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Triple-negative breast cancer (TNBC) has an aggressive biological behavior and poor outcome. Our published study showed that PAI-1 could induce the migration and metastasis of TNBC cells. However, the underlying mechanism by which PAI-1 regulates TNBC metastasis has not been addressed. Here, we demonstrated that PAI-1 is high expressed in TNBC and promotes TNBC cells tumorigenesis. Using microarray analysis of lncRNA expression profiles, we identified a lncRNA SOX2-OT, which is induced by PAI-1 and could function as an oncogenic lncRNA in TNBC. Mechanistic analysis demonstrated that SOX2-OT acts as a molecular sponge for miR-942-5p to regulate the expression of PIK3CA, ultimately leading to activating PI3K/Akt signaling pathway and promoting TNBC metastasis. Taken together, our findings suggest that SOX2-OT regulates PAI-1-induced TNBC cell metastasis through miR-942-5p/PIK3CA signaling and illustrate the great potential of developing new SOX2-OT-targeting therapy for TNBC patients.

Background Cancer immunotherapies have achieved great progress in colorectal cancer (CRC). However, only a small subset of CRC patients with microsatellite instability (MSI) can obtain benefits from immune checkpoint inhibitors (ICIs). Nearly 85% of all CRC patients have microsatellite-stable (MSS) disease, which does not respond to ICIs. Increasing evidence has revealed that CD14 promotes tumor growth and induces an immunosuppressive environment through CD14+ immunosuppressive cells. However, a systematic exploration of CD14 in CRC is lacking. Method A total of 644 samples with transcriptome data and 566 samples with microarray data were investigated in this study, including TCGA RNA-Seq and GSE39582 microarray. R software was the main tool for graphical work and statistical analysis. Results CD14 was upregulated in the MSI-H, BRAF-mutant, right-sided disease, and hypermethylation groups. Cases with high CD14 expression were related to the CMS4 subtype and had frequent mutation of driver oncogenes. CD14 expression was associated with the regulation of immune system processes in gene ontology analysis. The cytokine-cytokine receptor interaction was associated with CD14 expression. Moreover, CD14 was associated with high immune and stromal infiltration, and CD14 synergized with immune checkpoints. Additionally, CD14 was involved in immune and inflammatory responses. Finally, high CD14 expression predicted worse outcomes and was an independent negative indicator of prognosis in CRC, which was further confirmed in tissue microarray. Conclusion Our findings indicated that CD14 expression was associated with specific clinical characteristics. High CD14 expression might represent pre-existing immunity and have a high correlation with immune checkpoints. Moreover, CD14 correlated with poor clinical outcomes in CRC. Therefore, the CD14 molecule promises to be a potential target to enhance the immunotherapy of colorectal cancers.

Background Previous studies have demonstrated that left-sided tumors have better prognoses than right-sided tumors in RAS wild-type mCRC (metastatic colorectal cancer) patients, while anti-EGFR mAbs appear to have no advantage compared with bevacizumab for right-sided tumors in these patients. Nevertheless, it remains unclear whether primary tumor location affects patients’ options for potentially curative resection. Methods PubMed, the Cochrane Library, Embase, ASCO, and ESMO conference abstracts were searched. The inclusion criteria were RCT (randomized controlled trials) studies that evaluated the efficacy of anti-EGFR mAbs based on primary tumor location. The outcomes included ORR, ETS, and DpR. ORs for ORR were calculated with 95% confidence intervals by Comprehensive Meta-Analysis, version 2.0. Result Nine studies including nine RCTs were analyzed. Regardless of left- or right-sided tumors, the ORRs for anti-EGFR mAb (left-sided: 80.2%, 95% CI, 47–95%; I2 = 76.9%; right-sided: 46.1%, 95% CI, 39.4–53.0%; I2 = 18.9%) were both higher than the control arm including chemotherapy with or without bevacizumab. The ORs for anti-EGFR mAbs have a significant benefit compared with chemotherapy with or without bevacizumab in left-sided tumors (OR = 2.19, 95% CI, 1.41–3.38; P

Background: The efficacy of oxaliplatin-based chemotherapy combined with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) remains controversial in metastatic colorectal cancer (mCRC). This meta-analysis aims to estimate the effect of adding panitumumab or cetuximab to oxaliplatin-based chemotherapy in RAS wild type mCRC patients for the first-line treatment. The primary tumor location is also considered into this meta-analysis. Methods: RCT studies were identified by a search of MEDLINE, EMBASE, Cochrane library to October 2017, supplemented by manually retrieving ASCO, ESMO conference abstracts. The pooled hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS), and pooled odds ratios (OR) for the overall response rate (ORR) were calculated by Review Manager 5.3. Results: The results indicated that the addition of anti-EGFR mAbs to FOLFOX regimen in RAS wild-type mCRC patients for the first-line treatment resulted in considerable improvements in PFS (HR = 0.70; 95% confidence interval [CI]: 0.59–0.82; P