YAP1 suppression by ZDHHC7 is associated with ferroptosis resistance and poor prognosis in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC), which has unique clinical characteristics, arises from benign endometriotic cysts, forming an oxidative stress environment due to excess iron accumulation, and exhibits poor prognosis, particularly in advanced stages owing to resistance to conventional therapeutics. Ferroptosis is an iron-dependent form of programmed cell death induced by lipid peroxidation and controlled by Hippo signaling. We hypothesized that overcoming ferroptosis resistance is an attractive strategy because OCCC acquires oxidative stress resistance during its development and exhibits chemoresistant features indicative of ferroptosis resistance. This study aimed to determine whether OCCC is resistant to ferroptosis and clarify the mechanism underlying resistance. Unlike ovarian high-grade serous carcinoma cells, OCCC cells were exposed to oxidative stress. However, OCCC cells remained unaffected by lipid peroxidation. Cell viability assays revealed that OCCC cells exhibited resistance to the ferroptosis inducer erastin. Moreover, Samroc analysis showed that the Hippo signaling pathway was enriched in OCCC cell lines and clinical samples. Furthermore, patients with low expression of nuclear Yes-associated protein 1(YAP1) exhibited a significantly poor prognosis of OCCC. Moreover, YAP1 activation enhanced ferroptosis in OCCC cell lines. Furthermore, suppression of zinc finger DHHC-type palmitoyltransferase 7 (ZDHHC7) enhanced ferroptosis by activating YAP1 in OCCC cell lines. Mouse xenograft models demonstrated that ZDHHC7 inhibition suppressed tumor growth via YAP1 activation by erastin treatment. In conclusion, YAP1 activation regulated by ZDHHC7 enhanced ferroptosis in OCCC. Thus, overcoming ferroptosis resistance is a potential therapeutic strategy for OCCC.

Investigation of the clinical implications of anterior cervical invasion in locally advanced cervical squamous cell carcinoma.

PURPOSES: This study investigates the clinical significance of the anterior parametrical invasion in surgically treated patients with cervical squamous cell carcinoma (SCC). METHODS: We included patients diagnosed with cervical SCC with local lesions classified as T2b, who were treated at our department between January 2006 and December 2020. We evaluated the degree of anterior invasion using pretreatment magnetic resonance imaging and divided patients into three groups: partial, equivocal, and full invasion. The frequency of recurrence within 3 years (early recurrence) and overall prognosis were assessed. RESULTS: There were 12, 24, and 46 cases in the partial equivocal, and full invasion groups, respectively. Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy was the mainstay of treatment across all groups (7, 17, and 27 cases, respectively). Although the frequency of early recurrence tended to be worse in the full group (partial; 2/7 cases, equivocal; 3/17 cases and full; 9/27 cases), all early local recurrence cases in the full group (four cases) responded well to the subsequent treatment. As for overall survival, the full invasion group had the best prognosis among the three groups. CONCLUSIONS: In surgical treatment, although full anterior invasion may increase the risk of early local recurrence, it was considered to have little prognostic impact.

Incidence of and Risk Factors for Reoperation and Revision Following Total Elbow Arthroplasty with an Anatomic Convertible Prosthesis.

