TRIANGLE operation, combined with adequate adjuvant chemotherapy, can improve the prognosis of pancreatic head cancer: A retrospective study.

BACKGROUND: The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein, celiac axis-common hepatic artery, and superior mesenteric artery to improve patient prognosis. Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy (PD). AIM: To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC. METHODS: This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023, with or without the TRIANGLE operation. Patients were divided into the PDTRIANGLE and PDnon-TRIANGLE groups. Surgical and survival outcomes were compared between the two groups. Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy ≥ 6 months. RESULTS: The PDTRIANGLE and PDnon-TRIANGLE groups included 52 and 55 patients, respectively. There were no significant differences in the baseline characteristics or perioperative indexes between the two groups. Furthermore, the recurrence rate was lower in the PDTRIANGLE group than in the PDnon-TRIANGLE group (48.1% vs 81.8%, P < 0.001), and the local recurrence rate of PDAC decreased from 37.8% to 16.0%. Multivariate Cox regression analysis revealed that PDTRIANGLE (HR = 0.424; 95%CI: 0.256-0.702; P = 0.001), adequate adjuvant chemotherapy ≥ 6 months (HR = 0.370; 95%CI: 0.222-0.618; P < 0.001) and margin status (HR = 2.255; 95%CI: 1.252-4.064; P = 0.007) were found to be independent factors for the recurrence rate. CONCLUSION: The TRIANGLE operation is safe for PDAC patients undergoing PD. Moreover, it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

Effects of brief mindfulness training on smoking cue-reactivity in tobacco use disorder: Study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of Tobacco Use Disorder (TUD) represents a significant and pressing global public health concern, with far-reaching and deleterious consequences for individuals, communities, and healthcare systems. The craving caused by smoking cue is an important trigger for relapse, fundamentally hindering the cessation of cigarette smoking. Mindfulness interventions focusing on cue-reactivity was effective for the treatment of related dependence. Brief mindfulness training (BMT) meets the short-term needs for intervention but the effects still need to be examined. The objective of the present study is to investigate the impact of BMT intervention on smoking cue-reactivity among Chinese college students with TUD, to uncover the dynamic models of brain function involved in this process. METHOD: A randomized control trial (RCT) based on electroencephalography (EEG) was designed. We aim to recruit 90 participants and randomly assign to the BMT and control group (CON) with 1:1 ratio. A brief mindfulness training will be administered to experimental group. After the intervention, data collection will be conducted in the follow-up stage with 5 timepoints of assessments. EEG data will be recorded during the smoking cue-reactivity task and 'STOP' brief mindfulness task. The primary outcomes include subjective reports of smoking craving, changes in EEG indicators, and mindfulness measures. The secondary outcomes will be daily smoking behaviours, affect and impulsivity, as well as indicators reflecting correlation between mindfulness and smoking cue-reactivity. To evaluate the impact of mindfulness training, a series of linear mixed-effects models will be employed. Specifically, within-group effects will be examined by analysing the longitudinal data. Additionally, the effect size for all statistical measurements will be reported, offering a comprehensive view of the observed effects. DISCUSSION: The current study aims to assess the impact of brief mindfulness-based intervention on smoking cue-reactivity in TUD. It also expected to enhance our understanding of the underlying processes involved in brain function and explore potential EEG biomarkers at multiple time points. TRIAL REGISTRATION: Trial registration number: ChiCTR2300069363, registered on 14 March 2023. Protocol Version 1.0., 10 April 2023.

Insecure Attachment and Depressive Symptoms among a Large Sample of Chinese Young Adults: The Mediating Role of Positive and Negative Self-Compassion.

