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Introduction The purpose was to evaluate the effect of adjuvant radiation therapy on the survival prognosis of older women with early-stage breast cancer under different surgical treatments. Methods We collected patients from the Surveillance, Epidemiology and End Results (SEER) database. Elderly female patients (≥ 70 years) with stage I–IIB diagnosed with invasive carcinoma in 1988–2017 were included. After propensity score matching (PSM), the prognosis of patients who underwent breast-conserving surgery or mastectomy was calculated separately. The effects of radiotherapy on the survival of three special population groups (breast-conserving surgery + T1N0M0 + ER positive, mastectomy + T3N0M0 and mastectomy + T1-2N1M0) were analyzed selectively. Results Of 106,553 older women with early-stage breast cancer were identified. 48,630 patients had received radiotherapy, while 57,923 patients had not. After PSM, older women undergoing breast-conserving surgery benefited significantly from radiotherapy (both OS and BCSS p p p p = 0.0907). While in the subgroup of T3N0M0 breast cancer treated by mastectomy, survival analyses showed no statistical differences between patients receiving radiation or not (OS p = 0.1778, BCSS p = 0.6957). Conclusions This study indicated the clinical effects of radiation on older women who received different surgical treatments. Our study suggested that radiotherapy should be omitted in older women undergoing mastectomy + T3N0M0 or T1-2N1M0 and radiotherapy could be considered in women with T1N0M0 + ER-positive undergoing breast-conserving surgery.

BackgroundGlioma is the most malignant cancer in the brain. As a major vitamin-K-dependent protein in the central nervous system, PROS1 not only plays a vital role in blood coagulation, and some studies have found that it was associated with tumor immune infiltration. However, the prognostic significance of PROS1 in glioma and the underlying mechanism of PROS1 in shaping the tumor immune microenvironment (TIME) remains unclear.MethodsThe raw data (including RNA-seq, sgRNA-seq, clinicopathological variables and prognosis, and survival data) were acquired from public databases, including TCGA, GEPIA, CGGA, TIMER, GEO, UALCAN, and CancerSEA. GO enrichment and KEGG pathway analyses were performed using “cluster profiler” package and visualized by the “ggplot2” package. GSEA was conducted using R package “cluster profiler”. Tumor immune estimation resource (TIMER) and spearman correlation analysis were applied to evaluate the associations between infiltration levels of immune cells and the expression of PROS1. qRT-PCR and WB were used to assay the expression of PROS1. Wound-healing assay, transwell chambers assays, and CCK-8 assays, were performed to assess migration and proliferation. ROC and KM curves were constructed to determine prognostic significance of PROS1 in glioma.ResultsThe level of PROS1 expression was significantly increased in glioma in comparison to normal tissue, which was further certificated by qRT-PCR and WB in LN-229 and U-87MG glioma cells. High expression of PROS1 positively correlated with inflammation, EMT, and invasion identified by CancerSEA, which was also proved by downregulation of PROS1 could suppress cells migration, and proliferation in LN-229 and U-87MG glioma cells. GO and KEGG analysis suggested that PROS1 was involved in disease of immune system and T cell antigen receptor pathway. Immune cell infiltration analysis showed that expression of PROS1 was negatively associated with pDC and NK CD56 bright cells while positively correlated with Macrophages, Neutrophils in glioma. Immune and stromal scores analysis indicated that PROS1 was positively associated with immune score. The high level of PROS1 resulted in an immune suppressive TIME via the recruitment of immunosuppressive molecules. In addition, Increased expression of PROS1 was correlated with T-cell exhaustion, M2 polarization, poor Overall-Survival (OS) in glioma. And it was significantly related to tumor histological level, age, primary therapy outcome. The results of our experiment and various bioinformatics approaches validated that PROS1 was a valuable poor prognostic marker.ConclusionIncreased expression of PROS1 was correlated with malignant phenotype and associated with poor prognosis in glioma. Besides, PROS1 could be a possible biomarker and potential immunotherapeutic target through promoting the glioma immunosuppressive microenvironment and inducing tumor-associated macrophages M2 polarization.