BACKGROUND: Total elbow arthroplasty (TEA) remains a valuable tool for treating inflammatory, degenerative, and traumatic elbow conditions. This study aimed to understand the incidence of and risk factors for reoperation following TEA at a high-volume center utilizing an implant with a convertible linkage and the potential for anatomic lateral column reconstruction. METHODS: All patients undergoing primary TEA with the Latitude prosthesis (Stryker) from July 2001 to May 2020 were identified. Patient characteristics, the surgical indication, and implant characteristics were obtained. Additionally, the indications and timing were identified for reoperations. Postoperative radiographs were analyzed to assess cement quality, implant position, lateral column reconstruction, and distal humeral bone loss. RESULTS: Two hundred and nineteen TEAs were performed in 206 patients; 162 (74.0%) were in female patients, the mean patient age was 61 years (range, 23 to 95 years), and the mean follow-up was 11.8 years (range, 2 to 21 years). The most common indication for surgery was sequelae of trauma (36%). Ninety elbows (41.1%) required 200 reoperations at a mean of 19.6 months. Forty TEAs (18.3%) required revision of nonmodular implants, with 14 (6.4%) undergoing definitive explantation. The 5 and 10-year survivorship was 86.1% and 79.7%, respectively. The most common of the reasons for revision was aseptic loosening (53.8%), and the most common cause for non-revision reoperation was infection (23%). Younger age and greater follow-up duration were associated with greater revision and reoperation risks. Aseptic ulnar loosening was associated with a short ulnar stem length and component linkage (30% of short linked ulnar stems loosened; p < 0.001). Aseptic humeral loosening was associated with less-than-adequate cement-mantle quality (p = 0.04). CONCLUSIONS: Extended follow-up of the Latitude prosthesis at a high-volume center demonstrates that TEA continues to be hampered by a high reoperation rate, primarily due to infection and aseptic loosening. Technical factors such as good cement-mantle quality, longer stem length, and unlinked implants may play a role in preventing aseptic loosening. Further work is required to optimize long-term outcomes following TEA through improved understanding of appropriate surgical indications, techniques, and implant utilization. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

MRI features of ovarian teratomas with somatic-type malignancy and mature cystic teratomas.

PURPOSE: We evaluated the magnetic resonance imaging (MRI) features of ovarian teratomas with somatic-type malignancy (TSMs) and benign ovarian mature cystic teratomas (MCTs) to determine the diagnostic contribution of the MRI findings for differentiating these two teratomas. METHODS: We compared the MRI findings between ovarian TSMs (n = 10) and MCTs (n = 193), and we conducted a receiver operating characteristic (ROC) analysis to determine the MRI findings' contribution to the differentiation of TSMs from MCTs. RESULTS: The maximum diameters of whole lesion and the largest solid component in the TSMs were larger than those of the MCTs (p = 0.0001 and p < 0.0001, respectively). Fat tissue in solid components was seen in 73/116 (62.9%) MCTs but in none of the TSMs (p = 0.0001). Ring-like enhancement in solid components was seen in 60/116 (51.7%) MCTs and none of the TSMs (p = 0.0031). On dynamic contrast-enhanced MRI (DCE MRI), all of the solid components in the TSMs showed a high- or intermediate-risk time intensity curve (TIC), and those in 113 of the 116 (97.4%) MCTs showed a low-risk TIC (p < 0.0001). The area under the curve of the ROC analysis using the high-/intermediate-risk TIC on DCE MRI was the highest (0.99) for differentiating TSMs from MCTs: sensitivity 100%, specificity 97.4%, positive predictive value 75.0%, negative predictive value 100%, and accuracy, 97.6%. CONCLUSION: Compared to ovarian MCTs, ovarian TSMs are larger and have larger solid components with high- or intermediate-risk TICs on DCE MRI. Ovarian MCTs frequently show small solid components with fat tissue, ring-like enhancement, and a low-risk TIC on DCE MRI.

Tumor cell enrichment by tissue suspension improves sensitivity to copy number variation in diffuse gastric cancer with low tumor content.

The detection of copy number variations (CNVs) and somatic mutations in cancer is important for the selection of specific drugs for patients with cancer. In cancers with sporadic tumor cells, low tumor content prevents the accurate detection of somatic alterations using targeted sequencing. To efficiently identify CNVs, we performed tumor cell enrichment using tissue suspensions of formalin-fixed paraffin-embedded (FFPE) tissue sections with low tumor cell content. Tumor-enriched and residual fractions were separated from FFPE tissue suspensions of intestinal and diffuse-type gastric cancers containing sporadic tumor cells, and targeted sequencing was performed on 225 cancer-related genes. Sequencing of a targeted panel of cancer-related genes using tumor-enriched fractions increased the number of detectable CNVs and the copy number of amplified genes. Furthermore, CNV analysis using the normal cell-enriched residual fraction as a reference for CNV scoring allowed targeted sequencing to detect CNV characteristics of diffuse-type gastric cancer with low tumor content. Our approach improves the CNV detection rate in targeted sequencing with tumor enrichment and the accuracy of CNV detection in archival samples without paired blood.

