Profiling of Tumor Microenvironment Components Identifies Five Stroma-Related Genes with Prognostic Implications in Colorectal Cancer.

Background: Tumor microenvironment (TME) significantly affects colorectal cancer (CRC) progression and therapeutic efficacy, particularly the infiltrating stromal components. This study profiled the TME composition of tumor tissue and identify TME-related, especially stroma-related genes having prognosis value in CRC patients. Materials and Methods: We used the ESTIMATE algorithm to assess stromal/immune component and divided 524 CRC cases of public dataset into high- and low-score groups. We analyzed the effect of the score on prognosis and extracted the differential expression genes (DEGs) between groups, which were stromal- and/or immune-related genes, and performed a prognostic investigation of the DEGs. Results: Higher stromal score correlated with poor survival, whereas the immune score was the inverse. By comparing global gene expression of cases with high vs. low stromal/immune scores, we extracted 474 stroma-related genes, 76 immune-related genes, and 498 intersection genes, which were explored by function enrichment and survival analysis. We identified the expression of five stroma-related genes (including ITGA7, PTPN14, SCG2, TNS1, and GRP) significantly associated with poorer survival, which were validated in the other two independent CRC cohorts. Conclusion: These results presented a comprehensive understanding of TME components and identified five stroma-related genes that predict poor outcomes in CRC patients.

A single-cell atlas of liver metastases of colorectal cancer reveals reprogramming of the tumor microenvironment in response to preoperative chemotherapy.

Metastasis is the primary cause of cancer-related mortality in colorectal cancer (CRC) patients. How to improve therapeutic options for patients with metastatic CRC is the core question for CRC treatment. However, the complexity and diversity of stromal context of the tumor microenvironment (TME) in liver metastases of CRC have not been fully understood, and the influence of stromal cells on response to chemotherapy is unclear. Here we performed an in-depth analysis of the transcriptional landscape of primary CRC, matched liver metastases and blood at single-cell resolution, and a systematic examination of transcriptional changes and phenotypic alterations of the TME in response to preoperative chemotherapy (PC). Based on 111,292 single-cell transcriptomes, our study reveals that TME of treatment-naïve tumors is characterized by the higher abundance of less-activated B cells and higher heterogeneity of tumor-associated macrophages (TAMs). By contrast, in tumors treated with PC, we found activation of B cells, lower diversity of TAMs with immature and less activated phenotype, lower abundance of both dysfunctional T cells and ECM-remodeling cancer-associated fibroblasts, and an accumulation of myofibroblasts. Our study provides a foundation for future investigation of the cellular mechanisms underlying liver metastasis of CRC and its response to PC, and opens up new possibilities for the development of therapeutic strategies for CRC.

Loss of CD15 expression in clear cell renal cell carcinoma is correlated with worse prognosis in Chinese patients.

PURPOSE: To explore the role of CD15 expression in the prognosis of clear cell renal cell carcinoma (ccRCC) in Chinese patients. METHODS: The study included 301 patients who had undergone surgery for localized ccRCC. All paraffin-embedded tumor sections were collected to make a set of tissue microarrays. CD15 expression was assessed by immunohistochemistry. The relationship between CD15 expression and survival parameters, clinicopathology features was assessed. Kaplan-Meier and Cox proportional hazards model were utilized to determine the correlation between CD15 expression and overall survival (OS). RESULTS: The median follow-up time was 54.6 months (range, 3-121 months). The positive rate of CD15 expression was 81.7% (246/301). The cut-off value of CD15 expression was defined as the maximum for Youden index by plotting the receiver operating characteristic curve for survival status. As the threshold was 0.5, all cases were divided into two groups: positive expression group and negative expression group. In correlation analysis, loss of CD15 expression was correlated with female gender, higher Fuhrman nuclear grade, with sarcomatoid differentiation, with necrosis, and with vascular invasion. Kaplan-Meier analysis indicated that the OS time of patients with loss of CD15 expression was shorter than that of patients with positive CD15 expression (P = 0.013). CONCLUSION: CD15 is a significant prognostic factor in clear cell renal cell carcinoma.