Unsupervised domain adaptation for histopathology image segmentation with incomplete labels.

Stain variations pose a major challenge to deep learning segmentation algorithms in histopathology images. Current unsupervised domain adaptation methods show promise in improving model generalization across diverse staining appearances but demand abundant accurately labeled source domain data. This paper assumes a novel scenario, namely, unsupervised domain adaptation based segmentation task with incompletely labeled source data. This paper propose a Stain-Adaptive Segmentation Network with Incomplete Labels (SASN-IL). Specifically, the algorithm consists of two stages. The first stage is an incomplete label correction stage, involving reliable model selection and label correction to rectify false-negative regions in incomplete labels. The second stage is the unsupervised domain adaptation stage, achieving segmentation on the target domain. In this stage, we introduce an adaptive stain transformation module, which adjusts the degree of transformation based on segmentation performance. We evaluate our method on a gastric cancer dataset, demonstrating significant improvements, with a 10.01% increase in Dice coefficient compared to the baseline and competitive performance relative to existing methods.

Blocking EGR1/TGF-ß1 and CD44s/STAT3 Crosstalk Inhibits Peritoneal Metastasis of Gastric Cancer.

Peritoneal metastasis (PM) continues to limit the clinical efficacy of gastric cancer (GC). Early growth response 1 (EGR1) plays an important role in tumor cell proliferation, angiogenesis and invasion. However, the role of EGR1 derived from the tumor microenvironment in reshaping the phenotypes of GC cells and its specific molecular mechanisms in increasing the potential for PM are still unclear. In this study, we reported that EGR1 was significantly up-regulated in mesothelial cells from GC peritoneal metastases, leading to enhanced epithelial-mesenchymal transformation (EMT) and stemness phenotypes of GC cells under co-culture conditions. These phenotypes were achieved through the transcription and secretion of TGF-ß1 by EGR1 in mesothelial cells, which could regulate the expression and internalization of CD44s. After being internalized into the cytoplasm, CD44s interacted with STAT3 to promote STAT3 phosphorylation and activation, and induced EMT and stemness gene transcription, thus positively regulating the metastasis of GC cells. Moreover, TGF-ß1 secretion in the PM microenvironment was significantly increased compared with the matched primary tumor. The blocking effect of SHR-1701 on TGF-ß1 was verified by inhibiting peritoneal metastases in xenografts. Collectively, the interplay of EGR1/TGF-ß1/CD44s/STAT3 signaling between mesothelial cells and GC cells induces EMT and stemness phenotypes, offering potential as a therapeutic target for PM of GC.

CrossU-Net: Dual-modality cross-attention U-Net for segmentation of precancerous lesions in gastric cancer.

Gastric precancerous lesions (GPL) significantly elevate the risk of gastric cancer, and precise diagnosis and timely intervention are critical for patient survival. Due to the elusive pathological features of precancerous lesions, the early detection rate is less than 10%, which hinders lesion localization and diagnosis. In this paper, we provide a GPL pathological dataset and propose a novel method for improving the segmentation accuracy on a limited-scale dataset, namely RGB and Hyperspectral dual-modal pathological image Cross-attention U-Net (CrossU-Net). Specifically, we present a self-supervised pre-training model for hyperspectral images to serve downstream segmentation tasks. Secondly, we design a dual-stream U-Net-based network to extract features from different modal images. To promote information exchange between spatial information in RGB images and spectral information in hyperspectral images, we customize the cross-attention mechanism between the two networks. Furthermore, we use an intermediate agent in this mechanism to improve computational efficiency. Finally, we add a distillation loss to align predicted results for both branches, improving network generalization. Experimental results show that our CrossU-Net achieves accuracy and Dice of 96.53% and 91.62%, respectively, for GPL lesion segmentation, providing a promising spectral research approach for the localization and subsequent quantitative analysis of pathological features in early diagnosis.

Paracrine activin B-NF-κB signaling shapes an inflammatory tumor microenvironment in gastric cancer via fibroblast reprogramming.