Visualization of strain distribution in rubber bulk during friction.

This study employed a digital image correlation method (DICM) to experimentally quantify horizontal strain distribution in silicone rubber bulk during horizontal displacement against a stainless-steel sphere with/without glycerol. The strain distribution at different depth levels was measured by capturing the position of white powders in transparent rubber bulk. The experimental results indicated that each point in the rubber bulk moved while describing a horizontal loop during horizontal displacement depending on the position and lubrication conditions. This caused changes in the horizontal strain during horizontal displacement. These results suggest that the hysteresis term could be caused by changes in the vertical and horizontal strains.

Molecular features and prognostic factors of locally advanced microsatellite instability-high gastric cancer.

BACKGROUND: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer. METHODS: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer. RESULTS: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group. CONCLUSIONS: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors.

Successful correction of the transverse vaginal septum with a pinhole vaginal foramen using Y-V plasty: A case report.

The transverse vaginal septum, a rare Müllerian duct anomaly, presents diagnostic and therapeutic challenges owing to its variable location, thickness, and potential association with uterine malformations. Therefore, an accurate diagnosis and selection of an appropriate treatment are important. Herein, the case of a 28-year-old nonpregnant woman with sexual dysfunction attributable to a transverse vaginal septum is presented. The septum, approximately 5 mm thick, was situated low on the vaginal wall near the urethral opening, with a small central aperture. Employing Y-V plasty, full extension of the posterior and lateral vaginal walls was achieved while minimizing the manipulation of the anterior wall to avoid urethral injury. Postoperatively, the patient achieved sexual function without vaginal stenosis. Y-V plasty is a minimally invasive and effective approach for preventing postoperative stenosis in the treatment of a thin transverse vaginal septum located low on the vaginal wall.

Clinical Significance of Serum SCC Levels Before Treatment for Locally Advanced Cervical Squamous Cell Carcinoma.

BACKGROUND/AIM: Although serum squamous cell carcinoma (SCC) antigen values are known to be useful in predicting the prognosis of cervical SCC, they have only been examined in a cursory manner. This study aimed to meticulously investigate the clinical significance of serum SCC antigen levels in patients with locally advanced cervical squamous cell carcinoma (LACSC). PATIENTS AND METHODS: The study included patients who were diagnosed with local stage (T-stage) 1b3/2/3 LACSC and underwent initial treatment at our institute between January 2006 and December 2016 (T-1b3: n=30; T-2: n=75; T-3: n=34). The patients were divided into three groups based on pre-treatment SCC values, and differences in clinical background, laboratory and pathology findings, and prognosis were examined. RESULTS: No significant difference in the SCC distribution was observed among the T-1b3/2/3 cases with elevated SCC levels. In stages T-1b3, T-2, and T-3, most recurrences in the SCC-High group were distant (T-1b3: three out of five recurrences; T-2: six out of seven recurrences; T-3: four out of eight recurrences), while most recurrences in the SCC-Low group were pelvic (T-1b3: two out of three recurrences; T-2: eight out of eight recurrences; T-3: three out of three recurrences). CONCLUSION: In LACSC, serum SCC antigen levels before treatment correlate strongly with the recurrence site. Patients with low levels should be closely monitored for local recurrence, whereas those with high levels warrant vigilance for distant recurrence.

Genetic and Immunological Characterization of Brain Metastases from Solid Cancers.