OBJECTIVE: The present study aimed to explore the relationship between insecure attachment (attachment anxiety and avoidance) and depressive symptoms in Chinese young adults as well as the mediating roles of positive and negative self-compassion. METHODS: An online survey was administered among college students in mainland China. This involved their completion of questionnaires encompassing socio-demographic details, attachment anxiety, attachment avoidance, self-compassion, and depressive symptoms. RESULTS: Attachment anxiety and avoidance exhibited connections with depressive symptoms through increased negative self-compassion and decreased positive self-compassion. Attachment anxiety was associated with depressive symptoms primarily through the mediating effect of negative self-compassion. Conversely, attachment avoidance was related to depressive symptoms mainly through the mediating role of positive self-compassion. CONCLUSIONS: Attachment anxiety exerted a slightly stronger influence on negative self-compassion, whereas attachment avoidance exhibited a more prominent impact on positive self-compassion. Despite these differences, both attachment styles were comparable in their overall influence on depressive symptoms. This revelation provides fresh insights into the relationship between insecure attachment and depressive symptoms among young adults, underscoring the importance for intervention program development.

Serum ferritin and neutrophil-to-lymphocyte ratio predict all-cause mortality in patients receiving maintenance hemodialysis: a prospective study.

Introduction: Maintenance hemodialysis is an effective treatment for end-stage renal disease patients. A critical factor contributing to the deterioration and death of maintenance hemodialysis patients is inflammation. Therefore, we focused on two inflammatory markers, serum ferritin and neutrophil-to-lymphocyte ratio, to speculate whether they could predict the prognosis of maintenance hemodialysis patients. Patients and methods: We followed 168 patients with maintenance hemodialysis from July 2019 to July 2022 with the endpoint of all-cause death or follow-up completion. Receiver operating characteristic curves were plotted to assess the values of serum ferritin, neutrophil-to-lymphocyte ratio and serum ferritin combined with neutrophil-to-lymphocyte ratio to predict the outcomes of maintenance hemodialysis patients. Kaplan-Meier survival curves were constructed to compare survival rates over time. Results: Receiver operating characteristic curves demonstrated that the best cut-off value of serum ferritin for predicting the prognosis of maintenance hemodialysis patients was 346.05 µg/L, and that of neutrophil-to-lymphocyte ratio was 3.225. Furthermore, a combination of both had a more excellent predicting value than either index (p < 0.05). Kaplan-Meier survival curve analyses revealed that low serum ferritin levels and low neutrophil-to-lymphocyte ratio had a higher probability of survival than high ferritin levels and high neutrophil-to-lymphocyte ratio, separately. Conclusion: Elevated serum ferritin and neutrophil-to-lymphocyte ratio are closely related to all-cause mortality among maintenance hemodialysis patients, for which they may be predictors of all-cause mortality. Additionally, the combination of the two has a much higher predictor value for the prognosis of maintenance hemodialysis patients.

Tucidinostat Plus Exemestane as a Neoadjuvant in Early-Stage, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

BACKGROUND: To assess the efficacy and safety of tucidinostat plus exemestane as a neoadjuvant strategy in early-stage breast cancer. METHODS: This prospective, open-label, single-arm phase II trial enrolled patients with stage II-III breast cancer with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative. Eligible patients received tucidinostat plus exemestane, and then breast-conserving surgery (BCS) or modified radical mastectomy. RESULTS: Among 20 enrolled patients, 3 of them achieved preoperative endocrine prognostic index (PEPI) score of 0. Additionally, complete cell cycle arrest was observed in 7, radiologic objective response rate in 10, and disease control rate in 20 patients, pathological complete response in 1 patient, and 5 patients performed BCS. Ki67 suppression from baseline to surgery was observed in 17 of patients, with the Ki67 change ratio of -73.5%. Treatment-emergent adverse event included neutropenia, leukopenia, thrombocytopenia, lymphopenia, hypoalbuminemia, aspartate aminotransferase elevation, glutamyl transpeptidase elevation, anemia, and alanine aminotransferase elevation. CONCLUSIONS: Despite the rate of PEPI score 0 was not high, tucidinostat plus exemestane as a neoadjuvant therapy might be well tolerated and showed promising clinical responses in patients with early hormone receptor-positive, HER2-negative breast cancer. To clarify the safety and efficacy of this strategy, further investigation is warranted. CLINICAL TRIAL REGISTRATION: ChiCTR2100046678.

