Determining the presence of a protein in non-tumor\u00a0cells\u00a0within the cancer microenvironment could be one of the keys to\u00a0establishing\u00a0prognosis in patients with colon and rectal cancer. It may also help\u00a0identify\u00a0which patients could\u00a0benefit\u00a0from immunotherapy or from treatments aimed at inhibiting a specific protein linked to\u00a0tumor\u00a0proliferation. This is highlighted by a new study published in the journal Gut, led by a multidisciplinary team of pathologists,\u00a0oncologists\u00a0and biologists from the Hospital del Mar Research Institute (HMRIB), the Institute for Research in Biomedicine (IRB Barcelona), and the CIBER Oncology area (CIBERONC).\u00a0<\/p>\n
These specific cells, which express a particular protein (CTHRC1) and are known as\u00a0CTHRC1(+) CAFs, belong to a population of cancer-associated fibroblasts-connective tissue cells that, in\u00a0tumors, form part of their microenvironment and help them proliferate. To\u00a0determine\u00a0their potential role as a biomarker<\/a>, using immunohistochemistry tests routinely applied in Pathology services for colon and rectal\u00a0tumors, a complex multidisciplinary validation process was\u00a0required.\u00a0<\/p>\n First, the potential of CTHRC1(+) CAFs as predictive markers of treatment response was studied across\u00a017 cohorts\u00a0comprising\u00a0samples from\u00a0nearly 3,000\u00a0patients.\u00a0Next,\u00a0tumor\u00a0cell RNA was\u00a0analysed\u00a0at the single-cell level to\u00a0identify\u00a0the most promising cell populations. Finally, the proteins they expressed were\u00a0determined. At the end of the process, only those cells expressing a specific protein-CTHRC1(+) CAFs-retained\u00a0predictive capacity.\u00a0<\/p>\n The results were\u00a0validated\u00a0using patient samples from individuals who had received different treatments across several national and international hospitals, including the Hospital\u00a0Cl\u00ednico\u00a0Universitario de Valencia, the Hospital Universitario Germans Trias\u00a0i\u00a0Pujol, and Hospital del Mar. In this regard, Dr Alexandre Calon, one of the study’s principal investigators and coordinator of the Translational Research Group in\u00a0tumor\u00a0Microenvironment at the Hospital del Mar Research Institute, highlights that “the validated marker maintains strong predictive and prognostic performance across patient cohorts.”\u00a0<\/p>\n Another key finding is that it may also help\u00a0determine\u00a0patient prognosis. The new marker enables measurement of the activity of a cytokine in the\u00a0tumor\u00a0microenvironment, TGF-beta, which is associated with poorer disease outcomes.\u00a0High levels\u00a0of CTHRC1 protein are linked to treatment resistance. This also suggests a potential therapeutic target in the form of inhibitors of this protein, which should be further investigated.\u00a0“The\u00a0tumor\u00a0microenvironment plays a decisive role in the progression of colorectal cancer and in its response to treatments. Over the years, our research has shown that TGF-beta is a key regulator of this ecosystem, modulating the\u00a0behaviour\u00a0of stromal cells surrounding the\u00a0tumor. The identification of CTHRC1 as a TGF-beta-induced factor exemplifies how basic research can lead to clinically applicable biomarkers,” states Dr Eduard Batlle, ICREA researcher at IRB Barcelona and member of CIBERONC.\u00a0<\/p>\n Determining\u00a0which patients may\u00a0benefit\u00a0from immunotherapy\u00a0<\/p>\n In this same context, the findings may also help advance the use of\u00a0immunotherapy<\/a>\u00a0in patients with colon and rectal cancer. Currently, this approach\u00a0is applicable\u00a0to only\u00a0a very small\u00a0proportion of patients-around 5%-and it is not effective in all cases. The study\u00a0indicates\u00a0that\u00a0the presence of CTHRC1(+) CAFs makes it possible to\u00a0determine\u00a0the state of immune cells within the\u00a0tumor\u00a0and their ability to act against neoplastic cells. Moreover, its usefulness is not limited to patients previously considered eligible for this treatment.\u00a0<\/p>\n “This biomarker improves the selection of patients who could potentially benefit from immunotherapy,”\u00a0explains Dr Clara\u00a0Montagut, also involved in the study and Head of Section of the Medical Oncology Department at Hospital del Mar and researcher at its institute. This, she notes,\u00a0“could help guide therapeutic strategies for patients with colon and rectal cancer.”\u00a0Furthermore, the results could\u00a0be applicable\u00a0to other\u00a0tumor\u00a0types, such as breast and lung cancer.\u00a0<\/p>\n One of the major innovations of the study is that the presence of the validated marker can be\u00a0determined\u00a0using\u00a0immunohistochemistry tests, which are routinely available in any hospital Pathology service. Dr Mar Iglesias, first author of the study, researcher at HMRIB and CIBERONC, and Head of the Pathology Department at Hospital del Mar (part of the\u00a0dibi\u00a0network), explains that\u00a0“the results position CTHRC1(+) CAFs as a useful marker with the potential to be integrated into routine clinical practice in our services and hospitals, thereby helping to guide the selection of the most appropriate treatment for each patient.”\u00a0<\/p>\n Source:<\/p>\n IMIM (Hospital del Mar Medical Research Institute)<\/a><\/p>\n Journal reference:<\/p>\n