BACKGROUND/AIM: Brain metastasis, a leading cause of cancer death, is a clinical challenge. Recently, genetic characterization of brain metastatic lesions based on next generation sequencing-based advanced technologies, such as single-cell RNA sequencing, has been performed to develop novel efficient therapies. The present study aimed to investigate brain-metastasis-specific biomarkers as well as relevant prognostic factors. PATIENTS AND METHODS: The genetic profiles and expression levels of immune response-associated genes and 820 cancer-associated genes were compared between primary cancer lesions and metastatic cancer lesions obtained from nine cancer patients at the Shizuoka Cancer Center. Cytokine and chemokine marker genes were analyzed via quantitative PCR. T-cell receptor (TCR) repertoire profiling was performed for the same patients. For survival analysis, survival data of 52 cancer patients with brain metastases were utilized. RESULTS: Comparison of driver mutation profiling between primary and metastatic lesions revealed shared core mutations in both lesions and a few new mutations in metastatic lesions. A high tumor mutation burden (TMB) was detected in metastatic lesions. Volcano plot analysis revealed specific features of the metastatic tumor microenvironment, such as cancer signaling promotion and immune suppression due to decreased immune cell infiltration. Survival analysis revealed that three genes, the TREML2 gene, the BTLA gene on activated microglia and the CERS2 gene on metastatic tumor, were potent prognostic factors. CONCLUSION: High TMB in metastatic lesions indicates potential benefit from immune checkpoint inhibitor usage for brain metastasis and TREML2 and BTLA are factors associated with poor prognosis. Activated microglia may be novel targets for the treatment of brain metastasis.

Investigation of imaging features in contrast-enhanced magnetic resonance imaging of benign and malignant breast lesions.

PURPOSE: This study aimed to enhance the diagnostic accuracy of contrast-enhanced breast magnetic resonance imaging (MRI) using gadobutrol for differentiating benign breast lesions from malignant ones. Moreover, this study sought to address the limitations of current imaging techniques and criteria based on the Breast Imaging Reporting and Data System (BI-RADS). MATERIALS AND METHODS: In a multicenter retrospective study conducted in Japan, 200 women were included, comprising 100 with benign lesions and 100 with malignant lesions, all classified under BI-RADS categories 3 and 4. The MRI protocol included 3D fast gradient echo T1- weighted images with fat suppression, with gadobutrol as the contrast agent. The analysis involved evaluating patient and lesion characteristics, including age, size, location, fibroglandular tissue, background parenchymal enhancement (BPE), signal intensity, and the findings of mass and non-mass enhancement. In this study, univariate and multivariate logistic regression analyses were performed, along with decision tree analysis, to identify significant predictors for the classification of lesions. RESULTS: Differences in lesion characteristics were identified, which may influence malignancy risk. The multivariate logistic regression model revealed age, lesion location, shape, and signal intensity as significant predictors of malignancy. Decision tree analysis identified additional diagnostic factors, including lesion margin and BPE level. The decision tree models demonstrated high diagnostic accuracy, with the logistic regression model showing an area under the curve of 0.925 for masses and 0.829 for non-mass enhancements. CONCLUSION: This study underscores the importance of integrating patient age, lesion location, and BPE level into the BI-RADS criteria to improve the differentiation between benign and malignant breast lesions. This approach could minimize unnecessary biopsies and enhance clinical decision-making in breast cancer diagnostics, highlighting the effectiveness of gadobutrol in breast MRI evaluations.

A Deep Learning-Based Assessment Pipeline for Intraepithelial and Stromal Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Carcinoma.

Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in patients with epithelial ovarian cancer. However, TIL evaluation has not been used in routine clinical practice because of reproducibility issues. The current study developed two convolutional neural network models to detect TILs and to determine their spatial location in whole slide images, and established a spatial assessment pipeline to objectively quantify intraepithelial and stromal TILs in patients with high-grade serous ovarian carcinoma. The predictions of the established models showed a significant positive correlation with the number of CD8+ T cells and immune gene expressions. Patients with a higher density of intraepithelial TILs had a significantly prolonged overall survival and progression-free survival in multiple cohorts. On the basis of the density of intraepithelial and stromal TILs, patients were classified into three immunophenotypes: immune inflamed, excluded, and desert. The immune-desert subgroup showed the worst prognosis. Gene expression analysis showed that the immune-desert subgroup had lower immune cytolytic activity and T-cell-inflamed gene-expression profile scores, whereas the immune-excluded subgroup had higher expression of interferon-γ and programmed death 1 receptor signaling pathway. The established evaluation method provided detailed and comprehensive quantification of intraepithelial and stromal TILs throughout hematoxylin and eosin-stained slides. It has potential for clinical application for personalized treatment of patients with ovarian cancer.