HHLA2 is more significantly associated with poor prognosis in TSCC than PD-L1.

BACKGROUND: The incidence and mortality of tongue squamous cell carcinoma have shown an alarming increase in recent years. This study aimed to investigate the potential of HHLA2 as an immune checkpoint in comparison to PD-L1. METHODS: We obtained RNA-seq data from TCGA to study HHLA2 and PD-L1 expression across various tissues. Using the CIBERSORT package, we estimated cell type abundances within mixed populations based on gene expression profiles. Immunohistochemistry was performed to analyze HHLA2 and PD-L1 expression in Tongue squamous cell carcinoma. Prognostic evaluation was carried out with Kaplan-Meier curves and the log-rank test. To explore factors affecting HHLA2, univariate and multivariate Cox regression analyses were conducted with the COX regression model. Additionally, we used single-cell RNA sequencing data from the GEO database for gene set enrichment analysis with genes strongly correlated with HHLA2. RESULTS: Our analysis of RNA-seq data unveiled a significant upregulation of HHLA2 and PD-L1 expression in primary tumors when compared with normal tissue. HHLA2 exhibited a positive expression rate of 36.9%, while PD-L1 had a positive expression rate of 24.6%. HHLA2 emerged as a noteworthy independent risk factor impacting the overall survival of Tongue squamous cell carcinoma patients. The analysis of scRNA-seq data shed light on the involvement of HHLA2 in key pathways related to cell cycle regulation and interferon alpha/beta signaling. CONCLUSIONS: This study suggests that in the context of Tongue squamous cell carcinoma, HHLA2 may represent a more promising target for immunotherapy when compared with PD-L1.

Clinical characteristics and prognosis analysis of postoperative patients with stage I-III colon cancer based on SEER database.

PURPOSE: To identify the relevant factors affecting the prognosis and survival time of colon cancer and construct a survival prediction model. METHODS: Data on postoperative stage I-III colon cancer patients were obtained from the Surveillance, Epidemiology, and End Results database. We used R project to analyze the data. Univariate and multivariate Cox regression analyses were performed for independent factors correlated with overall survival from colon cancer. The C-index was used to screen the factors that had the greatest influence in overall survival after surgery in colon cancer patients. Receiver operating characteristic (ROC) curve was made according to the Risk score and calculated to validate the predictive accuracy of the model. In addition, we used decision curve analysis (DCA) to evaluate the clinical benefits and utility of the nomogram. We created a model survival curve to determine the difference in prognosis between patients in the low-risk group and those in the high-risk group. RESULTS: Univariate and multifactor COX analyses showed that the race, Grade, tumor size, N-stage and T-stage were independent risk factors affecting survival time of patients. The analysis of ROC and DCA showed the nomogram prediction model constructed based on the above indicators has good predictive effects. CONCLUSION: Overall, the nomogram constructed in this study has good predictive effects. It can provide a reference for future clinicians to evaluate the prognosis of colon cancer patients.

Impact of the COVID-19 Pandemic on the Professional Attitudes of Medical Students: A Pre-Post-Like Study.

