Elevated expression of Axin2 in intestinal metaplasia and gastric cancers.

BACKGROUND: The Wnt signaling pathway regulates crucial cellular processes, including stem cell development and tissue repair. Dysregulation of this pathway, particularly ß-catenin stabilization, is linked to colorectal carcinoma and other tumors. Axin2, a critical component in the pathway, plays a role in ß-catenin regulation. This study examines Axin2 expression in normal gastric mucosa and various gastric pathologies. METHODS: Formalin-fixed and paraffin-embedded tissue samples from normal stomach, gastritis, intestinal metaplasia (IM), and gastric carcinoma were collected. Axin2 and ß-catenin expression were evaluated using RNA in situ hybridization and immunohistochemistry, respectively. Histo-scores (H-scores) were calculated to quantify expression levels of Axin2. Associations between Axin2 expression and clinicopathological variables were examined. RESULTS: Axin2 expression was examined in normal stomach, gastritis, and IM tissues. Axin2 expression was mainly observed in the surface and isthmus areas in the normal stomach and gastritis, whereas Axin2 expression was markedly higher at the bases of IM. Axin2 H-scores were significantly elevated in IM (mean ± standard deviation [SD], 87.0 ± 38.9) compared to normal (mean ± SD, 18.0 ± 4.5) and gastritis tissues (mean ± SD, 33.0 ± 18.6). In total, 30% of gastric carcinomas showed higher Axin2 expression. Axin2 expression did not have significant associations with age, sex, Lauren classification, histological differentiation, invasion depth, and lymph node metastasis. However, a strong positive correlation was observed between Axin2 and nuclear ß-catenin in gastric carcinomas (p < .001). CONCLUSIONS: Axin2 expression was significantly increased in IM compared to normal and gastritis cases. In addition, Axin2 showed a strong positive association with nuclear ß-catenin expression in gastric carcinomas, demonstrating a close relationship with abnormal Wnt/ß-catenin signaling pathway.

The association between ephrin receptor-A1 expression and survival in patients with cancer: a meta-analysis.

Background: Ephrin receptor-A1 (EPHA1) participates in various developmental processes by engaging in cell adhesion, migration, and tissue boundary formation. EPHA1 is also associated with cancer progression and poor prognosis. However, the results of individual studies were inconsistent. Therefore, we aimed to systematically evaluate the association between survival and EPHA1 expression in patients with cancer. Methods: We searched electronic databases including PubMed, Embase, Scopus, and the Cochrane library until February 8, 2022. The pooled hazard ratio (HR) with 95% confidence interval (CI) was calculated to explore the relationship between EPHA1 expression and survival in patients with cancer. Funnel plots and Egger's regression tests were conducted to evaluate publication bias, and sensitivity analysis was performed to determine the reliability of the pooled results. Results: Eight studies with 1079 cancer patients were enrolled. EPHA1 expression was associated with progression-free survival (PFS) (HR 1.79, 95% CI: 1.49-2.15, P<0.001). EPHA1 expression was also associated with poor overall survival (HR 2.23, 95% CI: 1.42-3.51, P<0.001), higher tumor stage [odds ratio (OR) 1.74, 95% CI: 1.15-2.61, P=0.008], and lymph node metastasis (OR 1.88, 95% CI: 1.24-2.87, P=0.003) in patients with gastric cancer. Discussion: EPHA1 expression was significantly associated with PFS in patients with cancer.

Differential epithelial and stromal LGR5 expression in ovarian carcinogenesis.

Lgr5 has been identified as a marker of the stem/progenitor cells in the murine ovary and oviduct by lineage tracing. However, little is known regarding LGR5 expression or its functional significance in human ovary tissues. Here, using RNA in situ hybridization and/or immunohistochemistry, we thoroughly investigated LGR5 expression in normal human ovaries, fallopian tubes and various ovarian tumors. We discovered that LGR5 expression is negligible in the human ovary surface epithelium, whereas ovarian stromal cells normally express low levels of LGR5. Remarkably, fallopian tube epithelium, inclusion cysts and serous cystadenomas with a Müllerian phenotype expressed high levels of LGR5, and LGR5 expression was restricted to PAX8+/FOXJ1- secretory cells of the tubal epithelium. Strong stromal LGR5 expression without epithelial LGR5 expression was consistently observed in the path from serous cystadenoma to serous borderline tumor to low grade serous carcinoma (LGSC). Unlike LGSC, high grade serous carcinoma (HGSC), clear cell carcinoma, endometrioid carcinomas displayed various epithelial-stromal LGR5 expression. Notably, high levels of LGR5 expression were observed in serous tubal intraepithelial carcinoma, which slightly declined in invasive HGSC. LGR5 expression was significantly associated with improved progression-free survival in HGSC patients. Moreover, in vitro assays demonstrated that LGR5 expression suppressed tumor proliferation and migratory capabilities. Taken together, these findings indicate a tumor-suppressive role for LGR5 in the progression of HGSC.