Clinical significance of initial symptoms in endometriosis-associated ovarian cancer.

Objective: Endometriosis is associated with various symptoms, but their severity varies from case to case. In this study, we investigated the reality of symptoms presented by patients with clinically early-stage endometriosis-associated ovarian cancer (EAOC) and explored the relationship between symptoms and laboratory/imaging findings, pathological findings, and prognosis. Materials and Methods: This was a retrospective case-control study of patients who received initial surgical treatment and were diagnosed with clinically early-stage EAOC, including ovarian endometrioid carcinoma (OEC), ovarian clear cell carcinoma (OCCC), and seromucinous borderline tumor (SMBT). Patients with OEC/OCCC diagnosed between 2006 and 2016 and those with SMBT diagnosed between 2006 and 2020 were included. Chi-square and Kaplan-Meier estimates were used for statistical analyses. Results: One hundred-seven patients (OEC, n=31; OCCC, n=39; SMBT, n=37) were included. Fifty-nine (55.1%) patients presented with symptoms, and the proportion of patients with OEC who presented with symptoms was significantly higher than that of others (OEC, 77.4%; OCCC, 43.6%; SMBT, 48.6%). The details of symptoms differed significantly among the pathological types (lower abdominal pain/abdominal discomfort/abnormal bleeding, OEC: 11/8/9; OCCC: 6/12/1; SMBT: 15/5/3). Only in the OEC group did symptomatic patients show significantly higher white blood cell (WBC) count and neutrophil/lymphocyte (N/L) ratio (symptomatic vs. asymptomatic, median: WBC count: 7250 vs. 5000, p=0.008; N/L ratio: 4.6 vs. 1.7, p=0.013). None of the asymptomatic patients showed recurrence during follow-up. Conclusion: Patients with EAOC show varying symptoms depending on the histological type of the tumor. Laboratory findings underlying symptoms also vary by histopathological type, which may reflect differences in the carcinogenesis process.

Neuroendocrine carcinoma of the uterine cervix with extensive pagetoid spread pattern.

There have been no reported cases of neuroendocrine carcinoma (NEC) of the cervix with pagetoid spread (Pag-S). A 44-year-old woman came to our department because of abnormal cytology that persisted immediately after a radical hysterectomy for NEC of the cervix. A mapping biopsy in a large area from the vaginal wall to the vulva revealed that synaptophysin/Ki-67-positive tumor cells were scattered within the epithelium in multiple areas, suggesting a wide Pag-S of NEC. Because tumor cells were found beyond the vaginal wall, the anterior pelvic exenteration was performed. Since we could pathologically confirm the complete resection and no distant metastases were detected, no adjuvant therapy was performed. Four years have passed since the initial treatment without any tumor recurrence. It is known that the prognosis of NEC of the cervix that invades beyond the cervix is poor; however, if there is a Pag-S pattern, a radical surgical treatment can be considered.

A case of bleeding shock induced by injury of the intercostal artery following percutaneous nephrolithotripsy.

Introduction: The risk of postoperative bleeding complications should be concerned to perform percutaneous nephrolithotripsy. Most of the vascular injuries occurred at the peripheral renal artery in the previous reports. We experienced a case of bleeding shock induced by the injury of the intercostal artery in the abdominal wall following percutaneous nephrolithotripsy. Case presentation: A 56-year-old woman had been in the bleeding shock status on the 2nd day after percutaneous nephrolithotoripsy. Emergently, contrast-enhanced computed tomography was performed and extravasation of contrast agents was seen in the abdominal wall. Injuries of the intercostal artery were identified in the angiography and controlled by transcatheter arterial embolization. Conclusion: The intercostal arteries could be injured in the anterolateral zone of the abdominal wall over the end of the ribs. Contrast-enhanced computed tomography was useful to detect the bleeding point. Transcatheter arterial embolization was an effective and safe method to control bleedings from them.