OBJECTIVE: This study assesses the difference in professional attitudes among medical students, both before and after coronavirus disease 2019 (COVID-19), and identifies the determinants closely associated with it, while providing precise and scientific evidence for implementing precision education on such professional attitudes. METHODS: A pre-post-like study was conducted among medical students in 31 provinces in mainland China, from March 23, to April 19, 2021. RESULTS: The proportion of medical students whose professional attitudes were disturbed after the COVID-19 pandemic, was significantly lower than before the COVID-19 pandemic (χ2 = 15.6216; P < 0.0001). Compared with the "undisturbed -undisturbed" group, the "undisturbed-disturbed" group showed that there was a 1.664-fold risk of professional attitudes disturbed as grade increased, 3.269-fold risk when others suggested they choose a medical career rather than their own desire, and 7.557-fold risk for students with COVID-19 in their family, relatives, or friends; while the "disturbed-undisturbed" group showed that students with internship experience for professional attitudes strengthened was 2.933-fold than those without internship experience. CONCLUSIONS: The professional attitudes of medical students have been strengthened during the COVID-19 pandemic. The results provide evidence of the importance of education on professional attitudes among medical students during public health emergencies.

Preservation of the pectoralis major fascia has no impact on the long-term oncologic outcomes of patients with breast cancer treated with conservative mastectomy and immediate breast reconstruction: A propensity score matching analysis.

BACKGROUND: The oncologic safety of preserving the pectoralis major fascia (PMF) in patients with breast cancer remains controversial. In this study, we aimed to determine the impact of preserving the PMF on long-term oncologic outcomes in patients with breast cancer treated with immediate implant-based breast reconstruction (IBBR) following conservative mastectomy. METHODS: We selected women with early-stage breast cancer who underwent conservative mastectomy and submuscular IBBR in our center during 2014-2019. The propensity score matching method was used to create well-balanced fascia-preserved and fascia-removed groups. Locoregional recurrence-free survival (LRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the fascia-preserved and fascia-removed groups. RESULTS: After matching, there were 219 patients in each group. The mean follow-up time was 64.8 ± 18.1 months for the fascia-preserved group and 64.9 ± 18.4 months for the fascia-removed group. There were no significant differences between the groups in terms of LRFS (91.3% vs. 93.8%; p = 0.818), DMFS (94.0% vs. 92.3%; p = 0.056), DFS (89.9% vs. 88.4%; p = 0.261), and OS (95.8% vs. 95.4%; p = 0.783) rates. In the fascia-preserved group, 61.5% of the locoregional recurrence events occurred within 2 years after surgery. CONCLUSION: Preservation of the PMF did not significantly impact the long-term oncologic outcomes in patients with breast cancer who underwent conservative mastectomy and IBBR. The PMF might be safely preserved in patients without suspicious tumor invasion into this fascia.

A study related to the treatment of gastric cancer with Xiang-Sha-Liu-Jun-Zi-Tang based on network analysis.

Purpose: Xiang-Sha-Liu-Jun-Zi-Tang(XSLJZT) is a common formula for the treatment of Gastric Cancer(GC) and is widely used in clinical practice, however, there is a lack of investigation into its mechanism. Methods: We collected and organized drug and disease targets, constructed the "XSLJZT-Active Ingredient-Target" visualization network, and performed GO and KEGG functional enrichment analysis of crossover genes, followed by molecular docking of active ingredients and core targets. The best docked monomers were combined with weighted gene co-expression network analysis(WGCNA) and macroscopically analyzed by GO and KEGG enrichment techniques. The results of cluster gene difference analysis, ROC evaluation, and CIBERSORT immune infiltration analysis were evaluated and finally supported by cellular experiments. Results: The main components of XSLJZT are quercetin, stigmasterol, and naringenin, effectively treat GC by targeting STAT3, TP53 and MAPK3, which are involved in IL-17, TNF and HIF-1 signaling pathways. The results of molecular docking showed that quercetin bound better to the core targets. We performed an in-depth analysis of this monomer and found that quercetin acts on the core targets of TP53, MMP9, TIMP1 and MYC, and is involved in two key signaling pathways, TNF and IL-17, thus effectively treating GC. The experimental results are consistent with our analysis that quercetin inhibits the proliferation of GC cells and promotes apoptosis, and TP53, MYC and TIMP1 are the quercetin targets for the treatment of GC. Conclusion: The present study tentatively suggests that quercetin, the main active ingredient in XSLJZT, can exert a therapeutic effect on GC by targeting TIMP1.

