Diagnostic accuracy of preoperative quantitative susceptibility mapping for detecting histologic intraplaque hemorrhage in cervical ICA stenosis in patients undergoing carotid endarterectomy.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping (QSM) has been proposed to assess intraplaque hemorrhage (IPH) in the carotid artery. The purpose of this study was to compare the diagnostic accuracy of preoperative QSM with that of the conventional T1-weighed (T1W) three-dimensional (3D)-FSE sequence for detecting IPH in cervical ICA stenosis in patients undergoing carotid endarterectomy (CEA) using histology as the reference standard. MATERIALS AND METHODS: Carotid T1W 3D-FSE and QSM images were obtained from 16 patients with cervical ICA stenosis before CEA. Relative signal intensity (RSI) and susceptibility of the ICA were measured on three axial images including the location of most severe stenosis on T1W 3D-FSE and QSM images, respectively. Three transverse sections of carotid plaques excised by CEA, which corresponded with images on MRI, were stained with H&E, antibody against glycophorin A and Prussian blue, and the relative area (RA) of histologic IPH was calculated. RESULTS: The correlation coefficient was significantly greater between susceptibility and RA-histologic IPH (ρ = 0.691) than between RSI and RA-histologic IPH (ρ = 0.413; P = .0259). The areas under the receiver operating characteristic curves for detecting histologic sections consisting primarily of IPH (RA-histologic IPH > 40.7%) tended to be greater for susceptibility (0.964) than for T1WI FSE-RSI (0.811). Marginal homogeneity was observed between susceptibility and histologic sections consisting primarily of IPH (P = .0412) but not between T1W FSE-RSI and histologic sections consisting primarily of IPH (P = .1824). CONCLUSIONS: Pre-CEA QSM detects histologic IPH in cervical ICA stenosis more accurately than preoperative T1W 3D-FSE imaging. ABBREVIATIONS: QSM = quantitative susceptibility mapping; IPH = intraplaque hemorrhage; T1W = T1-weighed; 3D = three-dimensional; CEA = carotid endarterectomy; RSI = relative signal intensity; RA = relative area.

Gastric cancer after laparoscopic adjustable gastric banding: A case report.

INTRODUCTION: Gastric cancer occurring after bariatric and metabolic surgeries is rare. We report a case of gastric cancer that developed at 14 years after laparoscopic adjustable gastric banding. PRESENTATION OF CASE: The patient was an obese 81-year-old woman who underwent LAGB at 14 years prior when her body mass index was 35.3 kg/m2. Anemia was noted during a visit to her family clinic. Subsequent esophagogastroduodenoscopy revealed a type 5 lesion (Macroscopic Classification of the Gastric Cancer in Japanese Classification of Gastric Carcinoma, The 15th Edition) near the greater curvature of the posterior wall of the gastric antrum. A biopsy indicated a poorly differentiated adenocarcinoma. Computed tomography showed no evidence of invasion of other organs, lymph node metastasis, or distant metastasis. The patient underwent laparoscopy-assisted distal gastrectomy, banding removal, Roux-en-Y reconstruction. The histopathological diagnosis was pT3N2M0 and pStage IIIA. The patient exhibited an uneventful postoperative course and was discharged on postoperative day 8. The patient has remained recurrence-free up to 12 months postoperatively. DISCUSSION: While metabolic surgeries have been shown to reduce the risk of developing malignant diseases, including gastric cancer, the present patient developed gastric cancer at 14 years after laparoscopic adjustable gastric banding. The patient developed gastric cancer during a long-term course, indicating the importance of periodic examinations after metabolic surgery. CONCLUSIONS: Previous studies showed metabolic surgeries for obesity reduce the risk of developing malignancies, including gastric cancer; however, the present case suggests that gastric cancer may develop over a long-term course.

A gastric invasive tubular adenocarcinomatous lesion arising from foveolar-type neoplasia: molecular histogenesis.