Atypical Fibroxanthoma Resected without Auricular Deformity in an Elderly Patient: A Case Study.

Atypical fibroxanthoma (AFX) is a dermal spindle-cell cutaneous malignancy, which is a relatively benign type of skin cancer that occurs in the elderly with sun-damaged skin. This is a case study of a rapidly enlarged left auricular mass lesion in an elderly patient who was diagnosed with AFX based on histopathological and immunohistochemical findings, and then treated by complete excision to prevent recurrence or metastasis. There was no recurrence during the 1-year follow-up. For otolaryngologists or plastic surgeons, recognizing the clinical and pathologic characteristics of AFX is important for accurate diagnosis and treatment.

Increased CD9 expression predicts favorable prognosis in human cancers: a systematic review and meta-analysis.

BACKGROUND: CD9 is implicated in cancer progression and metastasis by its role in suppressing cancer cell proliferation and survival. However, the prognostic and clinicopathological significance of CD9 expression is controversial. Therefore, the current meta-analysis was conducted to determine the prognostic and clinicopathological significance of CD9 expression in cancer patients. METHODS: Eligible studies were selected through database search of PubMed, Embase and Cochrane library up to April 5 2020. The necessary data were extracted from the included studies. Pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the prognostic and clinicopathological significance of CD9 expression in cancer patients. RESULTS: A total of 17 studies consisting of 3456 cancer patients were included in this meta-analysis. An increased CD9 expression was significantly associated with a more favorable overall survival (OS) (HR 0.47, 95% CI 0.31-0.73, p = 0.001) and disease-free survival (DFS) (HR 0.48, 95% CI 0.30-0.79, p = 0.003). In subgroup analysis of cancer type, an increased CD9 expression was associated with increased OS in breast cancer and digestive system cancer, and with increased DFS in head and neck cancer and leukemia/lymphoma. Additionally, an increased CD9 expression significantly correlated with lower overall stage (OR 0.45, 95% CI 0.29-0.72, p = 0.001). CONCLUSION: An increased CD9 expression was associated with favorable survival in cancer patients suggesting that CD9 expression could be a valuable survival factor in cancer patients.

Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers.

Lineage tracing in mice indicates that LGR5 is an adult stem cell marker in multiple organs, such as the intestine, stomach, hair follicles, ovary, and mammary glands. Despite many studies exploring the presence of LGR5 cells in human tissues, little is known about its expression profile in either human mammary tissue or pathological lesions. In this study we aim to investigate LGR5 expression in normal, benign, and malignant lesions of the human breast using RNA in situ hybridization. LGR5 expression has not been observed in normal lactiferous ducts and terminal duct lobular units, whereas LGR5-positive cells have been specifically observed in the basal myoepithelium of ducts in the regenerative tissues, ductal carcinoma in situ, and in ducts surrounded by invasive cancer cells. These findings suggest LGR5 marks facultative stem cells that are involved in post injury regeneration instead of homeostatic stem cells. LGR5 positivity was found in 3% (9 of 278 cases) of invasive breast cancers (BC), and it showed positive associations with higher histologic grades (P = 0.001) and T stages (P < 0.001), while having negative correlations with estrogen receptor (P < 0.001) and progesterone receptor (P < 0.001) expression. Remarkably, all LGR5-positive BC, except one, belong to triple-negative BC (TNBC), representing 24% (9 of 38 cases) of all of them. LGR5 histoscores have no correlations with EGFR, CK5/6, Ki-67, or P53 expression. Additionally, no ß-catenin nuclear localization was observed in LGR5-positive BC, indicating that canonical Wnt pathway activation is less likely involved in LGR5 expression in BC. Our results demonstrate that LGR5 expression is induced in regenerative conditions in the myoepithelium of human mammary ducts and that its expression is only observed in TNBC subtype among all invasive BC. Further studies regarding the functional and prognostic impact of LGR5 in TNBC are warranted.

