Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer

Abstract

Research on molecular mechanisms underlying the carcinogenesis of non-small cell lung cancer (NSCLC) may provide gene targets in critical pathways valuable for improving the efficacy of therapy and survival of patients with NSCLC. However, the molecular markers highly sensitive for the prognosis and treatment evaluation of NSCLC are not yet available. To explore candidates, we conducted an oligonucleotide microarray study with three pairs of NSCLC and normal lung tissue, and determined 8 differentially expressed genes including the Human MutT homologue (hMTH1), Surfactant protein D (SPD), Human hyaluronan binding protein 2 (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit (ITGA11), Collagen type XI alpha I (COL11A1), and Lungspecific X protein (Lun X). Four lung cancer-related markers MUC-1, hTERT, hnRNP B1, and CK-19 were also incorporated for further analysis. The expression profiles of the twelve genes in seventy pairs of NSCLC tumor and normal lung tissue were then detected quantitatively by using membrane array and quantitative real-time PCR (qRT-PCR). The data of the membrane array and qRT-PCR were compared for consistency and the potential of these mRNA markers in clinical application. The results showed that membrane array and qRT-PCR obtained consistent data for the tested genes in both sensitivity and specificity (correlation coefficient 0.921, p<0.0001). For patients' clinicopathological characteristics, the overexpression of hMTH1, SPD, HABP 2, ITGA11, COL11A1, and CK-19 was significantly correlated with the pathological stage (p<0.05). In addition, the overexpression of hMTH1, SPD, ITGA11, and COL11A1 was correlated with lymph node metastasis and poor prognosis. This is the first report relating SPD to a prognosis marker for NSCLC. Moreover, the combined detection of these four mRNA markers by membrane array had a sensitivity of 89% and a specificity of 84% for NSCLC, significantly higher than these markers had achieved separately. In conclusion, we identified mRNA markers for NSCLC prognosis and therapy evaluation from differentially expressed genes determined by using microarray. Further studies are needed to collect the data of the mRNA markers used in clinical practice.

Identification of an intermediate signature that marks the initial phases of the colorectal adenoma-carcinoma transition

“…The importance of collagens was emphasized in a study identifying COL11A1 as a member of a metastasisassociated gene signature in both squamous cell carcinomas and adenocarcinomas of non-small cell lung cancer (46). The overexpression of COL11A1 was also reportedly correlated with lymph node metastasis and poor prognosis of patients with non-small cell lung cancer (47). The overexpression of COL10A1 was recently found in breast cancer (48), indicating the important participation of these particular collagens in tumorigenesis.…”

Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice

“…The FGFR3 and TTYH1 genes are already reported to be associated with bone metastasis in breast cancers (16). TM4SF4 and CRYM genes were reported as tumor markers in lung cancer (17)(18)(19). FOLR1 gene was reported to be overexpressed in lung adenocarcinoma (20,21) and has critical involvement in drug resistance (22).…”

COL11A1 — Genetic Biomarker Targeted in Stool Samples for Early Diagnosis of Colorectal Cancer in Patients at Risk

“…Previous studies have found overexpression of the COL11A1 gene in different types of cancers, such as non-small cell lung (NSCLC), ovarian, oral cavity and colorectal cancers [13][14][15][16]. In particular, overexpression of the COL11A1 gene was found to be correlated with invasion and metastasis of these cancers [13][14][15][16].…”

“…In particular, overexpression of the COL11A1 gene was found to be correlated with invasive and metastatic potential of these cancers [13][14][15][16].…”