Here, we report a rare case of a depressed lesion exhibiting both tubular differentiated adenocarcinomatous (TDA) and intraepithelial foveolar neoplasia (IFN) components (with the histological appearance of foveolar hyperplasia due to low-grade atypia). Histologically, the TDA surrounded the IFN, suggesting that the TDA may have originated from the IFN. Therefore, we examined molecular alterations in the TDA and IFN components separately. MUC5AC and MUC6 expression was observed immunohistochemically in both components. p53 expression was wild type in both components, suggesting no mutation of TP53. We investigated allelic imbalances at multiple loci (1p, 3p, 4p, 5q, 8q, 9p, 13q, TP53, 18q, and 22q), mutations (KRAS, BRAF, and GNAS), and DNA methylation and microsatellite status in both components using PCR-based analyses. Although multiple allelic imbalances were common to both components, allelic imbalances at 3p and TP53 were found only in the TDA component. No mutations were found, and DNA methylation status was low epigenotype for both components. Ultimately, this tumor was considered microsatellite stable. Considering the origin of TDA, which is frequently encountered in routine practice, IFN may develop into TDA.

A genome-wide study of gastric intramucosal neoplasia based on somatic copy number alterations, gene mutations, and mRNA expression patterns.

We performed comprehensive analyses of somatic copy number alterations (SCNAs) and gene expression profiles of gastric intramucosal neoplasia (IMN) using array-based methods in 97 intestinal-type IMNs, including 39 low-grade dysplasias (LGDs), 37 high-grade dysplasias (HGDs), and 26 intramucosal carcinomas (IMCs) with stromal invasion of the lamina propria to identify the molecular mechanism of IMN. In addition, we examined gene mutations using gene panel analyses. We used cluster analyses for exclusion of arbitrariness to identify SCNA patterns and expression profiles. IMNs were classified into two distinct subgroups (subgroups 1 and 2) based on SCNA patterns. Subgroup 1 showed a genomic stable pattern due to the low frequency of SCNAs, whereas subgroup 2 exhibited a chromosomal instability pattern due to the high frequencies of SCNAs and TP53 mutations. Interestingly, although the frequencies of LGD and HGD were significantly higher in subgroup 1 than in subgroup 2, IMC was commonly found in both types. Although the expression profiles of specific mRNAs could be used to categorise subgroups 1 and 2, no clinicopathological findings correlated with either subgroup. We examined signalling pathways specific to subgroups 1 and 2 to identify the association of each subgroup with signalling pathways based on gene ontology tree visualisation: subgroups 1 and 2 were associated with haem metabolism and chromosomal instability, respectively. These findings reveal a comprehensive genomic landscape that highlights the molecular complexity of IMNs and provide a road map to facilitate our understanding of gastric IMNs.

The pattern-based interpretation of p53 immunohistochemical expression as a surrogate marker for TP53 mutations in colorectal cancer.

Mutations in the TP53 gene, most commonly observed in colorectal cancer (CRC), play an essential role in colorectal carcinogenesis. Although p53 immunohistochemical (IHC) expression patterns have been argued to serve as an excellent surrogate marker for TP53 mutations, its performance has not been confirmed in CRC. We aimed to determine whether p53 IHC expression patterns accurately predict TP53 mutation status as examined by next-generation sequencing (NGS). We performed p53 IHC and sequencing of TP53 by NGS in 92 CRC cases with a microsatellite stable phenotype to investigate the correlation between TP53 mutation status and p53 IHC expression. The concordance between p53 IHC and TP53 mutation was 84/92 (91.3%) overall. However, 6 mutant cases were found in 39 cases with a wild-type IHC pattern. Additionally, there were two discordant cases in which an abnormal p53 IHC pattern (overexpression or cytoplasmic pattern) was found, while NGS detected wild-type p53. Therefore, the optimized p53 IHC performs well and serves as a surrogate test for TP53 mutation in CRC cases. Furthermore, it demonstrates excellent reproducibility between two independent experienced pathologists and may have novel clinical utility for molecular classification algorithms in CRC. We suggest that the four-tier classification of p53 IHC patterns is helpful to evaluate molecular colorectal carcinogenesis.