The Japanese breast cancer society clinical practice guidelines for breast cancer screening and diagnosis, 2022 edition.

This article provides updates to readers based on the newly published Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer Screening and Diagnosis, 2022 Edition. These guidelines incorporate the latest evaluation of evidence from studies of diagnostic accuracy. For each clinical question, outcomes for benefits and harms were established, and qualitative or quantitative systematic reviews were conducted. Recommendations were determined through voting by a multidisciplinary group, and guidelines were documented to facilitate shared decision-making among patients and medical professionals. The guidelines address screening, surveillance, and pre- and postoperative diagnosis of breast cancer. In an environment that demands an integrated approach, decisions are needed on how to utilize modalities, such as mammography, ultrasound, MRI, and PET/CT. Additionally, it is vital to understand the appropriate use of new technologies, such as tomosynthesis, elastography, and contrast-enhanced ultrasound, and to consider how best to adapt these methods for individual patients.

Risk factors for lateral lymph node metastasis based on the molecular profiling of rectal cancer.

AIM: The association between molecular profiles and lateral lymph node metastasis (LLNM) in patients with rectal cancer remains unclear. Therefore, this study aimed to identify the molecular profiles of rectal cancer associated with LLNM. METHOD: We retrospectively examined patients who underwent rectal cancer surgery with lateral lymph node dissection without preoperative treatment and whose surgically resected specimens were evaluated using multiomics-based analyses from 2014 to 2019. We compared the clinical characteristics and molecular profiles of patients with pathological LLNM (pLLNM+) with those of patients without (pLLNM-) and identified risk factors for LLNM. RESULTS: We evaluated a total of 123 patients: 18 with and 105 without pLLNM. The accumulation of mutations in genes key for the development of colorectal cancer were similar between the groups, as was the tumour mutation burden. The distribution of consensus molecular subtypes (CMS) was significantly different between the groups (p = 0.0497). The pLLNM+ patients had a higher prevalance of CMS4 than the pLLNM- patients (77.8% vs. 51.4%). According to the multivariate analysis, the independent risk factors for LLNM were a short-axis diameter of the lateral lymph node of ≥6.0 mm and CMS4; furthermore, the presence of either or both had a sensitivity of 100% for the diagnosis of LLNM. CONCLUSION: Lateral lymph node size and CMS4 are useful predictors of LLNM. The combination of CMS classification and size criteria was remarkably sensitive for the diagnosis of LLNM.

Impact of Mutations in Subunit Genes of the Mammalian SWI/SNF Complex on Immunological Tumor Microenvironment.

BACKGROUND/AIM: Recently, inactivating somatic mutations of SWI/SNF chromatin-remodeling genes in cancers have been reported. However, few studies have been performed regarding the immunological analysis of the tumor microenvironment (TME) in chromatin remodeling complex gene-mutated tumors. In the present study, we identified cancer patients harboring various mammalian SWI/SNF complex mutations and investigated the immunological features in those mutated cancers. PATIENTS AND METHODS: Cancer patients harboring any type of chromatin remodeling complex gene mutation were selected and clinicopathological features were compared between chromatin remodeling complex gene expression-low and expression-high groups. Specifically, expression levels of immune response-associated genes and cancer-associated genes were compared between the SMARCA4 expression-low and expression-high groups using volcano plot analysis. RESULTS: Among cancers harboring PBRM1, SAMRACA4 and ARID2 gene mutations, T-cell marker and mature B-cell marker genes were up-regulated in the tumor. Specifically, T-cell effector genes (CD8B, CD40LG), central memory marker genes (CD27, CCR7) and mature B-cell marker genes (CD20, CD38, CD79 and IRF4) were up-regulated, and cancer-associated genes including MYB, MYC and AURKB genes were down-regulated in the SMARCA4 expression-low group. Remarkably, heatmap of gene expression and immunohistochemistry (IHC) data demonstrated that the tertiary lymphoid structure (TLS) gene signature of mature B cells was up-regulated in SMACA4 gene-mutated stomach cancers. CONCLUSION: These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal down-regulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors.