Tumor-Associated Collagen Signature Helps Predict Gastric Cancer Prognosis

By Lorraine L. Janeczko

December 17, 2021

NEW YORK (Reuters Health) - The level of tumor-associated collagen signature of gastric cancer (TACSGC) may help predict which patients are likely to benefit from adjuvant chemotherapy, research from China suggests.

"This study showed two key findings: 1) patients with resected stage-II-III gastric cancer having a higher TACSGC level (had) worse survival, and 2) those with a lower TACSGC level had better responses to adjuvant chemotherapy," said Dr. Jun Gong, a medical oncologist in the Gastrointestinal Disease Research Group at Cedars-Sinai Cancer, in Los Angeles, who was not involved in the study.

"This study's importance is the unique ability to predict who with gastric cancer may benefit from adjuvant chemotherapy. Currently, no such test really exists," Dr. Gong told Reuters Health by email. "There has not been an established biomarker in gastric cancer that incorporates features of the tumor microenvironment, in this instance the main component of extracellular matrix (collagen)."

As described in JAMA Network Open, Dr. Jun Yan of Southern Medical University in Guangzhou and colleagues conducted a retrospective study involving two groups of consecutive patients with gastric cancer: a training cohort of 294 patients treated over two years at one hospital, and a validation cohort of 225 patients treated over fourteen months at a different hospital. The median age of all study participants was 57 years, and almost 70% were male.

The researchers characterized TACSGC through multiphoton imaging by laser scanning multiphoton microscopy. They determined 146 collagen features in the tumor microenvironment, including morphologic, histogram-based, gray-level concurrence matrix-based, and Gabor wavelet transform.

A higher TACSGC level was significantly linked with worse disease-free survival (DFS) and overall survival (OS) in both the training group (DFS: hazard ratio, 3.57; OS: HR, 3.54) and the validation group (DFS: HR, 3.10; OS: HR, 3.24).

Patients with stage-II/III gastric cancer and low TACSGC levels responded better to adjuvant chemotherapy than those with high TACSGC levels (DFS: HR, 0.65; P=0.03; OS: HR, 0.55; P=0.004; P<0.001 for interaction for both comparisons).

The authors caution that the study is limited by its retrospective design and recommend a prospective, multicenter trial to validate the performance of TACSGC.

Dr. Yanghee Woo, an associate professor of surgical oncology and the director of the Gastroenterology Minimally Invasive Therapy Program at City of Hope Comprehensive Cancer Center in Duarte, California, called this an "innovative and clinically impactful study."

"The authors present both a novel TACSGC signature and a clinically applicable multiphoton imaging technique that provides prognostic information," Dr. Woo told Reuters Health by email. "The main significant aspects of this study are that TACSGC was developed and validated with a large training cohort with an almost equal percentage of intestinal and diffuse subtypes."

"This study has the potential to guide future studies investigating the impact of the structural tumor microenvironment on patient outcomes," she added. "Moreover, it may assist in guiding a multidisciplinary treatment strategy by providing additional prognostic information to help determine the benefit of adding adjuvant chemotherapy for patients with stage-II and -III gastric cancer after radical resection."

"Because collagen provides the main function of the extracellular matrix, and increased collagen density enhances the invasiveness of tumor cells by inducing hypoxia and impeding anticancer drug delivery, it is not surprising that a highly collagen-dense tumor microenvironment would be a negative prognostic indicator in solid tumors," Dr. Woo explained. "What is fascinating is that a unique multiple collagen feature-based signature can easily be imaged. I commend the authors for their discovery of TACSGC and the method for assessing the structural tumor microenvironment in gastric cancer."

In a linked editorial, Drs. Jesse A. Berlin and Daniel V. Catenacci, editors of JAMA Network Open, write, "Chen and colleagues have done an excellent job of showing that TACS may be a useful addition in helping understand gastric cancer prognosis."

"Patients with low TACS seem to be more likely to respond to chemotherapy, but this needs further prospective validation in independent data sets," they add.

Dr. Yan and co-author Dr. Shuangmu Zhuo did not respond to requests for comment.

SOURCE: https://bit.ly/322YmHu and https://bit.ly/3s6JjaN JAMA Network Open, online November 30, 2021.

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