The clinicopathological impact of tumor-associated macrophages in patients with cutaneous malignant melanoma.

BACKGROUND: Tumor-associated macrophages (TAMs) are an immune component of the cutaneous malignant melanoma (CMM) microenvironment and affect tumor growth. TAMs can polarize into different phenotypes, that is, proinflammatory M1 and anti-inflammatory M2 macrophages. However, the role of the macrophage phenotype in CMM remains unclear. METHODS: We examined 88 patients with CMM. Tissue microarrays were constructed, and the density of M1 and M2 macrophages was analyzed by immunohistochemistry. Immune cells coexpressing CD68 and phosphorylated signal transducer and activator of transcription 1 (pSTAT1) were considered M1 macrophages, whereas those coexpressing CD68 and c-macrophage activating factor (c-Maf) were defined as M2 macrophages. These TAMs were counted, and the relationships between the density of M1 and M2 macrophages and clinicopathological factors including prognosis were investigated. RESULTS: The CD68/c-Maf score ranged from 0 to 34 (median: 5.5). The patients were divided based on the median score into the CD68/c-Maf high (≥5.5) and low (<5.5) expression groups. Univariate and multivariate analyses revealed that CD68/c-Maf expression was an independent predictive factor for progression-free survival and an independent prognostic factor for overall survival. CD68/pSTAT1 expression was found in only two patients. CONCLUSION: We suggest that CD68/pSTAT1 coexpression is rarely observed in patients with CMM, and high CD68/c-Maf expression is a predictor of worse prognosis in these patients.

Microbiome mediating methane and nitrogen transformations in a subterranean estuary.

Subterranean estuaries (STEs) are important coastal biogeochemical reactors facilitating unique niches for microbial communities. A common approach in determining STE greenhouse gas and nutrient fluxes is to use terrestrial endmembers, not accounting for microbially mediated transformations throughout the STE. As such, the microbial ecology and spatial distribution of specialists that cycle compounds in STEs remain largely underexplored. In this study, we applied 16S rRNA amplicon sequencing with paired biogeochemical characterisations to spatially evaluate microbial communities transforming greenhouse gases and nutrients in an STE. We show that methanogens are most prevalent at the terrestrial end (up to 2.81% relative abundance) concomitant to the highest porewater methane, carbon dioxide and dissolved organic carbon concentrations (0.41 ± 0.02 µM, 273.31 ± 6.05 µM and 0.51 ± 0.02 mM, respectively). Lower ammonium concentrations corresponded with abundant nitrifying and ammonia-oxidising prokaryotes in the mixing zone (up to 11.65% relative abundance). Methane, ammonium and dissolved organic carbon concentrations all decreased by >50% from the terrestrial to the oceanic end of the 15 m transect. This study highlights the STE's hidden microbiome zonation, as well as the importance of accounting for microbial transformations mitigating nutrient and greenhouse gas fluxes to the coastal ecosystems.

Prognostic and predictive value of CD163 expression and the CD163/CD68 expression ratio for response to adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinoma.

