Identification of stromal cell-derived factor 4 as a liquid biopsy-based diagnostic marker in solid cancers

Sep 24, 2026

Uploaded by Pentious

Serum diagnostic biomarkers are needed to improve prognosis in solid malignant tumors. A single-institution study evaluated serum stromal cell-derived factor 4 (SDF4) as a liquid biopsy-based diagnostic marker, measuring SDF4 in serum from 582 patients with solid cancers and 80 healthy volunteers, alongside assays in gastric cancer cell lines and immunohistochemistry in tumor tissue. SDF4 levels were higher in all cancer types and, for gastric cancer, distinguished patients from controls with AUC 0.973, sensitivity 89%, and specificity 99%. SDF4 increased in early-stage disease and supported the feasibility of SDF4 as a diagnostic candidate for gastric cancer and other malignancies.

LanguageEnglish

CategoryHealthcare

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Pages9

Reading Time23 min

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Identification of stromal cell-derived factor 4 as a candidate diagnostic biomarker

Serum SDF4 evaluation in cancer patients and healthy volunteers

Selection of SDF4 from secretome and public database analyses

Validation in vitro and in primary gastric cancer tissues

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Identification of stromal cell‑derived factor 4 as a liquid biopsy‑based diagnostic marker in solid cancers Takahiro Shinozuka, Mitsuro Kanda*, Dai Shimizu, Shinichi Umeda, Hideki Takami, Yoshikuni Inokawa, Norifumi Hattori, Masamichi Hayashi, Chie Tanaka, Goro Nakayama & Yasuhiro Kodera There is a need for serum diagnostic biomarkers to improve the prognosis of solid malignant tumors. Here, we conducted a single‑institutional study to evaluate the diagnostic performance of serum stromal cell‑derived factor 4 (SDF4) levels in cancer patients. Serum samples were collected from a total of 582 patients with solid cancers including gastric cancer (GC) and 80 healthy volunteers. SDF4 protein levels in sera, and conditioned media or lysates of human GC cell lines were measured by enzyme‑linked immunosorbent assay, and those in GC tissue by immunohistochemistry. Serum SDF4 levels were higher in patients with cancer than the healthy control in all cancer type. Regarding GC, serum SDF4 levels distinguished healthy controls from GC patients with the area under the curve value of 0.973, sensitivity of 89%, and specificity of 99%. Serum SDF4 levels were significantly elevated inpatient with early stage GC. In immunohistochemistry, the frequency ofSDF4‑positive GC tumors did not vary significantly between GC stages. The ability of human GC cell lines to both produce and secrete SDF4 was confirmed in vitro. In conclusion, serum SDF4 levels could be a promising candidate for a novel diagnostic biomarker for GC and other malignancies. Early detection of cancer is crucial to reducing cancer mortality worldwide. In recent years, various liquid-based materials, including exosomes, circulating tumor DNA, and serum noncoding RNAs, have been developed as diagnostic biomarkers; however, the measurement is generally technically complex and expensive, which hinders their utility in clinical applications1. Thus, there is still a need for identifying accurate serum diagnostic biomarkers that can be routinely and inexpensively measured for large-scale screening of early stage cancer, particularly solid cancers2. Gastrointestinal cancers such as gastric cancer (GC) and colorectal cancer have high mortality rates worldwide3. Endoscopy has been the standard method for screening and diagnosis of gastrointestinal cancers, but it has several drawbacks, such as its invasive nature, risk of complications, time-intensive tissue evaluation, and excessive cost. Serological tumor biomarkers are desirable for cancer screening in terms of the easy and relatively non-invasive method of sample collection and low cost4. However, conventional serum tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are not satisfactory due to their relatively low sensitivity and specificity5,6. In the case of GC, there is a particularly clear need for a serum diagnostic marker that is elevated in patients with early stage GC compared with healthy individuals. We employed a dataset of previously reported secretome analyses using GC cell lines to identify new diagnostic biomarkers that could be secreted to circulation7 and further screened candidate proteins using two public databases, the human cancer secretome database (HCSD) and The Cancer Genome Atlas (TCGA) database8,9. A pilot experiments were performed to measure blood levels of candidate proteins in healthy controls and GC patients, and we found that stromal cell-derived factor 4 (SDF4) had the best diagnostic ability for GC. Therefore, SDF4 was selected as the final candidate for a diagnostic biomarker in this study, as a potential serum diagnostic tumor marker for GC and other cancers (breast cancer, colorectal cancer, pancreatic cancer, esophageal cancer and hepatic cancer) . SDF4 is a 45 kDa Ca2+-binding protein expressed by various normal human tissues, including gastric tissues10, 11. Some studie

FAQs

What diagnostic role does serum SDF4 play in solid cancers?

Serum stromal cell-derived factor 4 (SDF4) levels are higher in patients with solid cancers than in healthy controls, supporting its potential as a serum diagnostic biomarker.

How well does SDF4 distinguish gastric cancer patients from healthy volunteers?

For gastric cancer, serum SDF4 differentiated healthy controls from gastric cancer patients with AUC 0.973, sensitivity 89%, and specificity 99%.

What evidence supports SDF4 as a biomarker candidate beyond serum measurements?

The study confirms that human gastric cancer cell lines can both produce and secrete SDF4 in vitro and examines SDF4 distribution in primary gastric cancer tissues using immunohistochemistry.

Sep 24, 2026

Uploaded by Pentious