BACKGROUND: Important roles of INHBB in various malignancies are increasingly identified. The underlying mechanisms in gastric cancer (GC) microenvironment are still greatly unexplored. METHODS: The clinical significance of INHBB and the correlation between INHBB and p-p65 in GC were assessed through analyzing publicly available databases and human paraffin embedded GC tissues. The biological crosstalk of INHBB between GC cells and fibroblasts was explored both in vitro and in vivo. RNA-seq analyses were performed to determine the mechanisms which regulating fibroblasts reprogramming. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify the binding relationship of p65 and INHBB in GC cells. RESULTS: Our study showed that INHBB level was significantly higher in GC, and that increased INHBB was associated with poor survival. INHBB positively regulates the proliferation, migration, and invasion of GC cells in vitro. Also, activin B promotes the occurrence of GC by reprogramming fibroblasts into cancer-associated fibroblasts (CAFs). The high expression of INHBB in GC cells activates the NF-κB pathway of normal gastric fibroblasts by secreting activin B, and promotes fibroblasts proliferation, migration, and invasion. In addition, activin B activates NF-κB pathway by controlling TRAF6 autoubiquitination to induce TAK1 phosphorylation in fibroblasts. Fibroblasts activated by activin B can induce the activation of p65 phosphorylation of GC cells by releasing pro-inflammatory factors IL-1ß. p65 can directly bind to the INHBB promoter and increase the INHBB transcription of GC cells, thus establishing a positive regulatory feedback loop to promote the progression of GC. CONCLUSIONS: GC cells p65/INHBB/activin B and fibroblasts p65/IL-1ß signal loop led to the formation of a whole tumor-promoting inflammatory microenvironment, which might be a promising therapeutic target for GC.

Effects of Social Support, Family Resilience, and Individual Resilience on Fear of Cancer Recurrence Among Persons With Breast Cancer: A Cross-Sectional Study.

BACKGROUND: There is limited research exploring the psychological and social predictors of fear of cancer recurrence (FCR). OBJECTIVE: This study tested the effects of social support, family resilience, and individual resilience on FCR among persons with breast cancer. METHODS: A convenience sampling method was used to select 214 participants from March to August 2021 in 1 tertiary hospital in Jinan, China. Data were collected using self-administered questionnaires. Path analysis was adopted to explore the effects of social support, family resilience, and individual resilience on FCR. RESULTS: Findings showed that 94.6% of the participants reached a clinical level of FCR. Social support (ß = -.75, p < .01) and individual resilience (ß = -.32, p < .01) negatively and directly impacted FCR. Family resilience indirectly impacted FCR through individual resilience (ß = -.22, 95% confidence interval (CI): -.34 to -.08). Social support indirectly impacted FCR through family resilience and individual resilience (ß = -.15, 95% CI: -.23 to -.06). CONCLUSIONS: Persons with breast cancer experienced a high level of FCR. Individual resilience was a mediator between family resilience and FCR. Resilience (individual resilience and family resilience) partially mediated the effects of social support on FCR. The findings indicate that measures focused on improving individual resilience, family resilience, and social support should be considered by nurses, which are helpful for easing FCR.

A deep learning model using hyperspectral image for EUS-FNA cytology diagnosis in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIMS: Endoscopic ultrasonography-guided fine-needle aspiration/biopsy (EUS-FNA/B) is considered to be a first-line procedure for the pathological diagnosis of pancreatic cancer owing to its high accuracy and low complication rate. The number of new cases of pancreatic ductal adenocarcinoma (PDAC) is increasing, and its accurate pathological diagnosis poses a challenge for cytopathologists. Our aim was to develop a hyperspectral imaging (HSI)-based convolution neural network (CNN) algorithm to aid in the diagnosis of pancreatic EUS-FNA cytology specimens. METHODS: HSI images were captured of pancreatic EUS-FNA cytological specimens from benign pancreatic tissues (n = 33) and PDAC (n = 39) prepared using a liquid-based cytology method. A CNN was established to test the diagnostic performance, and Attribution Guided Factorization Visualization (AGF-Visualization) was used to visualize the regions of important classification features identified by the model. RESULTS: A total of 1913 HSI images were obtained. Our ResNet18-SimSiam model achieved an accuracy of 0.9204, sensitivity of 0.9310 and specificity of 0.9123 (area under the curve of 0.9625) when trained on HSI images for the differentiation of PDAC cytological specimens from benign pancreatic cells. AGF-Visualization confirmed that the diagnoses were based on the features of tumor cell nuclei. CONCLUSIONS: An HSI-based model was developed to diagnose cytological PDAC specimens obtained using EUS-guided sampling. Under the supervision of experienced cytopathologists, we performed multi-staged consecutive in-depth learning of the model. Its superior diagnostic performance could be of value for cytologists when diagnosing PDAC.

Primary papillary epithelial tumor of the sella and posterior pituitary tumor show similar (epi)genetic features and constitute a single neuro-oncological entity.

