scholarly journals Comprehensive Analysis and Validation of Solute Carrier Family 25 (SLC25) in Pan-Cancer

Author(s):  
Ao-ran Liu ◽  
Ying-nan Liu ◽  
Shi-xuan Shen ◽  
Li-rong Yan ◽  
Zhi Lv ◽  
...  

Abstract BackgroundAs the largest gene family functioning in protein transport among human solute carriers, the SLC25 family (mitochondrial carrier family) has been reported to be associated with the genesis and development of many diseases. However, acomprehensiveexplorationfor the roles of SLC family in cancer remains lacking. MethodIn the present study, a total of 15 functional SLC25 family genes were retrieved from all current publications. And multi-dimensional analyses were systematically performed based on the transcriptome and genome data of SLC25 family from a variety of online databases for their expression, mutation and copy number variation, cancer prognosis, signaling pathways and immune cell infiltration. Validation by qPCR was further conducted for the expression of partial SLC25 family members in some tumor tissue.ResultsWe found that SLC25A7 was highly expressed in stomach adenocarcinoma, kidney chromophobeand colon adenocarcinoma, while low expressed in lung adenocarcinoma, thyroid carcinomaas well as head and neck squamous cell carcinoma. SLC25A23 was decreased in colon adenocarcinoma andhead and neck squamous cell carcinoma. SLC25A4 was down-regulated instomach adenocarcinoma,colon adenocarcinoma, kidney renal clear cell carcinoma and head and neck squamous cell carcinoma. Validation results of stomach adenocarcinoma and colon adenocarcinoma were consistent with our bioinformatic prediction. The analysis in regard to cancer-related pathways indicated that SLC25A5 was more likely to be positively associated with carcinogenic pathways such as PI3K-AKT-MTOR, MYC-TARGETS-V2 and E2F-TARGETS. Immune cells including Macrophages M2 and B cells naïve had significant association with SLC25s expression. Survival analysis demonstrated that SLC25A8 was linked to a high-risk effect on the prognosis of cervical squamous cell carcinoma and adenocarcinoma significantly. The majority of SLC25 genes showed high mutation frequency in uterine corpus endometrial carcinoma withan overall average mutation rateof 0.100189. SLC25A8 had extensive copy number variation in different cancer tissue. And SLC25A25 showed high mutation frequency in breast cancer cell lines. As forthe influence of mutation on gene expression and cancer prognosis, SLC25A4 mutation could alter its expression in uterine corpus endometrial carcinoma. Most SLC25 gene mutationmadeprominent effects on the prognosis of patients with uterine corpus endometrial carcinoma. ConclusionAll these findings suggested that the SLC25 family might be crucial to the occurrence, progression and prognosis of tumor. They had the potential to be predictive biomarkers for early diagnosis and prognosis as well as novel targets for individualized treatment of cancer.

2021 ◽  
Author(s):  
Julian Khaymovich ◽  
Andrew Ko ◽  
Amanda Wong ◽  
Daniel Zhu ◽  
Christian Gigante ◽  
...  

Purpose: Inflammatory markers, such as Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR), have been shown to hold significant prognostic value in the context of head and neck cancer (HNC). Recently, delta inflammatory markers, the difference between pre and post- treatment inflammatory marker ratios, have been suggested as potentially significant values in predicting cancer prognosis. Our objective was to evaluate the prognostic utility of delta LMR, NLR, and PLR in head and neck squamous cell carcinoma (HNSCC). Methods: Retrospective cohort study in a tertiary academic hospital setting. Patients diagnosed with HNSCC in the oral cavity, larynx, and oropharynx treated with curative intent treatment were included. The variables collected were age, sex, BMI, alcohol/tobacco exposure, performance scores, ACE-27, tumor characteristics, adjuvant treatment, ECOG score, and lab values. Overall Survival (OS) and Event-Free Survival (EFS) were chosen as endpoints. OS was defined as time from date of treatment to date of last follow-up or death from any cause, and EFS was defined as the start of treatment to any progression, recurrence, or death from any cause. Univariate and multivariate analyses were performed on the primary endpoints. Results: A total of 89 patients were included from 2010 to 2017. In multivariate analysis, EFS was found to be significantly associated with an N stage of 3 (p=0.0005) and delta LMR > -1.48 (p=0.0241). No significant relationships were uncovered with OS in multivariate analysis. Conclusion: A higher delta LMR value (>-1.48) was associated with poorer EFS, but was not associated with OS.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ruoyan Cao ◽  
Suyang Liu ◽  
Jiayu Zhang ◽  
Xianyue Ren ◽  
Xijuan Chen ◽  
...  

