Cell-surface marker discovery for lung cancer

Abstract

Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients.

Identifying the Best Marker Combination in CEA, CA125, CY211, NSE, and SCC for Lung Cancer Screening by Combining ROC Curve and Logistic Regression Analyses: Is It Feasible?

“…With accumulating studies, a growing number of lung cancer-associated markers, including DNA, RNA, protein, and cell surface markers, have been found [ 29 – 34 ]. The value of each marker in the screening of lung cancer is different.…”

Bovine herpesvirus 4-based vector delivering the full length xCT DNA efficiently protects mice from mammary cancer metastases by targeting cancer stem cells

“…10 xCT is only expressed by a few normal cell types (astrocytes, microglia and some myeloid cells), 7 while it is overexpressed in numerous cancers, including a high percentage of mammary tumors. [11][12][13][14][15] xCT expression has been observed in the CSCs of several cancer types, such as glioblastoma, colorectal, lung and gastric cancers, 16 where it is stabilized on the cell membrane via interaction with two stem cell markers, Mucin-1 and CD44v. 17 xCT is therefore a promising target for the treatment of many cancers.…”

Proteomic pattern of cervico-vaginal fluid (CVF) in an ovarian cancer diagnosis — pilot study

“…Ly6/PLAUR domain-containing protein3 (LYPD3) has been identified in non-small cell lung cancer, colorectal and breast cancer. It seems to be involved in cell migration, invasion and tumor progression [20][21][22]. LYPD3 protein deserves special attention because it occurred in all the serous OC samples in our study.…”