Esophageal squamous cell carcinoma (ESCC) is the sixth most common cause of cancer-related mortality worldwide, with more than half of them occurred in China. Radiotherapy (RT) has been widely used for treating ESCC. However, radiation-induced DNA damage response (DDR) can promote the release of cytokines and chemokines, and triggers inflammatory reactions and changes in the tumor microenvironment (TME), thereby inhibiting the immune function and causing the invasion and metastasis of ESCC. Radioresistance is the major cause of disease progression and mortality in cancer, and it is associated with heterogeneity. Therefore, a better understanding of the radioresistance mechanisms may generate more reversal strategies to improve the cure rates and survival periods of ESCC patients. We mainly summarized the possible mechanisms of radioresistance in order to reveal new targets for ESCC therapy. Then we summarized and compared the current strategies to reverse radioresistance.

Background: To investigate the expression and function of RSK4, MMP-9 and CD44 in primary clear cell renal cell carcinoma (primary ccRCC) and metastatic clear cell renal cell carcinoma (metastatic ccRCC), as well as the correlation with clinicopathological features of patients. Method: The expression levels of RSK4, CD44 and MMP-9 in 52 primary ccRCC samples and 48 metastatic ccRCC samples were detected by immunohistochemistry, and the relationship between RSK4, CD44 and MMP-9 expression and clinicopathological features as well as prognosis of metastatic ccRCC patients was statistically analysed. Ectopic RSK4 expression in ccRCC cell lines was performed to determine its effect on cell cycle regulation, tumour invasiveness, and metastatic capability. Results: The positive rates of RSK4, MMP-9 and CD44 expression in metastatic ccRCC tissues were 75, 68.75 and 91.7%, respectively, while the rates in primary ccRCC tissues were 44.2, 34.6 and 69.2%, respectively. Thus, the positive rates in metastatic ccRCC were higher than those in primary ccRCC (P_RSK4 = 0. 002; P_MMP-9 = 0. 002; P_CD44 = 0. 001). However, the expression of RSK4, CD44 and MMP-9 was unrelated to age, gender, or metastatic sites (P > 0.05) but was related to WHO/ISUP nucleolar grade (P_RSK4 = 0.019; P_CD44 = 0.026; P_MMP-9 = 0.049). In metastatic ccRCC, expression among the three proteins showed a positive correlation (P = 0.008). Moreover, expression between RSK4 and CD44 (P = 0.019) and MMP-9 and CD44 (P = 0.05) also showed positive correlations, whereas RSK4 and MMP-9 showed no significant correlation (P = 1.00). Molecular studies showed that overexpression of RSK4 could enhance the invasive and migratory abilities of ccRCC cell lines through the regulation of CD44 and MMP-9 expression and vice versa. Conclusions: The overexpression of RSK4, MMP-9 and CD44 is associated with the invasion and metastasis of ccRCC, indicating that they could be potential prognostic factors and serve as new potential therapeutic targets for ccRCC.

Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Twenty-five patients with GI-DLBCL were enrolled in the genetic mutation analysis with a median of 184 (range 79–382) protein-altering variants per patient. We identified recurrent oncogenic mutations in GI-DLBCL, including those in TP53, MUC16, B2M, CCND3, HIST1H1C, NEB, and ID3. Compared with nodal DLBCL, GI-DLBCL exhibited an increased mutation frequency of TP53 and reduced mutation frequencies of PIM1, CREBBP, BCL2, KMT2D, and EZH2. Moreover, GI-DLBCL exhibited fewer MYD88 and CD79B mutations than DLBCL in the testis and central nervous system. GI-DLBCLs with HLA-B, MEF2A, RHOA, and NAV3 mutations exhibited a tendency toward a high proliferation index. MUC16 and ETV6 mutations often occurred in tumors with early clinical staging. Our data provide a comprehensive understanding of the landscape of mutations in a small subset of GI-DLBCLs. The genetic mutation profiles of GI-DLBCL differ from those of nodal DLBCL and DLBCL in immune-privileged sites. The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL.