Background: Abnormal expression of suppressor of cytokine signaling (SOCS) proteins regulates tumor angiogenesis and development in cancers. In this study, we aimed to perform a comprehensive bioinformatic analysis of SOCS proteins in breast invasive carcinoma (BRCA). Methods: The gene expression, methylation level, copy number, protein expression and patient survival data related to SOCS family members in BRCA patients were obtained from the following databases: Oncomine, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), PCViz, cBioPortal and Kaplan-Meier plotter. Correlation analyses, identification of interacting genes and construction of regulatory networks were performed by functional and pathway enrichment analyses, weighted gene coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA). Results: Data related to 1109 BRCA tissues and 113 normal breast tissue samples were extracted from the TCGA database. SOCS2 and SOCS3 exhibited significantly lower mRNA expression levels in BRCA tissues than in normal tissues. BRCA patients with high mRNA levels of SOCS3 (p < 0.01) and SOCS4 (p < 0.05) were predicted to have significantly longer overall survival (OS) times. Multivariate analysis showed that SOCS3 was an independent prognostic factor for OS. High mRNA expression levels of SOCS2 (p < 0.001), SOCS3 (p < 0.001), and SOCS4 (p < 0.01), and a low expression level of SOCS5 (p < 0.001) were predicted to be significantly associated with better recurrence-free survival (RFS). Multivariate analysis showed that SOCS2 was an independent prognostic factor for RFS. Lower expression levels of SOCS2 and SOCS3 were observed in patients with tumors of more advanced clinical stage (p < 0.05). Functional and pathway enrichment analyses, together with WGCNA and GSEA, showed that SOCS3 and its interacting genes were significantly involved in the JAK-STAT signaling pathway, suggesting that JAK-STAT signaling might play a critical role in BRCA angiogenesis and development. Western blot results showed that overexpression of SOCS3 inhibited the activity of the JAK-STAT signaling pathway in vitro. Conclusions: SOCS family proteins play a very important role in BRCA. SOCS3 may be a prognostic factor and SOCS2 may be a potential therapeutic target in breast cancer.

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for medullary thyroid cancer (MTC) was implemented in 2018. However, its ability to predict prognosis remains controversial. Patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and multicenter datasets. Overall survival was the primary end-point of the present study. The concordance index (C-index) was used to assess the efficacy of various models to predict prognostic outcomes. A total of 1450 MTC patients were selected from the SEER databases and 349 in the multicenter dataset. According to the AJCC staging system, there were no significant survival differences between T4a and T4b categories (P = .299). The T4 category was thus redefined as T4a’ category (≤3.5 cm) and T4b’ category (>3.5 cm) based on the tumor size, which was more powerful for distinguishing the prognosis (P = .003). Further analysis showed that the T category was significantly associated with both lymph node (LN) location and count (P < .001). Therefore, the N category was modified by combining the LN location and count. Finally, the above-mentioned novel T and N categories were adopted to modify the 8th AJCC classification using the recursive partitioning analysis principle, and the modified staging system outperformed the current edition (C-index, 0.811 vs. 0.792). The 8th AJCC staging system was improved based on the intrinsic relationship among the T category, LN location, and LN count, which would have a positive impact on the clinical decision-making process and appropriate surveillance.

Purpose: The 8th edition of the American Joint Committee on Cancer (AJCC) tumor-lymph node-metastasis (TNM) staging system for gallbladder cancer (GBC) recommended that at least six lymph nodes (LNs) should be examined. But most patients with GBC had fewer than six LNs resected. This study aimed to establish an alternative index for assessing the LN status during the staging system for GBC patients with fewer than six LNs retrieved. Patients and Methods: Patient data was extracted from the Surveillance, Epidemiology, and End Results (SEER) database (cases between 2004 and 2013). X-tile software was used to determine the optimal cutoff value for lymph node ratio (LNR) and a concordance index (C-index) was used to evaluate the discriminatory powers of the two staging systems. Results: The majority of GBC patients in our cohort (1353, 78.5%) had fewer than six LNs examined. Among patients with inadequate LN examination, the higher number of LNs examined correlated with a lower proportion of patients. Using the TNM staging system, the C-index for patients with fewer than six LNs and patients with six or more LNs screened were 0.636 and 0.704, respectively. Using the staging system based on LNR (TNrM), the C-index for patients with fewer than six LNs retrieved and patients with six or more LNs retrieved were 0.649 and 0.694, respectively. Similar results were observed in patients with gallbladder adenocarcinoma (GBA). Conclusion: TNrM might be superior to the 8th AJCC TNM staging system for stratifying GBC patients with fewer than six LNs examined, and it can complement TNM for more accurate risk stratification. Future prospective studies are needed to validate our findings.