Exome-Wide Association Study Identifies Low-Frequency Coding Variants in 2p23.2 and 7p11.2 Associated with Survival of Non–Small Cell Lung Cancer Patients

Zhu, Meng; Geng, Liguo; Shen, Wei; Wang, Yuzhuo; Liu, Jia; Yang, Cheng; Wang, Cheng; Dai, Juncheng; Jin, Guangfu; Hu, Zhibin; Ma, Hongxia; Shen, Hongbing

doi:10.1016/j.jtho.2016.12.025

Cited by 13 publications

(8 citation statements)

References 59 publications

(70 reference statements)

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“…According to the DNB ranking, CCT6A in the CD8 + T cell subpopulation were pre-exhausted biomarkers. CCT6A was strongly correlated with survival of CRC patients, which is consisted with that CCT6A may account for the survival of non-small cell lung cancer (NSCLC) patients ( 25 ). Pre-exhausted T cells emerged as a critical transitional period, wherein the two groups of DNB-neighboring genes flipped their expression patterns.…”

Section: Discussionmentioning

confidence: 83%

Dynamic Network Biomarker of Pre-Exhausted CD8+ T Cells Contributed to T Cell Exhaustion in Colorectal Cancer

Han

Zhong

et al. 2021

Front. Immunol.

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Immunotherapy has achieved positive clinical responses in various cancers. However, in advanced colorectal cancer (CRC), immunotherapy is challenging because of the deterioration of T-cell exhaustion, the mechanism of which is still unclear. In this study, we depicted CD8+ T-cell developmental trajectories and characterized the pre-exhausted T cells isolated from CRC patients in the scRNA-seq data set using a dynamic network biomarker (DNB). Moreover, CCT6A identified by DNB was a biomarker for pre-exhausted T-cell subpopulation in CRC. Besides, TUBA1B expression was triggered by CCT6A as DNB core genes contributing to CD8+ T cell exhaustion, indicating that core genes serve as biomarkers in pre-exhausted T cells. Remarkably, both TUBA1B and CCT6A expressions were significantly associated with the overall survival of COAD patients in the TCGA database (p = 0.0082 and p = 0.026, respectively). We also observed that cellular communication between terminally differentiated exhausted T cells and pre-exhausted T cells contributes to exhaustion. These findings provide new insights into the mechanism of T-cell exhaustion and provide clue for targeted immunotherapy in CRC.

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Section: Discussionmentioning

confidence: 83%

Dynamic Network Biomarker of Pre-Exhausted CD8+ T Cells Contributed to T Cell Exhaustion in Colorectal Cancer

Han

Zhong

et al. 2021

Front. Immunol.

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“…In brief, these studies imply that CCT6A may be involved in disease initiation and progression in patients with specific cancers. For lung cancer, there is only one investigation shows the correlation of CCT6A with worse survival in NSCLC patients (which is only supported by gene expression analysis in TCGA) [16,19]. All these data reveal that CCT6A may As a result, we found that CCT6A expression was overexpressed in tumor tissue compared with adjacent tissue, and ROC curve showed that CCT6A could distinguish tumor tissue from adjacent tissue (despite some patients presented with CCT6A expression in adjacent tissue, it did not affect the predictive power of CCT6A).…”

Section: Discussionmentioning

confidence: 99%

“…CCT6B, as a molecular chaperone involved in protein folding mediated by cytoplasmic chaperonin containing TCP-1, is currently found to be highly expressed in the testis and mucosal wounds [14,15]. As to CCT6A, a few recent data reveal that CCT6A promotes cell proliferation and metastasis in various cancers (such as NSCLC, colon carcinoma, and hepatocellular carcinoma (HCC)) [11,[16][17][18][19][20]. Besides, several clinical practices illuminate that CCT6A correlates with deteriorated tumor features and unsatisfactory prognosis in patients with several cancers (including breast cancer, HCC, and colorectal cancer).…”

Section: Introductionmentioning

confidence: 99%

“…Besides, several clinical practices illuminate that CCT6A correlates with deteriorated tumor features and unsatisfactory prognosis in patients with several cancers (including breast cancer, HCC, and colorectal cancer). As for NSCLC patients, limited evidence is found, just two related existing studies: one literature shows that CCT6A is related to worse survival of NSCLC patients, but that previous finding is only supported by gene expression analysis in The Cancer Genome Atlas (TCGA) [19]; and another study suggests that CCT6A expression levels positively correlate with metastasis in patients with high TGF-β expression, while their findings are based on data collected from MSKCC NSCLC data sets [16].…”