Background Sentinel lymph node dissection (SLND) is an alternative to axillary lymph node dissection (ALND) for breast cancer surgery. But the criteria of SLND only for patients with limited disease in the sentinel node is disputed. Methods From the Surveillance, Epidemiology, and End Results (SEER) database, 2000–2015, we identified 97,296 early breast cancer females with 1–3 axillary lymph nodes macro-metastasis. Of them, 1–5 (axillary conservation group), 6–9, and ≥ 10 (ALND group) axillary lymph nodes were dissected in 28,639, 16,838, and 51,819 patients, respectively. According to the criteria of the ACOSOG Z0011 trial, two historical cohort studies of patients who underwent lumpectomy or mastectomy were conducted and the survival outcomes between ALND and axillary conservation were compared. Results Overall, dissection of 6–9 regional lymph nodes resulted in the worst prognosis. After propensity-matched analysis, it was found that patients in the axillary conservation group had worse survival than the ALND group in overall survival. No significant difference in prognosis between the group undergoing lumpectomy was found both in OS and BCSS. Subgroup analysis revealed that Grade 3, T2, two lymph nodes positive, or Her2 positive were the main causes of worse survival in the axillary conservation group. Conclusion Not all patients with N1 early breast cancer suit axillary conservation. Axillary conservation was sufficient in patients who were treated with lumpectomy. ALND cannot be omitted in patients who were ineligible for the Z0011 and undergoing mastectomy with the following characteristics: T2, Grade 3, two positive lymph nodes, and Her2 positive, which may be better complemented to the Z0011 trial. Hence, under different surgical methods, the clinical precision treatment of ALND or axillary preservation is essential.

Kidney renal clear cell carcinoma (KIRC or ccRCC) is the most notorious subtype of renal cell carcinoma for its poor prognosis. Mounting evidence has highlighted the key role of PRKCE in the initiation and development of several types of human cancer, including kidney renal clear cell carcinoma (KIRC). However, the mechanism of PRKCE aberrant expression and the specific clinical correlation of PRKCE expression with immune cell infiltration in KIRC remains elusive. Therefore, we analyzed the relationship between PRKCE and KIRC using many databases, including Oncomine, TCGA, GTEx, TIMER, and GEO. We found that PRKCE decreased in KIRC tumor tissue compared to normal tissue. The Kaplan-Meier Plotter analysis and Univariate and Multivariate Cox analyses were used to evaluate the association between PRKCE and clinicopathological variables and prognosis. Low PRKCE expression was associated with poor survival and histologic grade, T stage, pathologic stage, and M stage. Besides, the C-indexes and calibration plots of the nomogram based on multivariate analysis showed an effective predictive performance for KIRC patients. In addition, PRKCE may be positively correlated with inflammation and negatively correlated with proliferation, metastasis, and invasion as identified by CancerSEA. Moreover, overexpression of PRKCE suppressed ACHN and Caki-1 cell proliferation, migration, and invasion in vitro. Additionally, methylation level data acquired from UALCAN, DiseaseMeth, CCLE, LinkedOmics, and MEXPRESS was used to investigate the relationship between PRKCE expression and PRKCE methylation level. Furthermore, upstream potential miRNA predictions were further performed to explore the mechanism of PRKCE decreased expression in KIRC using multiple online databases available on publicly assessable bioinformatics platforms. High PRKCE methylation levels and hsa-miR-21-5p may contribute to PRKCE low expression in KIRC. Finally, an analysis of immune infiltration indicated that PRKCE was associated with immune cell infiltration. Importantly, PRKCE may affect prognosis partially by regulating immune infiltration in KIRC. In summary, PRKCE may serve as a novel prognostic biomarker reflecting immune infiltration level and a novel therapeutic target in KIRC.

Background: Tumor stemness-related genes promote tumor progression and resistance to immunotherapy, but the relation between tumor-infiltrating immune cells and colon adenocarcinoma (COAD) stemness-related genes remains unclear. Methods: The mRNAsi scores, a stemness index derived from transcriptomic data of the TCGA COAD cohort were used for integrated bioinformatics analysis. The Weighted Gene Co-expression Network Analysis (WGCNA) was applied to classify the modules correlated with mRNAsi scores. The Gene Expression Omnibus (GEO) cohorts GSE76402 was used to verify the DEGs between colon cancer and normal tissues. Real-time PCR and Flow-cytometry were used to validate the expression of genes and cancer stem cells marker in the spheres of colon cancer cells. The Single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT algorithm were used to explore the correlation between significant genes and the immune cells in tumor microenvironment. Result: The mRNAsi score was associated with tumor development and progression. TTK were identified as COAD stemness-related genes based on WGCNA analysis. TTK were negatively correlated with immunity. Interestingly, M1 Macrophages had a higher infiltration in COAD with high TTK expression. Higher infiltration of M1 Macrophages would result in the worse survival rate of COAD patients. Conclusion: TTK may have the potential as a prognostic biomarker and adjuvant target to promote immunotherapy sensitivity and improve outcomes of COAD patients.