BACKGROUND: Macrophages infiltrating the tumor microenvironment are defined as tumor-associated macrophages (TAMs). TAMs can be polarized into different phenotypes, that is, proinflammatory M1 macrophages or anti-inflammatory M2 macrophages. Particularly, M2 macrophages promote angiogenesis, wound healing, and tumor growth. This study aimed to evaluate whether M2 TAMs can serve as a useful marker to predict prognosis and benefit from adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinomas (SCCs). METHODS: We examined 104 patients with SCC. Tissue microarrays were constructed, and the density of TAMs was analyzed by immunohistochemistry for expression of CD68 and CD163. The relationship between CD68 and CD163 expression and the CD163/CD68 expression rate and clinicopathological characteristics including patient outcomes were investigated. In addition, propensity score matching (PSM) analysis was conducted to test the hypothesis that these cells significantly influenced chemotherapy responses. RESULTS: Univariate analysis revealed that pathological stage, CD163 expression, and the CD163/CD68 expression ratio were significant prognostic factors. Multivariate analysis showed that these factors were all independent prognostic factors. Thirty-four pairs were determined by using PSM analysis. Patients with a low CD163/CD68 expression ratio benefited more from adjuvant chemotherapy than those with a high ratio. CONCLUSION: We suggest that M2 TAMs may be a useful marker to predict prognosis and differential benefit from adjuvant chemotherapy in patients with surgically resected lung SCCs.

Rectal Carcinoma With a Sarcomatoid Component: A Case Report With Detailed Immunohistochemistry, Molecular Analysis, and Literature Review.

Introduction. Carcinoma with sarcomatoid components is a highly malignant tumor exhibiting both epithelial and stromal malignant differentiation. Its tumorigenesis is associated with epithelial-mesenchymal transition (EMT), and phenotypic changes from carcinoma to sarcoma are associated with TP53 mutations. Case presentation. A 73-year-old female with bloody stool was diagnosed with rectal adenocarcinoma. She underwent trans-anal mucosal resection. Histopathologically, the tumor cells showed 2 morphologically distinct populations. One was composed of well-formed to fused glands or cribriform glands and was considered a moderately differentiated adenocarcinoma. The other consisted of pleomorphic discohesive atypical tumor cells with spindle and/or giant cell features, which was considered a sarcomatous tumor. Immunohistochemistry analysis showed that E-cadherin expression changed from positive to negative in the sarcomatous component. On the other hand, ZEB1 and SLUG were positive. Finally, she was diagnosed with carcinoma with a sarcomatoid component. We performed a mutation analysis by next genome sequencing and found KRAS and TP53 mutations in both carcinomatous and sarcomatous components. Conclusions. Immunohistochemistry and mutation analyses revealed tumorigenesis of rectal carcinoma with sarcomatoid components correlated with EMT and TP53 mutations.

Gastroblastoma mimics the embryonic mesenchyme of the foregut: a case report.

BACKGROUND: Gastroblastoma is a rare gastric tumor composed of epithelial and spindle cell components. The characteristic MALAT-GLI1 fusion gene has only been identified in 5 reported cases. We report the morphological characterization of gastroblastoma with the MALAT1-GLI1 fusion gene in a young Japanese woman. CASE PRESENTATION: A 29-year-old Japanese woman visited Iwate Medical University Hospital with upper abdominal pain. Computed tomography revealed a tumor in expansive lesions involving the gastric antrum. Histologically, we observed a biphasic morphology composed of epithelial and spindle cell components. The epithelial components appeared as slit-like glandular structures with tubular or rosette-like differentiation. The spindle cell components consisted of short spindle-shaped oval cells. Immunohistochemical (IHC) analysis revealed that the spindle cell component was positive for vimentin, CD10, CD56, GLI1, and HDAC2, and focally positive for PD-L1. The epithelial component was positive for CK AE1/AE3, CAM5.2, and CK7, and negative for CK20 and EMA. Both components were negative for KIT, CD34, DOG1, SMA, desmin, S100 protein, chromogranin A, synaptophysin, CDX2, and SS18-SSX. The MALAT-GLI1 fusion gene was detected molecularly. CONCLUSIONS: We report the following new findings with this case: (i) gastric tumors mimic the gastrointestinal mesenchyme in the embryonic period; (ii) nuclear expression of PD-L1 and HDAC2 were observed in the spindle cell component of a gastroblastoma. We speculate that histone deacetylase (HDAC) inhibitors may offer a promising treatment option for gastroblastoma.