Section: Introductionmentioning

confidence: 99%

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Chaperonin containing t-complex polypeptide 1 subunit 6A correlates with lymph node metastasis, abnormal carcinoembryonic antigen and poor survival profiles in non-small cell lung carcinoma

et al. 2020

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Background: This study aimed to investigate the correlation of chaperonin containing t-complex polypeptide 1 subunit 6A (CCT6A) expression with clinicopathological features and survival profiles in non-small cell lung carcinoma (NSCLC) patients. Methods: A total of 381 NSCLC patients with Tumor, Node, Metastasis (TNM) stage I-IIIA who underwent tumor resection were retrospectively screened. Immunohistochemistry staining and semi-quantitative scoring were used to evaluate CCT6A expression in tumor and adjacent tissues. Clinicopathological features were retrieved. Diseasefree survival (DFS) and overall survival (OS) were calculated. Results: CCT6A expression was elevated in tumor tissue (CCT6A high 47.5% vs. low 52.5%) compared with adjacent tissue (CCT6A high 30.4% vs. low 69.6%) (P < 0.001), and ROC curve displayed that CCT6A could distinguish tumor tissue from adjacent tissue. Moreover, tumor CCT6A high expression was associated with lymph node metastasis (P = 0.001), elevated TNM stage (P = 0.002), and abnormal carcinoembryonic antigen (P = 0.022). Kaplan-Meier curves displayed that tumor CCT6A high expression was negatively correlated with DFS and OS (all P < 0.001). Cox's regression analysis disclosed that tumor CCT6A high expression independently predicted worse DFS (P < 0.001) (hazard ratio (HR) 1.659 (95% confidence interval (CI) 1.318-2.089)), and OS (P < 0.001) (HR 1.779 (95%CI 1.378-2.298)). Conclusions: CCT6A may present some clinical value in the management of NSCLC.

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“…As early as 2006, CCT6A was shown to play an important regulatory role in cancer [19] . Meng Zhu in 2017 found that low-frequency missense variants in the chaperone protein accompanying CCT6A were signi cantly associated with survival in patients with non-small cell lung cancer [20] . Klimczak M used the TCGA database to identify the overexpression of CCT6A in breast cancer as a signi cant contributor to poor prognosis [21] .…”

Section: Discussionmentioning

confidence: 99%

CCT6A, a novel prognostic biomarker for Ewing's sarcoma

Jiang

et al. 2020

Preprint

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Background Ewing's sarcoma (ES) is the second most prevalent malignancy among bone tissue tumors, and there is no adequate prognosis biomarker. The protein encoded by CCT6A is a molecular chaperone. Early studies have suggested that CCT6A is involved in the development of many cancers, however, there is no clear evidence of a role for CCT6A in ES. Methods In this study, we performed a bioinformatics analysis of 32 Ewing sarcoma specimens from the GSE17618 dataset for differences in gene expression and overall survival, event-free survival, and gene expression in different subgroups. Results After three screenings, we identified CCT6A as highly correlated with Ewing's sarcoma prognosis. Survival analysis showed low overall survival (OS) for CCT6A high expression (P = 0.024). On the other hand, Cox regression analysis showed that CCT6A expression, event-free survival (EFS), and age were strongly associated with the prognosis of Ewing sarcoma, identified as independent poor prognostic biomarkers. (CCT6A: P = 0.015; Age: P-value = 0.026; EFS: P-value = 0.001). Conclusion The expression level of CCT6A is strongly associated with the prognosis of Ewing's sarcoma. High expression of the CCT6A gene may serve as a biomarker for poor prognosis in patients with Ewing's sarcoma.

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Exome-Wide Association Study Identifies Low-Frequency Coding Variants in 2p23.2 and 7p11.2 Associated with Survival of Non–Small Cell Lung Cancer Patients

Abstract: These results provided more evidence for the important role of low-frequency or rare variants in the survival of patients with NSCLC.

Cited by 13 publications

References 59 publications

Dynamic Network Biomarker of Pre-Exhausted CD8+ T Cells Contributed to T Cell Exhaustion in Colorectal Cancer

Dynamic Network Biomarker of Pre-Exhausted CD8+ T Cells Contributed to T Cell Exhaustion in Colorectal Cancer

Chaperonin containing t-complex polypeptide 1 subunit 6A correlates with lymph node metastasis, abnormal carcinoembryonic antigen and poor survival profiles in non-small cell lung carcinoma

CCT6A, a novel prognostic biomarker for Ewing's sarcoma

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