Pan-cancer analysis of trophinin-associated protein with potential implications in clinical significance, prognosis, and tumor microenvironment in human cancers.
Pan-cancer analysis of trophinin-associated protein with potential implications in clinical significance, prognosis, and tumor microenvironment in human cancers.
复制标题
肌营养蛋白相关蛋白的泛癌分析对人类癌症的临床意义、预后和肿瘤微环境具有潜在影响
DOI：
10.3389/fonc.2022.971618
复制
发表时间：
2022
影响因子：
4.7
通讯作者：
Peng, Fang
中科院分区：
文献类型：
--
作者：
Li, Zhenfen;Pu, Zhangya;Yang, Ziyue;Zhu, Yuanyuan;Deng, Ying;Li, Ning;Peng, Fang
研究背景Trophin-associated protein（TROAP）是一种细胞质蛋白，在微管骨架组装过程中起重要作用。越来越多的证据表明TROAP在调节细胞增殖和迁移中的重要作用，但尚不清楚它如何促进癌症进展。方法应用GEPIA 2、Cancer Cell Line Encyclopedia、UALCAN、Human Protein Atlas、PrognoScan等网站分析TROAP在各种肿瘤中的表达，并进一步评价其与预后的关系。通过Western blot和实时荧光定量PCR分析，我们验证了TROAP在肝细胞癌（HCC）和结直肠癌（CRC）中的表达水平。选择10对HCC和CRC组织进行免疫组化，以分别确定肿瘤和邻近组织中的TROAP表达水平。TROAP在CRC和HCC细胞中的敲低，以验证其在恶性表型中的作用。使用cBioPortal和SangerBox数据库确定肿瘤中TROAP的基因组和转录后改变。此外，TISIDB用于研究不同癌症类型中TROAP表达与肿瘤微环境（TME）之间的关系。此外，使用GSCALite和CellMiner数据库发现TROAP表达与药物敏感性之间存在相关性。结果TROAP在大多数肿瘤中表达显著上调，这与我们在HCC和CRC细胞中验证的实验结果以及免疫组化结果一致。预后不良与TROAP异常表达有关。我们的研究结果表明TROAP诱导的恶性表型和肿瘤发生可能是由于PI 3 K/Akt/GSK-3β信号通路的激活。此外，我们发现TROAP表达与各种肿瘤的基因组和转录后改变之间存在相关性，包括肿瘤突变负荷和微卫星不稳定性。接下来，我们证明了TROAP表达与免疫细胞（如中性粒细胞和巨噬细胞）的浸润相关，并与TME中的免疫调节相关基因相关。此外，TROAP表达在预测药物敏感性中的潜在作用，包括美法仑和苯丁酸氮芥。结论TROAP的表达与肿瘤的恶性表型、功能机制、生存可能性、TME、治疗潜力及药物敏感性预测等密切相关。因此，TROAP是预测癌症结果的有前途的生物标志物和治疗靶点。
Background Trophinin-associated protein (TROAP), a cytoplasmic protein, is essential for microtubule cytoskeleton assembly. Mounting evidence demonstrates the vital role of TROAP in regulating the proliferation and migration of cells, but it is unclear how it contributes to cancer progression. Methods The online portals of GEPIA2, Cancer Cell Line Encyclopedia, UALCAN, Human Protein Atlas, and PrognoScan were used to analyze TROAP expression in various tumors and further evaluate its correlation with prognosis. With Western blot and quantitative real-time PCR analysis, we validated TROAP expression levels in hepatocellular carcinoma (HCC) and colorectal cancer (CRC). Ten pairs of HCC and CRC tissues were selected for immunohistochemistry to determine TROAP expression levels in tumors and adjacent tissues, respectively. TROAP knockdown in CRC and HCC cells to verify its role in malignant phenotypes. The genomic and post-transcriptional alterations of TROAP in tumors were determined using the cBioPortal and SangerBox databases. Also, TISIDB was used to investigate the relationship between TROAP expression and tumor microenvironment(TME) among different cancer types. Moreover, a correlation was found between the expression of TROAP and drug sensitivity using GSCALite and CellMiner databases. Results TROAP expression was significantly upregulated in most cancer types, which is consistent with our validated experimental results in HCC and CRC cells, and immunohistochemistry results. And a poor prognosis was linked to TROAP aberrant expression. Our findings indicated that malignant phenotypes and tumorigenesis induced by TROAP could be due to an activation of the PI3K/Akt/GSK-3β signaling pathway. Furthermore, we found a correlation between TROAP expression and genomic and post-transcriptional alterations in various tumors, including tumor mutation burden, and microsatellite instability. Next, we demonstrated that TROAP expression was associated with the infiltration of immune cells, such as neutrophils and macrophages, and correlated with immunomodulation-related genes in the TME. Additionally, the potential role of TROAP expression in predicting the sensitivity of drugs, including melphalan and chlorambucil, was demonstrated. Conclusions Collectively, these findings indicated a significant correlation between TROAP expression and malignant phenotype, functional mechanism, survival possibility, TME, therapeutic potential, and prediction of drug sensitivity in various cancers. Hence, TROAP is a promising biomarker and therapeutic target for predicting cancer outcomes.
登录
查看更多内容
影响因子：
64.5
作者：
Litchfield K;Reading JL;Puttick C;Thakkar K;Abbosh C;Bentham R;Watkins TBK;Rosenthal R;Biswas D;Rowan A;Lim E;Al Bakir M;Turati V;Guerra-Assunção JA;Conde L;Furness AJS;Saini SK;Hadrup SR;Herrero J;Lee SH;Van Loo P;Enver T;Larkin J;Hellmann MD;Turajlic S;Quezada SA;McGranahan N;Swanton C
通讯作者：
Swanton C
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.5
作者：
Burger ML;Cruz AM;Crossland GE;Gaglia G;Ritch CC;Blatt SE;Bhutkar A;Canner D;Kienka T;Tavana SZ;Barandiaran AL;Garmilla A;Schenkel JM;Hillman M;de Los Rios Kobara I;Li A;Jaeger AM;Hwang WL;Westcott PMK;Manos MP;Holovatska MM;Hodi FS;Regev A;Santagata S;Jacks T
通讯作者：
Jacks T
影响因子：
--
作者：
Li, Kai;Zhang, Ruo;Zhang, Lei
通讯作者：
Zhang, Lei
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.