Comprehensive Analysis of microRNA Expression During the Progression of Colorectal Tumors.

BACKGROUND: No effective early diagnostic biomarkers are available for colorectal cancer (CRC). Therefore, we sought to identify new biomarkers that could identify CRC from progression as a pre-cancerous lesion to its invasive form. Recent studies have shown that microRNAs (miRs) are associated with the onset of cancer invasion and progression. AIMS: We hypothesized that the identification of miRs associated with CRC might be useful to detect this disease at early stages. METHODS: We conducted an integrated analysis of 79 isolated colorectal tumor glands, including adenomas, intramucosal cancers, and invasive CRCs that showed a microsatellite stable phenotype using GeneChip miRNA 4.0 microarray assays. The colorectal tumors we examined were divided into 2 cohorts (42 in the first cohort and 37 in the second cohort). RESULTS: First, cluster analysis was performed to stratify expression patterns of multiple miRs that were pooled according to the following criteria: fold change in expression (< -2.0 or > 2.0), p < 0.05, and mature miRs. As a result, the expression patterns of pooled miRs were subdivided into 3 subgroups that were correlated with tumor grade. Each subgroup was characterized by specific miRs. In addition, we found that specific miRs, including miR-140-3p and miR-378i, were closely associated with cancer invasion. Finally, we analyzed paired dysregulated miRs between adenomatous and cancerous components present within the same tumor. DISCUSSION: We showed that several miRs were dysregulated during progression from adenoma to intramucosal cancer. Specific miRs may have key roles in progression from intramucosal tumor to invasive CRC.

Differential Expression in the Tumor Microenvironment of mRNAs Closely Associated with Colorectal Cancer Metastasis.

BACKGROUND: Metastasis of colorectal cancer (CRC) is a major cause of CRC-related mortality. However, the detailed molecular mechanism of CRC metastasis remains unknown. A recent study showed that the tumor microenvironment, which includes cancer cells and the surrounding stromal cells, plays a major role in tumor invasion and metastasis. Identification of altered messenger RNA (mRNA) expression in the tumor microenvironment is essential to elucidation of the mechanisms responsible for tumor progression. This study investigated the mRNA expression of genes closely associated with metastatic CRC compared with non-metastatic CRC. METHODS: The samples examined were divided into cancer tissue and isolated cancer stromal tissue. The study examined altered mRNA expression in the cancer tissues using The Cancer Genome Atlas (TCGA) (377cases) and in 17 stromal tissues obtained from our laboratory via stromal isolation using an array-based analysis. In addition, 259 patients with CRC were enrolled to identify the association of the candidate markers identified with the prognosis of patients with stage 2 or 3 CRC. The study examined the enriched pathways identified by gene set enrichment analysis (GSEA) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) module in both the TCGA dataset and isolated stromal tissue. RESULTS: As a result, whereas tenascin-C, secreted phosphoprotein 1 and laminin were expressed in metastatic CRC cells, olfactory receptors (ORs) 11H1 and OR11H4 were expressed in stromal tissue cells isolated from metastatic CRC cases. Finally, upregulated expression of tenascin-C and OR11H4 was correlated with the outcome for CRC patients. CONCLUSION: The authors suggest that upregulated expression levels of tenascin-C and OR11H1 play an important role in CRC progression.

The new IASLC grading system for invasive non-mucinous lung adenocarcinoma is a more useful indicator of patient survival compared with previous grading systems.

