Researchers discover correlation between tumour shrinkage and protein expressed in bones

A team of researchers have identified a method to measure results of a rectal cancer treatment by quantifying the levels of a certain protein marker, reported lead author Mirna Primasari from Dr Cipto Mangunkusumo General Hospitalai??i??s Radiotherapy Department in Jakarta, Indonesia

Their study was published in the peer-reviewed open access journal Advances in Modern Oncology Research.


Osteopontin protein in lung from patient with IPF (Idiopathic Pulmonary Fibrosis)

Patients of locally advanced rectal carcinoma typically undergo evidence-based treatments such as neoadjuvant chemoradiation (CRT) which combines adjusted low dose chemotherapy and radiation therapy done before surgery. It is proven to be more effective compared to adjuvant CRT which is done after surgery, according to the Indonesian researchers.

In addition, the latest National Comprehensive Cancer Network (NCCN) guidelines also accepted neoadjuvant CRT as the standard therapy for locally advanced rectal cancer.

ai???It provides better result in local control and minimizing treatment toxicity. It is also associated with tumor downstaging, increased tumor resectability, significantly higher rate of pathologic complete response, less advanced primary tumor and regional lymph nodes stage, and fewer cases with venous, perineural or lymphatic invasion,ai??? Primasariai??i??s team said of neoadjuvant CRT.


However, its treatment response varies between different locally advanced rectal cases due to many factors, including tissue hypoxia ai??i?? i.e. depletion of oxygen ai??i?? which decreases chemotherapy and radiation sensitivity.

Osteopontin, a multifunctional protein usually highly expressed in bones but also expressed by various cell types, is an emerging endogen hypoxic marker (or measure of oxygen deprivation to indicate cancer aggressiveness) due to its ai???significant correlation towards tumor partial oxygen pressure (pO2), also a more accurate chronic hypoxic marker,ai??? according to the researchers.

OPN level, which is overexpressed in tumours, has been shown to increase in several carcinomas such as lung, breast, gastrointestinal, ovarium, prostate, pancreas, colon and rectal cancers. ai???In cervical carcinomas, the OPNs level elevates 90 times compared to normal tissue. In breast cancer, high level of OPN correlates with bad prognosis. It also correlates with prostate cancer recurrence in 72 months,ai??? noted the team.


Location and appearance of two example colorectal tumors ai??i?? Blausen Medical Communications, Inc.

Yet, according to Primasari and her colleagues, ai???As far as we know, there is no research that measured OPN quantity in rectal cancer tissue and correlated it with tumor shrinkage response in neoadjuvant

Between January 2012 and January 2015, Primasariai??i??s team screened 14 patients with locally advanced rectal cancer who received neoadjuvant CRT at the Radiotherapy Department of Dr. Cipto Mangunkusumo General Hospital, and measured the patientsai??i?? tumor shrinkage percentage and corresponding OPN level.

Using the enzyme-linked immunosorbent assay (ELISA) method, the researchers found that OPN level quantitative results showed a significant strong negative correlation between the OPN level and tumor shrinkage.

The study proved that OPN, which characterizes hypoxia, is a bad prognostic towards tumor shrinkage in neoadjuvant CRT. ai???Hypoxic condition increases stimulated secretion of OPN in vitro,ai??? according to their report, and since it has been proven from previous research that the plasma OPN level is inversely correlated with the tissueai??i??s partial oxygen pressure, ai???OPN level will get higher along with worsening hypoxic condition,ai??? they added.


Micrograph of a tubular adenoma (left of image), a type of colonic polyp and a precursor of colorectal cancer. Normal colorectal mucosa is seen on the right of the image. H&E stain.

ai???Therefore quantitative measurement of OPN could be used as one of the examinations to identify which patients would need and benefit from ai???hypoxia-targeted therapyai??i?? in order to increase the clinical outcome,ai??? the researchers noted.

In addition, OPN cut-off value could also forecast non-responsiveness of tumor shrinkage in neoadjuvant CRT with 100% sensitivity and 81.8% specificity, the Indonesian team found. ai???The cut-off value of 0.538 ng/mL could predict the non-responsiveness of tumor shrinkage,ai??? Primasari and her colleagues reported, but cautioned that further study and analysis with larger sample is required.

Due to no previous research which involves the OPN protein quantitative value from rectal cancer tissue or rectal normal tissue, ai???We have not been able to calculate the increase of OPN values in rectal carcinoma since there was no data for normal rectal tissue OPN quantitative values,ai??? Primasariai??i??s team observed, adding that more research will be needed.

ai???It would also be very interesting to do a prospective study for the next research to get more data for analysis, for example correlation of serum OPN with tumor OPN and tumor percentage shrinkage, OPN levels before and after therapy, etc.,ai??? their report concluded.

The research paper is available online at