Differential Expression Pattern of THBS1 and THBS2 in Lung Cancer: Clinical Outcome and a Systematic-Analysis of Microarray Databases

Abstract

Thrombospondin 1 and thrombospondin 2 (THBS1 and THBS2) share similar multifunctional domains, and are known to be antiangiogenic. However, the expression pattern of THBS1 and THBS2 is different, and the specific role of THBS2 in different subtypes of lung cancer remains largely unclear. To evaluate the significance of THBS1 and THBS2 in the development of lung cancer, the present study performed a microarray-based systematic-analysis to determine the transcript levels of thrombospondins and their relation to the prognosis in lung cancer. THBS1 was in general underexpressed in lung cancer; in contrast, mRNA levels of THBS2 were markedly overexpressed in a number of datasets of non-small cell lung carcinoma (NSCLC), including lung adenocarcinoma (AC) and squamous cell carcinoma. Similar expression pattern of THBS1 and THBS2 was verified in pulmonary AC cell lines with real-time PCR analysis. The survival of lung AC patients with high THBS2 mRNA expression levels was poorer than patients with low levels of expression of THBS2. In a microarray-based analysis, genes coexpressed with THBS1 or THBS2 were determined. Pulmonary AC patients with a high expression level of sevenTSHB1-coexpressed genes (CCL5, CDH11, FYB, GZMK, LA-DQA1, PDE4DIP, and SELL) had better survival rates than those with a low expression level. Patients with a high expression of seven TSHB2-coexpressed genes (CHI3L1, COL5A2, COL11A1, FAP, MXRA5, THY1, and VCAN) had poor survival rates. Downregulation of VCAN and THBS2 with shRNA inhibited the cell proliferation in the A549 cell line. In summary, THBS1 functions as a tumor suppressor in lung adenocarcinoma. However, THBS2 may play a double-edged role in the progression of lung AC, i.e. anti-angiogenic and oncogenic function. Further study on the mechanism underlying the activity of THBS2 is warranted to have further implications for cancer diagnosis and treatment of pulmonary AC.

Identification of gene modules associated with survival of diffuse large B-cell lymphoma treated with CHOP-based chemotherapy

“…Several researches have demonstrated the positive association between FYB and T-cell activation [42,43]. Favourable prognoses have also been found with the elevated expression of GZMK and FYB in lung cancer [44]. DLBCL studies indicated that higher expression of both FN1 and SPARC correlated with longer survival [45,46].…”

Differential clinical significance of COL5A1 and COL5A2 in tongue squamous cell carcinoma

“…On the other hand, COL5A2 gene expression was also increased in several cancers such as breast cancer and colon carcinoma . Moreover, higher COL5A2 expression was associated with poor clinical outcomes in adenomas and poor survival in lung cancer . Moreover, COL5A2 expression is regulated through PBX1 (pre‐B‐cell leukemia homeobox 1) and HOXB1 (homeobox B1) transcription factors for focal adhesion of endometrial cancer and through MYBL2 transcription factor for susceptibility and clinical outcome of breast cancer .…”

“…Moreover, higher COL5A2 expression was associated with poor clinical outcomes in adenomas 23 and poor survival in lung cancer. 24 Moreover, COL5A2 expression is regulated through PBX1 (pre-Bcell leukemia homeobox 1) and HOXB1 (homeobox B1) transcription factors for focal adhesion of endometrial cancer 25 and through MYBL2 transcription factor for susceptibility and clinical outcome of breast cancer. 26 However, COL5A2 expression was not significantly increased in TSCC and higher COL5A2 expression was associated with better DFS in our TSCC patients, indicating that COL5A2 plays a variety of roles in different cancers.…”

Polyhexamethylene Guanidine-induced Lung Injuries and Tumorigenesis in a Rat Model: Radiologic Evaluation With Pathologic Correlation and RNA Sequencing

“…Additional le 6 summarizes these 96 signi cantly upregulated or downregulated genes. Among the PHMG-regulated genes, CXCR1, AQP3, ROR2, IQGAP3, SUV39H2, and THBS2 are upregulated [10][11][12][13][14][15], and RSPO1, WNT2B, CALML3, GATA4, CES1C, BMP7, SPRY2, and TNFRSF25 are downregulated [16][17][18][19][20], which are associated with lung cancer. In addition, there were some upregulated genes which have been implicated in mediating pulmonary disorders, such as ALOX15, which induces acute lung injury [21], and PDE1A, CHI3L1, and BPIFB1, which play a critical role in pulmonary brosis [22][23][24].…”