BACKGROUND: The International Association for the Study of Lung Cancer (IASLC) Pathology Committee recently proposed a new histological grading system for invasive lung adenocarcinoma (ADC). This study evaluated the usefulness of this grading system. METHODS: A total of 395 patients with ADC were examined. ADCs were reclassified based on comprehensive histological subtyping according to the IASLC grading system. We evaluated the following histological grading systems for invasive ADC: the architectural (Arch), Sica's grading, and IASLC grading systems. Multivariate analyses of overall and recurrence-free survival (RFS) based on these three grading systems were performed using Cox proportional hazards models. RESULTS: Multivariate analysis showed that all three grading systems were useful for predicting the outcomes of patients at all stages. However, the IASLC grading system was superior to the Arch and Sica's grading systems in differentiating grade 3 from grade 1 ADCs in terms of both overall survivals (IASLC vs. Arch vs. Sica's grading systems: hazard ratio [HR] = 3.77 vs. 3.03 vs. 2.63) and RFS (HR = 4.25 vs. 2.69 vs. 2.4). CONCLUSION: The newly proposed IASLC grading system was useful for predicting patient outcomes and was superior to the other grading systems in detecting high-grade malignancy.

An autopsy case of hyperimmunoglobulin E syndrome with coronary fibrinoid necrotizing arteritis and an aneurysm.

We report a case of hyperimmunoglobulin (Ig) E syndrome (HIES) with a coronary artery aneurysm (CAA) in a 25-year-old Japanese man. He died suddenly due to chronic heart failure associated with HIES. We noted a CAA at the trunk of the left coronary artery and granulomatous and fibrinoid necrotizing arteritis of the middle portion of the left anterior descending during the autopsy. We speculate herein on the relationship between the aneurysm and arteritis. These findings facilitate a better understanding of the pathogenesis underlying HIES.

High expression of fibroblast-activating protein is a prognostic marker in non-small cell lung carcinoma.

BACKGROUND: Fibroblast-activating protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) in many human carcinomas and in some types of carcinoma cells. Here, we examined the proportion of FAP protein expression in non-small cell lung carcinoma (NSCLC) and investigated the correlation of FAP expression with clinicopathological background. METHODS: In total, 344 NSCLC tissues were examined. Tissue microarrays were constructed, and FAP expression was analyzed using immunohistochemistry. The status of FAP expression in tumor cells and CAFs was correlated with clinicopathological background, molecular features, and patient outcomes. RESULTS: A total of 280 patients (81.4%) had low FAP expression, and 64 patients (18.6%) had high FAP expression in tumor cells. In CAFs, 230 patients (66.9%) had low FAP expression, and 114 patients (33.1%) had high FAP expression. In multivariate analyses, high FAP expression in tumor cells was an independent predictive factor of both overall survival (OS; hazard ratio [HR] = 2.57, 95% confidence interval [CI]: 1.49-4.42, p < 0.001) and recurrence-free survival (RFS; HR = 2.13, 95% CI: 1.38-3.29, p < 0.001). Based on combinations of FAP expression in tumor cells and CAFs, patients with LowT /LowCAFs had better OS and RFS than did those in the other subgroups. By contrast, patients with HighT /HighCAFs had poor OS and RFS compared with those in the other subgroups. CONCLUSIONS: Overall, FAP expression in tumor cells and the combination FAP expression in tumor cells and CAFs were strongly associated with patient survival and may be useful predictive biomarkers for patient outcomes in NSCLC.

Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences.