TP53INP2 plays an important role in regulating gene transcription and starvation-induced autophagy, however, its function in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, we assessed the expression and prognostic value of TP53INP2. In addition, RNAseq, miRNAseq, copy number variation, and mutation profiles from The Cancer Genome Atlas (TCGA) dataset were applied to evaluate the distinctive genomic patterns related to TP53INP2 expression. We found that TP53INP2 expression was lower in HNSCC compared with normal controls. Patients with higher TP53INP2 expression had longer survival time. Knockdown of TP53INP2 promoted cell viability. Functional analysis exhibited that TP53INP2 was linked to DNA replication, DNA repair, cell cycle, and multiple metabolic pathways. Moreover, TP53INP2 might affect the expression of multiple genes via enhancing the transcriptional activity of nuclear hormone receptors. A competing endogenous RNA (ceRNA) network consisting of 33 lncRNAs, eight miRNAs, and 13 mRNAs was constructed based on the expression of TP53INP2. Taken together, our study highlights the potential value of TP53INP2 in predicting the survival of HNSCC and its important role in the genesis and development of HNSCC.


2021 ◽  
Vol 20 ◽  
pp. 153303382098008
Author(s):  
Hongpan Zhang ◽  
Zhihao Yang ◽  
Guobo Du ◽  
Lu Cao ◽  
BangXian Tan

Growing evidence has suggested that CD155 participates in the regulation of many biological processes ranging cell growth, invasion, and migration from regulation of immune responses in most malignances. However, the impact of prognostic value and CD115-related immune response on the survival in multiple cancers remains incompletely clear. In our study, we assessed the prognostic significance and immune-associated mechanism of CD155 based on data from multiple databases and methods, including UCSC Xena, Oncomine, PrognoScan. We identified that CD155 was commonly upregulated in most human cancers, and High expression of CD155 was closely correlated with unfavorable clinical outcomes in 10/33 of human cancers, while CD155 at low level was responsible for better survival in KICH and PAAD. More intriguingly, CD155 expression had a significant interaction with immune function in several tumors by analyzing Tumor mutational burden and microsatellite in stability, immune score and stromal score. The correlation between immune infiltration and CD155 expression also indicated that CD155 expression positively correlated with CD4+ T cells in Head and Neck squamous cell carcinoma, Lung adenocarcinoma and Colon adenocarcinoma, while had inversely interaction with CD8+ T in Kidney renal clear cell carcinoma and Head and Neck squamous cell carcinoma as well as Tregs in Skin Cutaneous Melanoma, Head and Neck squamous cell carcinoma and Bladder Urothelial Carcinoma. These findings indicate CD155 correlates with cancer immunotherapy function. In conclusions, our observations revealed CD155 might function as immune-associated system in the development of human cancers, and acted as a promising prognostic and therapeutic target against human cancers.