BACKGROUND: "Primary papillary epithelial tumor of the sella (PPETS)" is a recently described rare tumor entity of the central nervous system (CNS) with stereotypic location in the sella. Comprehensive molecular investigations and epigenetic profiles of PPETS have not been performed to date. METHODS: We report a comprehensive clinical, histopathologic, and molecular assessment of 5 PPETS cases in comparison with a cohort composed of 7 choroid plexus papilloma (CPP), 7 central neurocytoma (CN), 15 posterior pituitary tumor (PPT) including 4 pituicytoma, 6 granular cell tumors of the sellar region (GCT), and 5 spindle cell oncocytoma. RESULTS: All PPETS had good outcomes. Immunohistochemically, PPETS tumors showed positive staining with TTF1, EMA, AE1/AE3, MAP2, and Vimentin, but were negatively stained with Syn, GFAP, CgA, and S100, and sporadically stained with Ki-67. In unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analyses of DNA-methylation data, PPETS and PPT tumors formed a distinct cluster irrespective of their histologic types. However, PPETS tumors did not cluster together with CPP and CN samples. Similar findings were obtained when our samples were projected into the reference cohort of the brain tumor classifier. Substantial fractions of the PPETS and PPT tumors shared broadly similar chromosomal copy number alterations. No mutations were detected using targeted next-generation sequencing. CONCLUSIONS: Though more cases are needed to further elucidate the molecular pathogenesis of these tumors, our findings indicate that PPETS and PPT tumors may constitute a single neurooncological entity.

Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis.

Although advances in spatial transcriptomics (ST) enlarge to unveil spatial landscape of tissues, it remains challenging to delineate pathology-relevant and cellular localizations, and interactions exclusive to a spatial niche (e.g., tumor boundary). Here, we develop Cottrazm, integrating ST with hematoxylin and eosin histological image, and single-cell transcriptomics to delineate the tumor boundary connecting malignant and non-malignant cell spots in tumor tissues, deconvolute cell-type composition at spatial location, and reconstruct cell type-specific gene expression profiles at sub-spot level. We validate the performance of Cottrazm along the malignant-boundary-nonmalignant spatial axis. We identify specific macrophage and fibroblast subtypes localized around tumor boundary that interacted with tumor cells to generate a structural boundary, which limits T cell infiltration and promotes immune exclusion in tumor microenvironment. In this work, Cottrazm provides an integrated tool framework to dissect the tumor spatial microenvironment and facilitates the discovery of functional biological insights, thereby identifying therapeutic targets in oncologic ST datasets.

Clinical and Sonographic Features of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: A Retrospective Study.

ABSTRACT: This study was designed to investigate the clinical and sonographic features of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) as compared with classical papillary thyroid carcinoma (cPTC), follicular adenoma (FA), and follicular thyroid carcinoma (FTC). A total of 178 patients were enrolled in this study. The clinical characteristics and sonographic features of thyroid nodules were compared between NIFTP and cPTC or FA/FTC. All nodules were reclassified according to the Thyroid Ultrasound Imaging Reporting and Data System and American Thyroid Association guidelines classification. The mean size of NIFTP was 29.91 ± 14.71 mm, which was larger than that of cPTC ( P = 0.000). Significant difference was found in lymph node metastases between NIFTP and cPTC ( P = 0.000). Most NIFTPs showed solid composition, hypoechoic echogenicity, smooth margin, wider than tall shape, none echogenic foci, absence of halo, and perinodular vascularity, which were similar with FA and FTC. Compared with NIFTP, hypoechoic and very hypoechoic, taller than wide, irregular margin, punctate echogenic foci, absence of halo, and low vascularity were more commonly observed in cPTC. There were statistical differences both in American College of Radiology Thyroid Ultrasound Imaging Reporting and Data System and in American Thyroid Association classification between NIFTP and cPTC ( P < 0.05), but there were no significant differences between NIFTP and FTC/FA ( P > 0.05). The ultrasonographic characteristics of NIFTP were obviously different from cPTC but overlapped with FTC and FA. Ultrasound could help increase preoperative attention of NIFTP in an appropriate clinical setting, which may lead to a more conservative treatment approach.

Prognostic role of iodine values for gastric cancer after neoadjuvant chemotherapy: a strong independent prognostic factor.

PURPOSE We aimed to systematically explore the value of iodine values calculated from dual-energy computed tomography (DECT) as potential prognostic factors for locally advanced gastric cancer (LAGC) patients undergoing neoadjuvant chemotherapy (NAC). METHODS Eighty-five LAGC patients were examined using DECT before and after NAC and were divided into responders and non-responders based on the tumor regression grade (TRG). The iodine values, including portal- and delayed-phase iodine uptake (IU-p and IU-d, mg/ml) and total iodine uptake (TIU-p and TIU-d, mg) were acquired. Correlations between the reduction ratios of iodine values and TRG were analyzed. The diagnostic performance of parameters for differentiating responders from non-responders was calculated. Kaplan-Meier method was used for survival analysis. RESULTS The reduction ratios of total iodine uptake (%△TIU-p and %△TIU-d) were significantly correlated with TRG (p < 0.001). The ypN stage, %△TIU-p and %△TIU-d were significant factors influencing PFS (p < 0.050). A value of %△TIU-d≤62.19% was associated with negative prognosis [relative risk (RR):2.103; P = 0.021], as was ypN stage (RR:4.250; p = 0.003). CONCLUSION Iodine values (especially the TIU) are noninvasive quantitative parameters that are potentially helpful for evaluating the treatment response and survival prognosis of LAGC after NAC. %△TIU-d represents a strong independent prognostic factor, increasing preoperative risk assessment performance.

A hyperspectral dataset of precancerous lesions in gastric cancer and benchmarks for pathological diagnosis.

Gastric cancer (GC) is one of the most common cancers worldwide. A lot of studies have found that early GC has good prognosis. Unfortunately, the diagnosis rate of early GC is suboptimal due to inadequate disease screening and the insidious nature of early lesions. Pathological diagnosis is usually regarded as the "gold standard" for the diagnosis of GC. However, traditional pathological diagnosis is tedious and time-consuming. With the development of deep learning, computer-aided diagnosis is widely used to assist pathologists for diagnosis. As conventional pathology, diagnosis is based on color images, it is not as informative as hyperspectral imaging, which introduces spectroscopy into imaging techniques. This article combines microscopic hyperspectral image (HSI) with deep learning networks to assist in the diagnosis of precancerous lesions in gastric cancer (PLGC). A large scale microscopic hyperspectral PLGC dataset with 924 effective scenes is built and self-supervised learning is adopted to provide pretrained models for HSI. These pretrained models effectively improve the performance of downstream classification tasks. Furthermore, a symmetrically deep connected network is proposed to train with images from different imaging modalities and improve the diagnostic accuracy to 96.59%.

Expanding the clinical spectrum of adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a heterogeneous neurodegenerative disease with multiple clinical subtypes. Recent breakthroughs on neuroimaging, skin biopsy and genetic testing have facilitated the diagnosis. We aim to investigate the clinical characteristics of Chinese NIID patients to further refine the spectrum. We analyzed the clinical features of 25 NIID patients from 24 unrelated families and performed skin biopsy and/or sural nerve biopsy on 24 probands. Repeat-primed PCR and fluorescence amplicon length PCR were conducted to detect GGC repeats of NOTCH2NLC. Onset age ranged from 24 to 72 years old, and the disease duration ranged from 12 h to 25 years with the mode of onset characterized as acute, recurrent or chronic progressive type. Tremor was a common phenotype, often observed in the early stages, next to dementia and paroxysmal encephalopathy. Symptoms infrequently reported such as oromandibular dystonia, recurrent vomiting, dizziness and headache of unknown origin, as well as pure peripheral neuropathy were also suggestive of NIID. Reversible leukoencephalopathy following encephalitic episodes and the absence of apparent DWI abnormality were noticed. Two genetically confirmed NIID patients failed to be identified intranuclear inclusions, and one patient was simultaneously found significant mitochondrial swelling and fingerprint profiles depositing in lysosomes. All the patients were identified abnormal GGC repeats of NOTCH2NLC. We identify some atypical clinicopathological features and consider that pathological examinations combined with genetic testing is the gold standard for diagnosis. Whether lysosomal and mitochondrial dysfunction is involved in the pathogenesis of NIID deserves further study.

Effects of rehabilitation nursing care on deep vein thrombosis of the lower limbs following spinal fractures.