Background: Although MicroRNAs (miRNAs) play important roles in various biological processes, the biological functions of miRNAs are achieved through mRNAs. The aim of this study is to identify dysregulated miRNA/mRNA expression patterns in colorectal tumors. Methods: We examined 42 colorectal tumors [15 adenomas, 8 intramucosal cancers (IMCs), and 19 invasive colorectal cancers (CRCs)] with the microsatellite stable (MSS) phenotype (first cohort). The first cohort was used for genome-wide miRNA and mRNA expression arrays, whereas the second cohort (37 colorectal neoplasias) was used for validation analyses. Finally, we used 15 cases of "adenoma in/with carcinoma" to identify network patterns of miRNAs/mRNAs that were directly associated with neoplastic progression. In addition, simple regression analysis for array-based and RT-PCR analyses was performed to select candidate miRNA-mRNA pairs. Transfection of miRNA mimics was also performed to confirm whether target mRNA expression is affected by specific miRNAs. Results: Specific paired miRNA/mRNA networks, including hsa-miR-34a-5p/SLC12A2, hsa-miR-15b-5p/SLC12A2, hsa-miR-195-5p/SLC12A2, hsa-miRNA-502-3p/OLFM4, hsa-miRNA-6807-5p/ZG16, and hsa-miRNA 3064-5p/SH3BGRL3, were identified in samples of adenoma, IMC, and CRC with the MSS phenotype. In adenomatous lesions obtained from the same tumor with a carcinomatous lesion, we identified pairs of miRNA-130a-3p/HSPA8 and miRNA-22-3p/RP53 that were linked to multiple pathways. On the other hand, 2 pairs of miRNA/mRNA (miRNA-660-5p and miRNA-664a-5p/APP) were found in isolated carcinomatous glands. Ectopic expression of miRNA 3064-5p suppressed SH3BGRL3 expression. Conclusions: We found that networks based on specific pairs of miRNAs/mRNAs contribute to progression from adenomatous and carcinomatous lesions. Our results provide insights into the molecular tumorigenesis of colorectal tumors.

Helicobacter pylori Modulated Host Immunity in Gastric Cancer Patients With S-1 Adjuvant Chemotherapy.

BACKGROUND: Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systemic mechanisms modulated by HP are involved in this more favorable outcome. METHODS: A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1) and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse-free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors. RESULTS: Among 491 patients that were analyzed, 175 (36%) and 316 (64%) patients were HP+ and HP-, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 dose (Pinteraction = .049) and PD-L1 (P = .02). HP+ patients in the PD-L1- group had statistically higher 5-year OS and RFS than HP- patients (81% vs 68%; P = .0011; hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.303 to 0.751, and 76% vs 63%; P = .001; HR = 0.508, 95% CI = 0.335 to 0.771, respectively). The 5-year OS and RFS was also statistically higher for HP+ compared with HP- patients in the "PD-L1- and S-1-r educed" group (86% vs 46%; P = .001; HR = 0.205, 95% CI = 0.07 to 0.602, and 83% vs 34%; P = .001; HR = 0.190, 95% CI = 0.072 to 0.498, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival. CONCLUSION: This retrospective study suggests that an HP-modulated host immune system may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.

Genome-wide analysis of mRNA and microRNA expression in colorectal cancer and adjacent normal mucosa.

mRNA expression varies in human cancers. Such altered mRNA expression is negatively regulated by the expression of microRNAs (miRNAs), which play an important role in human tumorigenesis. According to this theory, inverse mRNA/miRNA expression may be a direct driver of cancer development, and certain genetic events may occur prior to the development of any discernible histological abnormalities. We examined the inverse expression between mRNAs and their corresponding miRNAs in colorectal cancer (CRC) and adjacent normal mucosa and performed pathway analysis to identify mRNA/miRNA networks. The cancer samples were divided into first (20 cases) and second (24 cases) cohorts, and 48 samples were obtained from two sections of the normal mucosa adjacent to the tumors from the second cohort. We investigated mRNAs with commonly altered expression in CRC and adjacent normal mucosa using isolated cancer glands and normal crypts from the first cohort, compared with that of distal normal crypts, using an array-based method. As a result, significant inverse correlations between CEACAM1 and miRNA-7114-5p and between AK1 and miRNA-6780-5p were found in CRC and adjacent normal mucosa. We validated these correlations in the second cohort using RT-PCR. To confirm these findings, transfection and immunohistochemical assays were also performed, which verified the inverse correlation between CEACAM1 and miRNA-7114-5p. Our findings suggest that the inverse correlations between the CEACAM1/miRNA-7114-5p and possibly AK1/miRNA-6780-5p pairs play an important role in early CRC development, and may help identify potential molecular targets for early detection of CRC.