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Objective: Polo‐like kinase 1 (PLK1), a serine/threonine‐protein kinase, functions as a potent oncogene in the initiation and progression of tumor. The aim of this study is to assess potential correlations between PLK1 expression and immune infiltration in breast cancer (BRCA) and construct a PLK1‐based immune risk model applicable for prognosis and treatment response prediction in BRCA. Methods: We collected data on PLK1 gene expression in BRCA patients from The Cancer Genome Atlas (TCGA) database. Thereafter, we analyzed the associations of PLK1 expression with immune cell infiltration and immunomodulators, and established a prognostic risk model based on seven PLK1‐associated immunomodulator genes and a nomogram for survival prediction. Results: BRCA prognosis, clinical stage progression, and tumor classification were all shown to be substantially correlated with PLK1 expression. The PLK1 gene was significantly enriched in T cell and B cell receptors and molecules of the chemokine signaling pathways. Specifically, PLK1 expression was positively correlated with the CD8+ T cell and regulatory T cell (Tregs) activation and negatively correlated with M2 macrophage infiltration. The seven‐genes‐based risk model could serve as an independent prognostic factor of BRCA. The risk model was markedly correlated with the expression of programmed cell death protein 1/programmed cell death ligand 1 (PD‐1/PD‐L1; both p < 0.001) immune checkpoints, and tumor mutation burden (TMB). High‐ and low‐risk BRCA patients identified by the risk model responded differently to anti‐PD‐1 and/or anti‐CTLA4 therapy, as well as common chemotherapy drugs, like cisplatin, paclitaxel, and gemcitabine. Conclusion: This PLK1‐based immune risk model can effectively predict the prognosis and tumor progression of BRCA, identify gene mutations, and evaluate patient's response toward immunotherapy and chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Background and Aim: The spatial distribution and interactions of cells in the tumor immune microenvironment (TIME) might be related to the different responses of triple‐negative breast cancer (TNBC) to immunomodulators. The potential of multiplex IHC (m‐IHC) in evaluating the TIME has been reported, but the efficacy is insufficient. We aimed to research whether m‐IHC results could be used to reflect the TIME, and thus to predict prognosis and complement the TNBC subtyping system. Methods: The clinical, imaging, and prognosis data for 86 TNBC patients were retrospectively reviewed. CD3, CD4, CD8, Foxp3, PD‐L1, and Pan‐CK markers were stained by m‐IHC. Particular cell spatial distributions and interactions in the TIME were evaluated with the HALO multispectral analysis platform. Then, we calculated the prognostic value of components of the TIME and their correlations with TNBC transcriptomic subtypes and MRI radiomic features reflecting TNBC subtypes. Results: The components of the TIME score were established by m‐IHC and demonstrated positive prognostic value for TNBC (p = 0.0047, 0.039, <0.0001 for DMFS, RFS, and OS). The score was calculated from several indicators, including Treg% in the tumor core (TC) or stromal area (SA), PD‐L1+ cell% in the SA, CD3 + cell% in the TC, and PD‐L1+/CD8+ cells in the invasive margin and SA. According to the TNBC subtyping system, a few TIME indicators were significantly different in different subtypes and significantly correlated with MRI radiomic features reflecting TNBC subtypes. Conclusion: We demonstrated that the m‐IHC‐based quantitative score and indicators related to the spatial distribution and interactions of cells in the TIME can aid in the accurate diagnosis of TNBC in terms of prognosis and classification. [ABSTRACT FROM AUTHOR]

Background: Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR‐125b‐2‐3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR‐125b‐2‐3p in advanced CRC under chemotherapy have yet to be elucidated. Methods: MiR‐125b‐2‐3p expression was detected by real‐time PCR (RT‐PCR) in CRC tissues. The effects of miR‐125b‐2‐3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR‐125b‐2‐3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on. Results: MiR‐125b‐2‐3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR‐125b‐2‐3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR‐125b‐2‐3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR‐125b‐2‐3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR‐125b‐2‐3p inhibited the proliferation and epithelial‐mesenchymal transition (EMT) of CRC induced by lncRNA XIST. Conclusions: Lower miR‐125b‐2‐3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR‐125b‐2‐3p to mediate WEE1 expression. LncRNA XIST‐miR‐125b‐2‐3p‐WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC. [ABSTRACT FROM AUTHOR]

Purpose: Tissue carcinoembryonic antigen (t‐CEA) and serum carcinoembryonic antigen (s‐CEA) expression profiles are the most useful tumor markers for the diagnosis and evaluation of colorectal cancer (CRC) worldwide; however, their roles in CRC progression remain controversial. This study aimed to compare the prognostic values of both s‐CEA and t‐CEA in CRC. Methods: A total of 517 patients from January 2006 to December 2010 with stages I‐III CRC were retrospectively examined, with 5‐year postoperative follow‐up and death as end‐points. T‐CEA expression, s‐CEA expression, and clinical pathological parameters were inputted into the SPSS 21.0 software. The Kaplan‐Meier method was used to analyze the 5‐year disease‐free survival (DFS) rate of patients in different tumor node metastasis (TNM) stages based on t‐CEA and s‐CEA expression. Results: Tumor differentiation and the number of positive lymph node harvests were significantly different among the t‐CEA groups (P < 0.001, P = 0.002); however, clinicopathological features showed no significant difference. The groups with high s‐CEA and t‐CEA expression had a significantly poorer prognosis than those with low s‐CEA (P = 0.021) and t‐CEA (P < 0.01) expression, respectively. The multivariate analysis demonstrated that t‐CEA was an independent prognostic factor in CRC (P < 0.001), but s‐CEA was not (P = 0.339). The 5‐year disease‐free survival rates among the t‐CEA groups were significantly different in stages I, II, and III of CRC (P = 0.001, P < 0.001, P < 0.001), whereas in the s‐CEA groups, this difference was observed only in stage III (P = 0.014). Conclusion: This study shows that postoperative t‐CEA expression is an independent factor associated with poorer CRC prognosis and has a higher prognostic value than that of preoperative s‐CEA expression. Tissue carcinoembryonic antigen (t‐CEA)expression and serum carcinoembryonic antigen (s‐CEA) expression of colorectal carcinoma (CRC) are the most useful tumor markers for the diagnosis and evaluation of prognosis, but the role remains controversial. The objective of this study was to compare the prognostic value of CEA both in serum and tumor tissue in CRC. [ABSTRACT FROM AUTHOR]