Prognostic significance of preoperative lymphocyte to monocyte ratio in patients with signet ring gastric cancer.

BACKGROUND: The ratio of lymphocytes to monocytes (LMR) has been shown to be an effective predictor of gastric cancer prognosis. However, its predictive accuracy for signet ring gastric cancer is currently not well understood. AIM: To evaluate the prognosis predictive accuracy of preoperative LMR in signet ring gastric cancer. METHODS: A total of 212 signet ring gastric cancer patients admitted at the Xiangya Hospital of Central South University, Department of Gastrointestinal Surgery, from January 2012 to December 2016 were enrolled in the study. The prognosis predictive accuracy of preoperative LMR was explored based on the area under the receiver operating characteristic. Factors that significantly affect the survival of patients were identified using single factor analysis, and those that were independently associated with signet ring gastric cancer were identified through multivariate analysis. RESULTS: The results of the single factor analysis revealed a strong correlation between the survival of signet ring gastric cancer patients and several factors, including tumor invasion (χ2 = 49.726; P < 0.001), lymph node metastasis (χ2 = 30.269; P < 0.001), pTNM stage (χ2 = 49.322; P < 0.001), surgical approach (χ2 = 8.489; P = 0.004), age (t = -2.213; P < 0.028), carcinoembryonic antigen (CEA) (Z = -3.265; P = 0.001), platelet-to-lymphocyte ratio (Z = -2.196; P = 0.028), LMR (Z = -2.226; P = 0.026), ALB (t = 3.284; P = 0.001), prognostic nutritional index (t = -3.789; P < 0.001) and FIB (Z = -3.065; P = 0.002). Furthermore, the multivariate analysis further demonstrated that age (HR: 0.563, 95%CI: 0.363-0.873), tumor invasion depth (HR: 0.226, 95%CI: 0.098-0.520), pTNM stage (HR: 0.444, 95%CI: 0.255-0.771), preoperative CEA level (HR: 0.597, 95%CI: 0.386-8.790), and preoperative LMR level (HR: 1.776, 95%CI: 1.150-2.741) were independent factors influencing the prognosis of signet ring gastric cancer. CONCLUSION: In signet ring gastric cancer patients, a low preoperative LMR level predicts poor prognosis. The death risk ratio of the low LMR group compared to the high LMR group is 1.776.

Social support and prosocial behavior in Chinese college students during the COVID-19 outbreak: a moderated mediation model of positive affect and parental care.

Purpose: Prosocial behavior (PSB) plays a critical role in everyday society, especially during the pandemic of COVID-19. Understanding the underlying mechanism will provide insight and advance its implementation. According to the theory of PSB, social interaction, family and individual characters all contribute to its development. The current study aimed to investigate the influencing factor of PSB among Chinese college students during COVID-19 outbreak. This is an attempt to understand the mechanism of PSB and to provide a reference for the formulation of policies aimed at promoting healthy collaborative relationships for college students. Method: The online questionnaire was administered to 664 college students from 29 provinces of China via Credamo platform. There were 332 medical students and 332 non-medical students aged between 18 and 25 included for final study. The mediating role of positive emotion/affect (PA) and the moderating role of parental care in the association between social support and PSB during the pandemic of COVID-19 was explored by using Social Support Rate Scale (SSRS), Prosocial Tendencies Measurement Scale (PTM), The Positive and Negative Affect (PANAS), as well as Parental Bonding Instrument (PBI). The process macro model of SPSS was adopted for mediating and moderating analysis. Results: The results showed that social support positively predicted PSB among Chinese college students, even after adding PA as a mediation variable. PA during COVID-19 mediated the association between social support and PSB. PSB also revealed as a predictor of PA by regression analysis. Moreover, the moderating effect of parental care in the relationship between PA and PSB was detected. Conclusion: PA under stress acts as a mediator between social support and PSB. This mediating effect was moderated by PC in childhood. In addition, PSB was observed to predict PA reversely. The promoting factors and path between the variables of PSB are complex and need to be explored extensively. The underlying factors and process should be further investigated for the development of intervention plans.