2016 ◽  
Vol 46 (1) ◽  
pp. 53
Author(s):  
Azwar Azwar ◽  
Sofia Mubarika ◽  
Agus Surono

Latar belakang: Karsinoma sel skuamosa kepala dan leher merupakan salah satu kanker terseringdi seluruh dunia. Pendekatan pengobatan agresif dan multidisiplin telah dilakukan, namun belum adapeningkatan yang signifikan dalam kelangsungan hidup 5 tahun, selama 20 tahun terakhir. Kegagalanpengobatan terjadi dalam bentuk kekambuhan lokoregional, metastasis jauh, dan/atau tumor primer kedua.Berbagai penanda molekular tumor telah diteliti untuk mengetahui potensinya dalam memprediksi hasilpenyakit atau respon terhadap terapi.Tujuan: Mengetahui hubungan ekspresi protein p53, Bcl-2, c-Myc,dan MMP-9 berdasarkan gambaran klinikopatologis karsinoma sel skuamosa kepala dan leher di RumahSakit dr. Zainoel Abidin.Metode: Studi menggunakan desain cross sectional. Sampel terdiri dari 60blok parafin karsinoma sel skuamosa kepala dan leher. Prosedur pewarnaan imunohistokimia dilakukandengan menggunakan antibodi monoklonal terhadap p53, Bcl-2, c-Myc, dan MMP-9. Ekspresi proteinp53, Bcl-2, c-Myc, dan MMP-9 dianalisis secara imunohistokimia pada karsinoma sel skuamosa kepaladan leher kemudian hasilnya dihubungkan dengan parameter klinikopatologis seperti usia, jenis kelamin,lokasi tumor, diferensiasi tumor, metastasis kelenjar getah bening dan stadium tumor, kemudian dianalisisstatistik dengan Chi square.Hasil: Hasil penelitian menunjukkan terdapat hubungan bermakna tingkatekspresi p53 dengan metastasis lokal (p=0,021) dan ada hubungan bermakna tingkat ekspresi MMP-9dengan lokasi tumor (p=0,026). Tidak terdapat hubungan ekspresi p53, Bcl-2, cMyc, dan MMP-9 terhadapusia, jenis kelamin, stadium tumor, diferensiasi histologi, tingkat T, N, dan metastasis jauh.Kesimpulan:Ada hubungan ekpresi p53 dengan metastasis kelenjar limfe regional dan ekspresi MMP-9 dengan lokasitumor pada karsinoma sel skuamosa kepala dan leher. Kata kunci: Karsinoma sel skuamosa kepala dan leher, p53, Bcl-2, c-Myc, MMP-9 ABSTRACTBackground: Head and neck squamous cell carcinoma (HNSCC) is one of the most commoncancers world wide. Although aggressive and multidisciplinary approach to the treatment has been done,there is no significant improvement in 5-year survival in the last 20 years. Treatment failure occurredin the form of locoregional recurrence, distant metastasis, and/or a second primary tumor. A variety oftumor molecular markers have been studied to determine their potential in predicting disease outcome orresponse to the therapy. Purpose: To investigate correlation p53, Bcl-2, c-Myc, and MMP-9 expressionto clinicopathologic parameter in head and neck squamous cell carcinoma patient in dr. Zainoel Abidinhospital. Methods: Cross sectional design study. The sample was consisted of 60 paraffin blocks ofhead and neck squamous cell carcinoma. Procedure of immunohistochemical staining used monoclonalantibodies against p53, Bcl-2, c-Myc, and MMP-9. Expression of p53 protein, Bcl-2, c-Myc, and MMP-9were analyzed by immunohistochemistry in head and neck squamous cell carcinoma. Then, the results were linked to clinicopathologic parameters such as age, sex, tumor location, tumor differentiation,lymph node metastasis and tumor stage, and statistically analyzed with Chi square. Results: The resultsshowed there were significant correlation between p53 expression level with local metastasis (p=0,021)and significant correlation of MMP-9 expression levels with tumor location (p=0,026). There were norelationship of p53, Bcl-2, cMyc and MMP-9 expressions based on age, sex, stage tumor, histologicdifferentiation, level of T, N, and distant metastases. Conclusion: There were relationships between p53expression with local metastasis and MMP-9 expression with tumor location in head and neck squamouscell carcinoma. Keywords: Head and neck squamous cell carcinoma, p53, Bcl-2, c-Myc, MMP-9


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