAA30), protein phosphatase 2 regulatory subunit B'epsilon (PPP2R5E), and proteasome 26S subunit (PSMC6), which are mainly involved in the protein kinase AMP-activated catalytic subunit alpha 1 (AMPK) signaling pathway that regulates the progression of tumors. The functional experiment revealed that KTN1 promotes the proliferation and metastasis of HNSC cells. The pan-cancer analysis of KTN1 revealed its significance in different cancers, which provides a new marker for the diagnosis and prognosis of cancers.