Predicting pathological complete response after neoadjuvant chemotherapy: A nomogram combining clinical features and ultrasound semantics in patients with invasive breast cancer.

Background: Early identification of response to neoadjuvant chemotherapy (NAC) is instrumental in predicting patients prognosis. However, since a fixed criterion with high accuracy cannot be generalized to molecular subtypes, our study first aimed to redefine grades of clinical response to NAC in invasive breast cancer patients (IBC). And then developed a prognostic model based on clinical features and ultrasound semantics. Methods: A total of 480 IBC patients were enrolled who underwent anthracycline and taxane-based NAC between 2018 and 2020. The decrease rate of the largest diameter was calculated by ultrasound after NAC and their cut-off points were determined among subtypes. Thereafter, a nomogram was constructed based on clinicopathological and ultrasound-related data, and validated using the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and clinical impact curve (CIC). Results: The optimal cut-off points for predicting pCR were 53.23%, 51.56%, 41.89%, and 53.52% in luminal B-like (HER2 negative), luminal B-like (HER2 positive), HER2 positive, and triple-negative, respectively. In addition, time interval, tumor size, molecular subtypes, largest diameter decrease rate, and change of blood perfusion were significantly associated with pCR (all p < 0.05). The prediction model based on the above variables has great predictive power and clinical value. Conclusion: Taken together, our data demonstrated that calculated cut-off points of tumor reduction rates could be reliable in predicting pathological response to NAC and developed nomogram predicting prognosis would help tailor systematic regimens with high precision.

Syncope as the initial symptom in a patient with nasopharyngeal carcinoma: a case report.

BACKGROUND: A high prevalence of nasopharyngeal carcinoma (NPC) has been found in China, but it rarely occurs with syncope. Studies have demonstrated that syncope due to NPC may be related to carotid sinus syndrome, glossopharyngeal irritation, and parapharyngeal and retropharyngeal space lesions. Such patients require evaluation by nasopharyngoscopy and head magnetic resonance imaging/computed tomography. There is no known single effective treatment for these patients. Various interventions may be considered in an effort to relieve syncope, including vasoconstrictive drugs, cardiac pacemaker implantation, radiotherapy and chemotherapy, and surgical resection. CASE PRESENTATION: This case report describes a 56-year-old man who developed recurrent syncope with atrial fibrillation, a long RR interval, and hypotension. A single chamber pacemaker was fitted, but it failed to relieve the symptom. Cranial magnetic resonance imaging and pathological tests led to a final diagnosis of NPC. After six courses of chemotherapy and 35 sessions of radiotherapy, the patient became asymptomatic. However, he died from a massive uncontrolled hemorrhage in the nasopharynx two years later. CONCLUSIONS: This case brings attention to the fact that syncope can be a symptom of NPC. Due to the insidiously malignant nature of this cancer, when a patient presents with syncope, clinicians should bear in mind this connection, albeit a rare one. There are at least two ways of treating NPC-associated syncope, but there is disagreement about which is the most effective.

A community-based cross-sectional study of anxiety and metabolic syndrome.

