CCDC137 Is a Prognostic Biomarker and Correlates With Immunosuppressive Tumor Microenvironment Based on Pan-Cancer Analysis

Guo, Lihao; Li, Boxin; Lu, Zhaohong; Hu, Liang; Yang, Hui; Chen, Yuting; Zhu, Shiheng; Zeng, Minjuan; Wei, Yixian; Liu, Tonggong; Jiang, Tikeng; Xuan, Mei Ying; Tang, Huanwen

doi:10.3389/fmolb.2021.674863

Cited by 21 publications

(17 citation statements)

References 21 publications

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“…CCDC137, as one vital member of coiled‐coil domain containing (CCDC) family proteins, was overexpressed and positively associated with worse prognosis in various tumour types, such as liver hepatocellular carcinoma, lower grade glioma and prostate adenocarcinoma. 46 Similarly, we observed that CCDC137 expression was elevated in liver metastatic CRC patients and positively correlated with advanced tumour stages and lymph node metastatic stages of CRC. Furthermore, the overexpressed CCDC137 was significantly correlated with short disease‐free survival as shown in TCGA database.…”

Section: Discussionsupporting

confidence: 57%

CDK12 orchestrates super‐enhancer‐associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer

Dai

Peng

et al. 2022

Clinical & Translational Med

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Background Hepatic metastasis is the primary and direct cause of death in individuals with colorectal cancer (CRC) attribute to lack of effective therapeutic targets. The present study aimed to identify potential druggable candidate targets for patients with liver metastatic CRC. Methods The transcriptional profiles of super‐enhancers (SEs) in primary and liver metastatic CRC were evaluated in publicly accessible CRC datasets. Immunohistochemistry of human CRC tissues was conducted to determine the expression level of CDK12. Cellular proliferation, survival and stemness were examined upon CDK12 inhibition by shCDK12 or a selective CDK12 inhibitor named SR‐4835 with multiple in vitro and in vivo assays. RNA sequencing and bioinformatics analyses were carried out to investigate the mechanisms of CDK12 inhibition in CRC cells. Results We identified CDK12 as a driver gene for direct hepatic metastasis in CRC. Suppression of CDK12 led to robust inhibition of proliferation, survival and stemness. Mechanistically, CDK12 intervention preferentially repressed the transcription of SE‐associated genes. Integration of the SE landscape and RNA sequencing, BCL2L1 and CCDC137 were identified as SE‐associated oncogenic genes to strengthen the abilities of cellular survival, proliferation and stemness, eventually increasing liver metastasis of CRC. Conclusions Our data highlight the potential of CDK12 and SE‐associated oncogenic transcripts as therapeutic targets for patients with liver metastatic CRC.

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Section: Discussionsupporting

confidence: 57%

CDK12 orchestrates super‐enhancer‐associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer

Dai

Peng

et al. 2022

Clinical & Translational Med

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“…TGFβ signaling plays a major role in shaping the immunosuppressive tumor microenvironment [ 80 , 81 ]. Through transduction of IL10-induced signaling, IL10RB (IL10 receptor subunit beta) contributes to the immunosuppressive tumor microenvironment [ 82 , 83 ]. Consistent with this knowledge, BIRC5, MXD3, and RECQL4 expressions positively correlate with IL10RB expression ( Figure 8 ).…”

Section: Resultsmentioning

confidence: 99%

Prediction of Adrenocortical Carcinoma Relapse and Prognosis with a Set of Novel Multigene Panels

Lin

et al. 2022

Cancers

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Effective assessment of adrenocortical carcinoma (ACC) prognosis is critical in patient management. We report four novel and robust prognostic multigene panels. Sig27var25, SigIQvar8, SigCmbnvar5, and SigCmbn_B predict ACC relapse at area under the curve (AUC) of 0.89, 0.79, 0.78, and 0.80, respectively, and fatality at AUC of 0.91, 0.88, 0.85, and 0.87, respectively. Among their 33 component genes, 31 are novel. They could be differentially expressed in ACCs from normal tissues, tumors with different severity (stages and lymph node metastasis), ACCs with TP53 mutations, and tumors with differentially expressed immune checkpoints (CTLA4, PD1, TGFBR1, and others). All panels correlate with reductions of ACC-associated CD8+ and/or NK cells. Furthermore, we provide the first evidence for the association of mesenchymal stem cells (MSCs) with ACC relapse (p = 2 × 10−6) and prognosis (p = 2 × 10−8). Sig27var25, SigIQvar8, SigCmbnvar5, and SigCmbn_B correlate with MSC (spearman r ≥ 0.53, p ≤ 1.38 × 10−5). Sig27var25 and SigIQvar8 were derived from a prostate cancer (PC) and clear cell renal cell carcinoma (ccRCC) multigene signature, respectively; SigCmbnvar5 and SigCmbn_B are combinations of both panels, revealing close relationships of ACC with PC and ccRCC. The origin of these four panels from PC and ccRCC favors their prognostic potential towards ACC.

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“…Accumulated evidence indicated that the fraction of immune cells in the TME could serve as a marker for the diagnosis and prognosis of a variety of malignant tumors ( 48 , 49 ). However, some prognostic models based on the TME were developed in the setting of a pan-cancer analysis ( 50 , 51 ); they might not be the most optimal choice for CM. In addition, not all fractions of the TME exert a significant impact on the prognosis of tumors.…”

Section: Discussionmentioning

confidence: 99%

Core immune cell infiltration signatures identify molecular subtypes and promote precise checkpoint immunotherapy in cutaneous melanoma

Zhu

et al. 2022

Front. Immunol.

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Yutao Wang, China Medical University, ChinaThe tumor microenvironment (TME) has been shown to impact the prognosis of tumors in patients including cutaneous melanoma (CM); however, not all components of TME are important. Given the aforementioned situation, the functional immune cell contents correlated with CM patient prognosis are needed to optimize present predictive models and reflect the overall situation of TME. We developed a novel risk score named core tumor-infiltrating immune cell score (cTICscore), which showed certain advantages over existing biomarkers or TME-related signatures in predicting the prognosis of CM patients. Furthermore, we explored a new gene signature named cTILscore−related module gene score (cTMGs), based on four identified TME-associated genes (GCH1, GZMA, PSMB8, and PLAAT4) showing a close correlation with the cTICscore, which was generated by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis to facilitate clinical application. Patients with low cTMGs had significantly better overall survival (OS, P = 0.002,< 0.001, = 0.002, and = 0.03, respectively) in the training and validating CM datasets. In addition, the area under the curve values used to predict the immune response in four CM cohorts were 0.723, 0.723, 0.754, and 0.792, respectively, and that in one gastric cohort was 0.764. Therefore, the four-gene signature, based on cTICscore, might improve prognostic information, serving as a predictive tool for CM patients receiving immunotherapy.cutaneous melanoma, tumor microenvironment, prognosis, immunotherapy, cTICscore

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CCDC137 Is a Prognostic Biomarker and Correlates With Immunosuppressive Tumor Microenvironment Based on Pan-Cancer Analysis

Cited by 21 publications

References 21 publications

CDK12 orchestrates super‐enhancer‐associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer

CDK12 orchestrates super‐enhancer‐associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer

Prediction of Adrenocortical Carcinoma Relapse and Prognosis with a Set of Novel Multigene Panels

Core immune cell infiltration signatures identify molecular subtypes and promote precise checkpoint immunotherapy in cutaneous melanoma

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