Tumor-associated collagen signature in relation to metastasis in lung adenocarcinoma

Journal article

Michael H. Udin, Sarmila Nepali, S. Sonkawade, Scott T. Doyle, Ciprian N Ionita, Yongdong Ouyang, Umesh C. Sharma, Saraswati Pokharel
Journal of Thoracic Disease, 2026

Semantic Scholar DOI PubMedCentral PubMed

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APA Click to copy
Udin, M. H., Nepali, S., Sonkawade, S., Doyle, S. T., Ionita, C. N., Ouyang, Y., … Pokharel, S. (2026). Tumor-associated collagen signature in relation to metastasis in lung adenocarcinoma. Journal of Thoracic Disease.

Chicago/Turabian Click to copy
Udin, Michael H., Sarmila Nepali, S. Sonkawade, Scott T. Doyle, Ciprian N Ionita, Yongdong Ouyang, Umesh C. Sharma, and Saraswati Pokharel. “Tumor-Associated Collagen Signature in Relation to Metastasis in Lung Adenocarcinoma.” Journal of Thoracic Disease (2026).

MLA Click to copy
Udin, Michael H., et al. “Tumor-Associated Collagen Signature in Relation to Metastasis in Lung Adenocarcinoma.” Journal of Thoracic Disease, 2026.

BibTeX Click to copy

@article{michael2026a,
  title = {Tumor-associated collagen signature in relation to metastasis in lung adenocarcinoma},
  year = {2026},
  journal = {Journal of Thoracic Disease},
  author = {Udin, Michael H. and Nepali, Sarmila and Sonkawade, S. and Doyle, Scott T. and Ionita, Ciprian N and Ouyang, Yongdong and Sharma, Umesh C. and Pokharel, Saraswati}
}

Abstract

Background In lung adenocarcinoma (LUAD), a subset of tumors metastasizes to lymph nodes while others do not, despite having a similar tumor stage (T stage). The tumor extracellular matrix (ECM), particularly collagen and elastin, may play a critical role in this variability. This study aimed to determine whether differences in collagen architecture and elastin content within the tumor ECM are associated with susceptibility to nodal metastasis in LUAD. Methods LUAD tissue samples were obtained from 120 patients (54 metastatic and 66 non-metastatic) diagnosed between 2005 and 2022 at Roswell Park Comprehensive Cancer Center. Sections were stained with Masson’s trichrome and Elastica Van Gieson on separate slide replicates. Collagen and elastin volume fractions were quantified using Aperio ImageScope. Collagen fiber alignment was assessed using second harmonic generation (SHG) imaging and analyzed with CurveAlign software. Results Metastatic tumors demonstrated significantly higher unidirectional alignment of collagen fibers compared to the crisscross pattern seen in non-metastatic tumors (0.87 vs. 0.78, P=0.003). Elastin volume fraction was significantly lower in metastatic tumors (0.29 vs. 0.38, P=0.001), while total collagen content did not differ significantly (P=0.87). The elastin-to-collagen ratio was significantly reduced in metastatic tumors (P=0.002), indicating a shift in ECM composition rather than an absolute increase in collagen. Conclusions Decreased elastin content and increased collagen fiber alignment are associated with nodal metastasis in LUAD and may reflect alterations in stromal organization and stiffness that promote tumor dissemination. These ECM features may serve as potential biomarkers for identifying LUAD patients at higher risk for nodal metastasis. Further large-scale studies are needed for validation.