Genetic Parameters for Different Measures of Feed Efficiency and Their Relationship to Production Traits in Three Purebred Pigs.

Residual feed intake (RFI) gained attention as a potential alternative to the feed conversion ratio (FCR). Thus, this study aimed to estimate genetic parameters for different feed efficiency (FE) traits (FCR, RFI1 to RFI5) and their genetic correlation to on-test daily weight gain (ADG), backfat (BFT), loin muscle area (LMA), lean percentage (LP), and total feed intake (FI) for 603 Male Duroc (DD), 295 Landrace (LL), and 341 Yorkshire (YY). The common spatial pen effect was also estimated in these traits. Five RFI measures were estimated by regressing daily feed intake on initial testing age (ITA), initial testing weight (IBW), and ADG for RFI1; other models were the same as RFI1 except for additional BFT for RFI2; LMA for RFI3; BFT and LMA for RFI4; BFT, LMA, and average metabolic body weight (AMBW) instead of IBW for RFI5. Genetic parameters estimated using two animal models and the REML method showed moderate heritability for FCR in all breeds (0.22 and 0.28 for DD, 0.31 and 0.39 for LL, 0.17 and 0.22 for YY), low heritability for the majority of RFI measures in DD (0.15 to 0.23) and YY (0.14 to 0.20) and moderate heritability for all RFI measures in LL (0.31 to 0.34). Pen variance explained 7% to 22% for FE and 0% to 9% for production traits' phenotypic variance. The genetic correlation revealed that selection against less complex RFI1 in DD and LL and RFI2 in YY would bring the most advantageous reduction to FI (0.71 for DD, 0.49 for LL, 0.43 YY) without affecting ADG in all breeds (0.06 for DD, -0.11 for LL, 0.05 for YY), decrease in BFT, and increase in LP in DD (0.51 in BFT, -0.77 in LP) and LL (0.45 in BFT, -0.83 in LP). Therefore, inclusion of these breed-specific RFI measures in the future selection criteria would help improve feed efficiency in the swine industry.

The Intestinal Stem Cell Marker SMOC2 Is an Independent Prognostic Marker Associated With Better Survival in Gastric Cancer.

BACKGROUND/AIM: SPARC-related modular calcium-binding protein 2 (SMOC2), a secreted matricellular protein, is reported to be involved in cancer progression such as cell cycle, angiogenesis, and invasion. In this study, we aimed to investigate the expression of SMOC2 in various gastric lesions and assessed its prognostic value in a large cohort of gastric cancer (GC) patients. PATIENTS AND METHODS: SMOC2 mRNA levels were measured by quantitative real-time PCR using 26 matched fresh-frozen GC samples. SMOC2 protein expression was determined by immunohistochemistry on tissue microarrays including 734 GC specimens and its correlations with clinicopathological features and survival were evaluated. RESULTS: The transcription level of SMOC2 was higher in GC samples compared to normal mucosa (p=0.006). Its expression levels were associated with the intestinal stem cell (ISC) marker, LGR5, but there were no correlations with EPHB2 and OLFM4 or the candidate cancer stem cell markers CD133 and CD44. SMOC2 expression was significantly increased in the intestinal metaplasia and was further increased in gastric adenomas and early gastric cancers (EGC). In total, 34% of GCs were positive for SMOC2, and SMOC2 positivity was higher in old (p=0.001) and male (p<0.001) patients, and in well-differentiated GC (p<0.001). SMOC2 expression had a negative association with perineural invasion (p<0.001) and tumor stage (p<0.001). In survival analysis, SMOC2-positive GC patients had much better clinical outcomes in overall survival rates (p<0.001) compared to SMOC2-negative GC patients. The prognostic impact of SMOC2 remained significant both in intestinal (p<0.001) and diffuse-type GC (p<0.001). Remarkably, a multivariate analysis demonstrated SMOC2 as an independent prognostic marker [hazard ratio (HR)=0.732, p=0.045] along with venous invasion (p=0.012), tumor stage (p<0.001) and CDX2 (p=0.028). CONCLUSION: Our results suggest that SMOC2 can be a prognostic marker for better clinical outcomes in GC.