β₆‐integrin serves as a novel serum tumor marker for colorectal carcinoma

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer‐related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β6‐integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro‐ and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non‐CRC control patients. A cut‐off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6‐levels were assessed in 26 CRC patients, pre‐ and post‐surgery, as well as during follow‐up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow‐up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.

Identification of a Nine-Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival of Pancreatic Cancer

“…Anti-ITGA5B6 antibody alone or with trastuzumab halted tumor growth (42). ITGB6 was also considered as a novel serum marker and a highly efficient target for immunoliposome-mediated drug delivery in colon cancer (43). ARNTL2 is a transcriptional activator and a core component of the circadian clock.…”

Markers of metastatic colorectal cancer

“…In a study cohort of 269 CRC patients, β6-integrin predicted the onset of metastatic disease. In the same study, the results were prospectively confirmed in 40 CRC patients [12].…”

Silencing of ITGB6 inhibits the progression of cervical carcinoma via regulating JAK/STAT3 signaling pathway

“…It is a liposome drug delivery target and has specific tumor-interrelated properties, making a latent targeting receptor for cancer therapy (7). Recently, many studies have confirmed that integrin αvβ6 or ITGB6 plays an important role in various cancers, including epithelial ovarian cancer, colorectal carcinoma and breast cancer (10,(21)(22)(23). Furthermore, Hazelbag et al reported that αvβ6 overexpression is an unfavorable prognostic factor in CC and can predict the onset of metastatic disease (13).…”

“…Metastasis and invasion are the crucial biological features of malignant tumor and the pathological basis of tumor recurrence and deterioration. One study has reported that in colorectal carcinoma cells, ITGB6 can promote its own expression via autocrine signaling, induce chemotherapy resistance, cell proliferation, migration, and invasion, and inhibit apoptosis with its unique cytoplasmic tail; meanwhile, other integrins have no such effect (21). The anomalous induction of EMT is of vital importance in the metastasis and invasion of tumors.…”