BACKGROUND: The prevalence of anxiety and other psychological disorders has increased during the COVID-19 pandemic, especially among the elderly. Anxiety and metabolic syndrome (MetS) may aggravate each other. This study further clarified the correlation between the two. METHODS: Adopting a convenience sampling method, this study investigated 162 elderly people over 65 years of age in Fangzhuang Community, Beijing. All participants provided baseline data on sex, age, lifestyle, and health status. The Hamilton Anxiety Scale (HAMA) was used to assess anxiety. Blood samples, abdominal circumference, and blood pressure were used to diagnose MetS. The elderly were divided into MetS and control groups according to the diagnosis of MetS. Differences in anxiety between the two groups were analysed and further stratified by age and gender. Multivariate logistic regression analysis was used to analyse the possible risk factors for MetS. RESULTS: Compared with the control group, anxiety scores of the MetS group were statistically higher (Z = 4.78, P < 0.001). There was a significant correlation between anxiety levels and MetS (r = 0.353, P < 0.001). Multivariate logistic regression revealed that anxiety (possible anxiety vs no anxiety: odds ratio [OR] = 2.982, 95% confidence interval [CI] 1.295-6.969; definite anxiety vs no anxiety: OR = 14.573, 95%CI 3.675-57.788; P < 0.001) and BMI (OR = 1.504, 95% CI 1.275-1.774; P < 0.001) were possible risk factors for MetS. CONCLUSION: The elderly with MetS had higher anxiety scores. Anxiety may be a potential risk factor for MetS, which provides a new perspective on anxiety and MetS.

CMTM7 inhibits breast cancer progression by regulating Wnt/ß-catenin signaling.

BACKGROUND: Breast cancer is the major cause of death in females globally. Chemokine-like factor like MARVEL transmembrane domain containing 7 (CMTM7) is reported as a tumor suppressor and is involved in epidermal growth factor receptor degradation and PI3K/AKT signaling in previous studies. However, other molecular mechanisms of CMTM7 remain unclear. METHODS: The expression level of CMTM7 in breast cancer cells and tissues was detected by qRT-PCR and western blot, and the methylation of CMTM7 promoter was detected by BSP sequencing. The effect of CMTM7 was verified both in vitro and in vivo, including MTT, colony formation, EdU assay, transwell assay and wound healing assay. The interaction between CMTM7 and CTNNA1 was investigated by co-IP assay. The regulation of miR-182-5p on CMTM7 and TCF3 on miR-182-5p was detected by luciferase reporter assay and ChIP analysis. RESULTS: This study detected the hypermethylation levels of the CMTM7 promoter region in breast cancer tissues and cell lines. CMTM7 was performed as a tumor suppressor both in vitro and in vivo. Furthermore, CMTM7 was a direct miR-182-5p target. Besides, we found that CMTM7 could interact with Catenin Alpha 1 (CTNNA1) and regulate Wnt/ß-catenin signaling. Finally, transcription factor 3 (TCF3) can regulate miR-182-5p. We identified a feedback loop with the composition of miR-182-5p, CMTM7, CTNNA1, CTNNB1 (ß-catenin), and TCF3, which play essential roles in breast cancer progression. CONCLUSION: These findings reveal the emerging character of CMTM7 in Wnt/ß-catenin signaling and bring new sights of gene interaction. CMTM7 and other elements in the feedback loop may serve as emerging targets for breast cancer therapy.

HER2-low-positive and response to NACT and prognosis in HER2-negative non-metastatic BC.