OBJECTIVE: To explore the preventive effect of rehabilitation nursing care for deep vein thrombosis (DVT) of the lower limbs following spinal fractures, and to analyze its influence on the hemorheology of patients. METHODS: A total of 99 patients with spinal fractures were allocated into a study group (n=50) and control group (n=49), and they were treated with internal fixation plus vertebroplasty. Afterwards, patients in the control group were given routine care and postoperative rehabilitation, and those in the study group received rehabilitation nursing care on the day after surgery, including posture guidance, massage of both lower limbs, and functional training. The functional training was consecutively performed until free movement of the legs was possible. All patients were reexamined after three months. The incidence of low-limb DVT, pain, and swelling, as well as the degree of swelling, hemorheology, quality of life, and patient satisfaction were compared between the two groups. RESULTS: The study group had less frequent low-limb DVT, pain and swelling than the control group (all P<0.05). In the study group, the degree of swelling was significantly reduced, with earlier return to normal activity and shorter hospital stay (all P<0.05). After intervention, plasma viscosity, whole blood low/high shear viscosity and erythrocyte aggregation (EA) decreased in both groups, especially in the study group (all P<0.05). Although GQOL-74 scores increased in both groups, there was a more significant increase that occurred in study group (all P<0.001). Patients in the study group were more satisfied with nursing services than those in the control group (P<0.05). CONCLUSION: Rehabilitation nursing care contributes to the improvement of hypercoagulable states and the prevention of lower-limb DVT for surgically treated patients with spinal fractures, and it is effective in relieving pain and swelling of the lower limbs, thereby enhancing quality of life and patient satisfaction.

Case Report: Temozolomide Treatment of Refractory Prolactinoma Resistant to Dopamine Agonists.

Therapeutic agents for refractory prolactinomas that are resistant to dopamine agonists (DAs) are troublesome, and surgery often only removes a large part of the tumor without complete remission. Among the various second-line treatment regimens, the treatment effect of the alkylating agent temozolomide (TMZ) is only effective for approximately half of patients; however, complete remission is rare. Here we report a patient with prolactinoma who was resistant to high-dose cabergoline (CAB) treatment, demonstrating a continuous increase in both the tumor volume and the prolactin (PRL) level. Given that this case is a refractory prolactinoma, the patient underwent two transsphenoidal approach (TSA) surgeries. The pathological analysis indicated that the Ki-67 index increased significantly from 3% to 30%, and the expression levels of DRD2 and MGMT were low. Finally, TMZ treatment was recommended. A total of six cycles of TMZ standard chemotherapy shrank the tumor volume and the tumor disappeared completely. During the 6-month follow-up period, the tumor did not relapse again, and the PRL level was also normal. RNA sequencing and DNA whole genome sequencing were performed on this prolactinoma specimen, revealing 16 possible gene mutations, including a missense mutation of the PABPC1 gene. Additionally, the copy number variation analysis results showed that several chromosomes had copy number gains compared to the matched peripheral blood sample. In this case, low expression of DRD2 and high proliferation led to resistance to CAB, whereas low MGMT expression contributed to sensitivity to TMZ treatment. The results of genome sequencing still need further investigation at the molecular level to explain the tumor aggressiveness and high sensitivity to TMZ.

Preoperative imaging evaluation of the absolute indication criteria for endoscopic submucosal dissection in early gastric cancer patients.

INTRODUCTION: Gastric cancer (GC) is a common malignant tumor with a high mortality rate. AIM: To determine the accuracy of preoperative imaging information obtained from the combined use of general gastroscopy (GS), endoscopic ultrasonography (EUS), and multi-detector computed tomography (MDCT) regarding absolute indication of endoscopic submucosal dissection (ESD) in early gastric cancer (EGC). MATERIAL AND METHODS: The relationship between clinical features of 794 EGC patients and lymph node metastasis (LNM) was analyzed. Multivariate logistic regression analysis was used to investigate the risk factors for LNM. Additionally, the accuracy of diagnosis of imaging techniques for ESD indications was determined by receiver operating characteristic (ROC) analysis. RESULTS: Data showed that tumor size > 2 cm (p = 0.0071), T1b stage (p < 0.0001), undifferentiated histology (p < 0.0001), and vascular invasion (p = 0.0007) were independent risk factors for LNM in patients with EGC. Indications for ESD have a specificity of 100% for the diagnosis of patients with LNM. Additionally, the diagnostic efficacy of the use of GS, EUS, and MDCT in identifying node positive status, T1a disease, tumor size ≤ 2 cm, and ulceration was found to be moderate with area under the curve (AUC) of receiver operating characteristic curve (ROC) of 0.71, 0.64, 0.72, and 0.68, respectively. Furthermore, the use of imaging techniques for overall indication criteria for ESD had a moderate utility value with an AUC of 0.71. CONCLUSIONS: Our data suggested that, based on the combined use of GS, EUS, and MDCT, a high specificity of patient selection for ESD treatment can be achieved.

NEK2 regulates cellular proliferation and cabergoline sensitivity in pituitary adenomas.

