Concomitant expression patterns of CDX2 and SATB2 as prognostic factors in stage III colorectal cancers.

CDX2 and SATB2 are often used as biomarkers for identification of colorectal origin in primary or metastatic adenocarcinomas. Loss of CDX2 or SATB2 expression has been associated with poor prognosis in patients with colorectal cancer (CRC). However, little is known regarding clinicopathological features, including prognosis, of CRCs with concomitant loss of CDX2 and SATB2. A total of 431 stage III CRCs were analyzed for their expression status in CDX2 and SATB2 using tissue microarray-based immunohistochemistry and expression status was correlated with clinicopathological variables, molecular alterations, and survival. CDX2-negative (CDX2-) CRCs and SATB2-negative (SATB2-) CRCs were found in 8.1 % and 17.2 % of CRCs, respectively, whereas both CDX2-negative and SATB2-negative (CDX2-/SATB2-) CRCs comprised 3.2 % of the CRCs. On survival analysis, neither CDX2-/SATB2+ nor CDX2+/SABT2- CRCs but CDX2-/SATB2- CRCs were associated with poor prognosis. CDX2-/SATB2- CRCs showed significant associations with tumor subsite of right colon, poor differentiation, decreased expression of CK20, aberrant expression of CK7, CIMP-high, MSI-high, and BRAF mutation. In summary, our results suggest that concomitant loss of CDX2 and SATB2 is a prognostic biomarker but isolated loss of CDX2 or SATB2 is not a prognostic biomarker for stage III CRCs.

Prognostic significance of STING expression in solid tumor: a systematic review and meta-analysis.

Objective: Stimulator of interferon genes (STING) is a key regulator in initiating innate immune response from sensing cytosolic DNA. Recent studies have revealed that the cGAS-STING signaling pathway has a crucial role in tumor development and progression across cancer types. Herein, we conducted a meta-analysis to explore the relationship between the immunoexpression of STING and the survival outcome of patients in various solid tumors. Studies relevant to the subject were searched from PubMed, Embase, and Web of Science. Results: Eleven studies including 2,345 patients were eligible for the analysis. STING expression in tumor cells was related to improved disease-free survival/recurrence-free survival (DFS/RFS) (HR = 0.656, 95% CI = 0.455-0.946, p = 0.024) but not with overall survival (OS) (HR = 0.779, 95% CI = 0.534-1.136, p = 0.194). STING expression in stromal cells, however, did not show significant correlation with DFS/RFS and OS (HR = 0.979, 95% CI = 0.565-1.697, p-value = 0.940 and HR = 1.295, 95% CI = 0.845-1.985, p = 0.235, respectively). In a subgroup analysis, STING expression in tumor cells was associated with better DFS (HR = 0.622, 95% CI = 0.428-0.903, p = 0.012). In tumor cells, favorable DFS/RFS were also related to studies from univariate analysis and the gastrointestinal system (HR = 0.667, 95% CI = 0.482-0.923, p = 0.015 and HR = 0.566, 95% CI = 0.330-0.971, p = 0.039). Conclusions: STING expression in tumor cells is associated with favorable outcome in solid tumors. Systematic review registration: https://www.crd.york.ac.uk/prospero/, registration number: CRD42023427027.

Methylation statuses of NCOR2, PARK2, and ZSCAN12 signify densities of tumor-infiltrating lymphocytes in gastric carcinoma.

Individual cell types of human tissues have their own CpG site methylation profiles, which might be utilized for the development of methylation markers to denote tumor-infiltrating lymphocytes (TILs). We aimed to develop DNA methylation markers that recapitulate the densities of TILs in gastric carcinoma (GC). Through genome-wide methylation profiling, NCOR2, PARK2, and ZSCAN12 were found to be highly methylated in CD3-positive and CD8-positive cells and rarely methylated in tumor cells. Scores of the three methylation markers were analyzed for their relationship with the overall survival and recurrence-free survival of patients with advanced GC (n = 471). The scores of three methylation markers were closely associated with densities of CD3-positive or CD8-positive cells at the tumor center or invasive front of GCs and found to be a significant prognostic factor in univariate analysis of overall survival and recurrence-free survival. In multivariate analysis, the highest score showed hazard ratios of 0.513 (CI 0.306-0.857) and 0.434 (CI 0.261-0.720) for overall survival and recurrence-free survival, respectively. The findings suggest that methylation markers signifying TILs might be utilized for the recapitulation of TIL density in GCs and serve as biomarkers for predicting prognosis in patients with GC.

Combinatory statuses of tumor stromal percentage and tumor infiltrating lymphocytes as prognostic factors in stage III colorectal cancers.

BACKGROUND AND AIM: Tumor stroma and tumor-infiltrating lymphocytes (TILs) are major constituents of the tumor microenvironment, although they have different effects on the prognosis of patients with colorectal cancer (CRC). Combinatory statuses of tumor-stromal percentage (TSP) and TILs are expected to provide more powerful prognostic information but have never been studied in CRCs. METHODS: Stage III CRCs from patients (n = 487) treated with adjuvant chemotherapy were assessed for their TSP and CD3-TIL or CD8-TIL densities using computer-aided methodology. With cut-off values set at median values for intraepithelial TIL (iTIL) and stromal TIL (sTIL) densities, CRCs were sorted into low and high iTIL or sTIL groups. CRCs were classified into five quintile (Q1-Q5) groups according to their TSP and divided into high TSP (Q5) and low TSP (Q1-4) groups. RESULTS: The combination of CD8 iTIL density and TSP was found to be an independent prognostic parameter in multivariate survival analysis in terms of cancer-specific survival and recurrence-free survival. CRCs with low CD8 iTIL density and high TSP showed the worst survival. The combinatory status showed more prognostic power than CD8 iTIL density or TSP alone. Multivariate survival analysis in an independent cohort of stage III CRC validated the prognostic power of the combinatory statuses. CONCLUSIONS: The findings suggest that the combinatory status might serve as a prognostic parameter in stage III CRCs. Further research in a large-scale cohort of patients with stage III CRC is needed to validate the prognostic power of the combinatory status.