PURPOSE: With the release of promising data from clinical trials of novel anti-HER2 antibody-drug conjugates, there is a new therapeutic direction in HER2-low expression breast cancer (BC). This study aims to evaluate the differences in clinicopathological characteristics of HER2-low-positive and HER2-zero BC, including response to neoadjuvant chemotherapy (NACT) and prognosis. METHODS: Records of HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients who received NACT at our cancer center between January 2017 and December 2017 were retrospectively collected. HER2-low-positive was defined as immunohistochemistry (IHC) 1 + or IHC2 + /in-situ hybridization negative and HER2-zero was defined as IHC0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) and overall survival (OS) between the two groups. Univariate and multivariable logistic regression models and Cox-proportional hazards models were performed for analysis of the endpoints pCR, RFS, and OS. RESULTS: A total of 239 [84.5%] of 283 tumors were HER2-low-positive (including 132 [55.2%] HER2-1 + and 107 [44.8%] HER2-2 + /ISH non-amplified) and 44 [15.5%] were HER2-zero. Patients in the HER2-low-positive group had more commonly hormone receptor positivity than HER2-zero patients (188 [78.7%] vs. 19 [43.2%], P = 0.000), but there was no difference between HER2-1 + and HER2-2 + / ISH non-amplified (99 [75.0%] vs. 89 [83.2%], P = 0.125). HER2-zero tumors had a significantly higher pCR rate than HER2-low-positive tumors (15 [34.1%] of 44 vs. 22 [9.2%] of 239, P = 0.000). Pathological complete response was also significantly higher in HER2-zero tumors versus HER2-low-positive tumors in the hormone receptor-negative subgroup (13 [52.0%] of 25 vs. 14 [27.5%] of 51, P = 0.036), but not in the hormone receptor-positive subgroup (2 [10.5%] of 19 vs 8 [4.3%] of 188, P = 0.231). No significant difference was observed in 5-year RFS between the two groups (HR 0.577, 95% CI 0.298-1.118, P = 0.103). However, HER2-low-positive tumors showed significantly better OS than HER2-zero tumors (HR 0.280, 95% CI 0.122-0.697, P = 0.006). CONCLUSIONS: These results suggest that HER2-low-positive tumors have specific biological characteristics according to the hormone receptor status and exhibit different responses to NACT and prognosis.

Analysis of genomic and immune intratumor heterogeneity in linitis plastica via multiregional exome and T-cell receptor sequencing.

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole-exome sequencing (WES) and T-cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6339 non-silent mutations from multi-samples, with a median tumor mutation burden (TMB) of 3.30 mutations per Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas (TCGA) cohort (P = 0.53). An extremely high level of genomic ITH was observed, with only 12.42%, 5.37%, 5.35%, and 30.67% of mutations detectable across 10 regions within the same tumors of each patient, respectively. TCR sequencing revealed that TCR clonality was substantially lower in LP than in multi-cancers. IHC using antibodies against CD4, CD8, and PD-L1 demonstrated scant T-cell infiltration in the four LP tumors. Furthermore, profound TCR ITH was observed in all LP tumors, with no T-cell clones shared across tumor regions in any of the patients, while over 94% of T-cell clones were restricted to individual tumor regions. The Morisita overlap index (MOI) ranged from 0.21 to 0.66 among multi-regions within the same tumors, significantly lower than that of lung cancer (P = 0.002). Our results show that LP harbored extremely high genomic and TCR ITH and suppressed T-cell infiltration, suggesting a potential contribution to the frequent recurrence and poor therapeutic response of this adenocarcinoma.

Mutational separation and clinical outcomes of TP53 and CDH1 in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a deadly tumor with the fifth highest occurrence and highest global mortality rates. Owing to its heterogeneity, the underlying mechanism of GC remains unclear, and chemotherapy offers little benefit to individuals. AIM: To investigate the clinical outcomes of TP53 and CDH1 mutations in GC. METHODS: In this study, 202 gastric adenocarcinoma tumor tissues and their corresponding normal tissues were collected. A total of 490 genes were identified using target capture. Through t-test and Wilcoxon rank-sum test, somatic mutations, microsatellite instability, and clinical statistics, including overall survival, were detected, compared, and calculated. RESULTS: The mutation rates of 32 genes, including TP53, SPEN, FAT1, and CDH1 exceeded 10%. TP53 mutations had a slightly lower overall occurrence rate (33%). The TP53 mutation rate was significantly higher in advanced stages (stage III/IV) than that in early stages (stage I/II) (P < 0.05). In contrast, CDH1 mutations were significantly associated with diffuse GC. TP53 is related to poor prognosis of advanced-stage tumors; nevertheless, CDH1 corresponds to a diffuse type of cancer. TP53 is exclusively mutated in CDH1 and is primarily affected by two distinct GC mechanisms. CONCLUSION: Different somatic mutation patterns in TP53 and CDH1 indicate two major mechanisms of GC.