Objective: To identify critical roles played by NEK2 in prolactinomas and to clarify the corresponding underlying mechanisms. Methods: We performed RNA-seq on MMQ cell lines treated with the dopamine receptor agonist cabergoline (CAB) to identify genes involved in prolactinoma progression and dopamine receptor-agonist (DA) sensitivity. NEK2 was then selected for further study. The expression of NEK2 was examined using quantitative real-time PCR, western immunoblotting, and immunohistochemistry - both in pituitary adenomas (PA) and in normal pituitary tissue. We used gain-of-function and loss-of-function assays to explore the biologic roles of NEK2 in cell growth in vivo and in vitro. Co-immunoprecipitation was also used to detect the binding between NEK2 and USP7. Results: Herein, we reported that NEK2 was upregulated in prolactinomas, particularly dopamine-resistant prolactinomas. NEK2 overexpression significantly promoted pituitary tumor GH3 and MMQ cell proliferation, and it impaired cellular sensitivity to CAB. Conversely, knockdown of NEK2 inhibited GH3 and MMQ cell growth, and sensitized the cells to CAB. Mechanistically, NEK2 regulated cell proliferation via the Wnt-signaling pathway; and in addition, we demonstrated that USP7 interacted with, deubiquitylated, and stabilized NEK2. Conclusions: Collectively, our results suggest that NEK2 might be a potential therapeutic target for prolactinoma.

Neoadjuvant FLOT versus SOX phase II randomized clinical trial for patients with locally advanced gastric cancer.

Neoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (FLOT regimen) has shown promising results in terms of pathological response and survival rate in patients with locally advanced resectable gastric cancer (LAGC). However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (SOX regimen) is the preferred chemotherapy regimen in Eastern countries. Here, we conduct an open label, two-arm, phase II randomized interventional clinical trial (Dragon III; ClinicalTrials.gov: NCT03636893) to evaluate the safety and efficacy of both regimens. Patients with LAGC are randomly assigned to receive either 4 cycles of the neoadjuvant FLOT regimen (40 patients) or 3 cycles of the SOX regimen (34 patients) before gastrectomy. The primary endpoint is the comparison of complete (TRG1a) or subtotal (TRG1b) tumor regression grading in the primary tumor. There are no significant differences in adverse effects or postoperative morbidity and mortality between the two groups. No significant differences in the proportion of tumor regression grading between the FLOT group and the SOX group are found. Complete or subtotal TRG is 20.0% in the FLOT group versus 32.4% in the SOX group. Therefore, our study does not find statistically significant differences between neoadjuvant FLOT and SOX regimens for the primary outcomes reported here in locally advanced gastric cancer.

TRPV4 Overexpression Promotes Metastasis Through Epithelial-Mesenchymal Transition in Gastric Cancer and Correlates with Poor Prognosis.

PURPOSE: Transient receptor potential vanilloid 4 (TRPV4) has been reported to be involved in the progression of several human tumors. Nevertheless, clinical significance and molecular mechanism of TRPV4 in gastric cancer (GC) remain poorly defined. PATIENTS AND METHODS: Immunohistochemistry assays were used to investigate the correlation between the expression of TRPV4 and epithelial-mesenchymal transition (EMT) markers in human GC tissues. The correlations between TRPV4 expression and clinicopathological features and between TRPV4 expression and survival rates were also examined. TRPV4 knockdown was performed by using small interfering RNAs. In vitro, Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and transwell assay were employed to further explore the biological functions of TRPV4, and Western blotting was used to evaluate the changes in the expression of TRPV4 protein and EMT-related proteins in HGC-27 and MGC-803 human GC cell lines. RESULTS: TRPV4 expression was upregulated in GC tissues and cell lines. TRPV4 overexpression was associated with greater depth of tumor invasion, lymph node metastasis, higher TNM stage, poor overall survival, and worse disease-free survival. TRPV4 expression was inversely correlated with E-cadherin expression and positively correlated with vimentin expression. In vitro, knockdown of TRPV4 inhibited GC cell proliferation, colony formation, and invasion. Furthermore, the knockdown of TRPV4 modulated EMT by upregulating E-cadherin expression and downregulating the expression of N-cadherin and vimentin. In addition, the EMT-related transcription factor Snail was downregulated, whereas the expression levels of other transcription factors such as Slug and Twist did not change. CONCLUSION: TRPV4 was upregulated in human GC and the overexpression of TRPV4 could promote GC progression, partially through Snail-mediated EMT.