Article Data

  • Views 350
  • Dowloads 128

Original Research

Open Access

COL12A1 as a prognostic biomarker in HER2-enriched breast cancer and its association with immune infiltration

  • Yi Hu1,†
  • Xiaomei Huang2,†
  • Xiaohui Lu1,*,
  • Shan Lin3,*,

1Department of Clinical Laboratory, Xiamen Key Laboratory of Genetic Testing, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 361003 Xiamen, Fujian, China

2Department of Marine Biology, Xiamen Ocean Vocational College, 361100 Xiamen, Fujian, China

3Department of Orthopedics, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 361003 Xiamen, Fujian, China

DOI: 10.22514/ejgo.2022.045 Vol.43,Issue 5,October 2022 pp.85-90

Submitted: 20 June 2022 Accepted: 16 September 2022

Published: 15 October 2022

*Corresponding Author(s): Xiaohui Lu E-mail:
*Corresponding Author(s): Shan Lin E-mail:

† These authors contributed equally.


To inspect the expression, characteristics, clinical prognostic value and the level of immune infiltration of Collagen Type XII Alpha 1 Chain (COL12A1) in breast cancer (BC) using bioinformatics. We investigated the expression of COL12A1 in breast cancer and normal breast tissues using Tumor IMmune Estimation Resource (TIMER2.0) and the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). The correlation between COL12A1 and overall survival (OS) was determined using Kaplan-Meier Plotter in BC. The correlation between COL12A1, immune infiltrating cells and immune checkpoints was detected via TIMER2.0. We found that the expression of COL12A1 was significantly higher in BC tissues than in normal tissues. A higher expression level of COL12A1 correlated with lymph node metastasis and worse OS in human epidermal growth factor receptor 2 (HER2)-enriched BC patients. Moreover, COL12A1 was positively correlated with M2 macrophages and immune checkpoint programmed cell death 1 ligand 2 (PDCD1LG2) but negatively correlated with activated natural killer (NK) cells and cluster of differentiation 8 (CD8)+ T cells in HER2-positive BC. COL12A1 might act as a biomarker indicating poor prognosis in HER2-enriched BC and correlate with immune infiltration in HER2-positive BC.


COL12A1; Breast cancer; Immune infiltration; Bioinformatics

Cite and Share

Yi Hu,Xiaomei Huang,Xiaohui Lu,Shan Lin. COL12A1 as a prognostic biomarker in HER2-enriched breast cancer and its association with immune infiltration. European Journal of Gynaecological Oncology. 2022. 43(5);85-90.


[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[2] Parker JS, Mullins M, Cheang MCU, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. Journal of Clinical Oncology. 2009; 27: 1160–1167.

[3] Dieci MV, Miglietta F, Griguolo G, Guarneri V. Biomarkers for HER2-positive metastatic breast cancer: beyond hormone receptors. Cancer Treatment Reviews. 2020; 88: 102064.

[4] Loi S, Sirtaine N, Piette F, Salgado R, Viale G, Van Eenoo F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. Journal of Clinical Oncology. 2013; 31: 860–867.

[5] Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, et al. Tumor infiltrating lymphocytes is prognostic and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Annals of Oncology. 2014; 25: 1544–1550.

[6] Wang L, Zhang X, Wang M, Li Y, Xu J, Wei J, et al. AMPD1 is associated with the immune response and serves as a prognostic marker in HER2-positive breast cancer. Frontiers in Oncology. 2021; 11: 749135.

[7] Pan TC, Zhang RZ, Mattei MG, Timpl R, Chu ML. Cloning and chromosomal location of human alpha 1(XVI) collagen. Proceedings of the National Academy of Sciences. 1992; 89: 6565–6569.

[8] Mohan V, Das A, Sagi I. Emerging roles of ECM remodeling processes in cancer. Seminars in Cancer Biology. 2020; 62: 192–200.

[9] Jiang X, Wu M, Xu X, Zhang L, Huang Y, Xu Z, et al. COL12A1, a novel potential prognostic factor and therapeutic target in gastric cancer. Molecular Medicine Reports. 2019; 20: 3103–3112.

[10] Wu Y, Xu Y. Integrated bioinformatics analysis of expression and gene regulation network of COL12A1 in colorectal cancer. Cancer Medicine. 2020; 9: 4743–4755.

[11] Ding J, Liu Y, Lai Y. Identifying MMP14 and COL12A1 as a potential combination of prognostic biomarkers in pancreatic ductal adenocarcinoma using integrated bioinformatics analysis. PeerJ. 2020; 8: e10419.

[12] Xu Y, Deng J, Wang L, Zhang H, Tang L, Huang Y, et al. Identification of candidate genes associated with breast cancer prognosis. DNA and Cell Biology. 2020; 39: 1205–1227.

[13] Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Research. 2017; 77: e108–e110.

[14] Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, et al. UALCAN: an update to the integrated cancer data analysis platform. Neoplasia. 2022; 25: 18–27.

[15] Lánczky A, Győrffy B. Web-based survival analysis tool tailored for medical research (KMplot): development and implementation. Journal of Medical Internet Research. 2021; 23: e27633.

[16] Munkacsy G, Santarpia L, Gyorffy B. Gene expression profiling in early breast cancer-patient stratification based on molecular and tumor microenvironment features. Biomedicines. 2022; 10: 248.

[17] Jia Q, Wang A, Yuan Y, Zhu B, Long H. Heterogeneity of the tumor immune microenvironment and its clinical relevance. Experimental Hematology & Oncology. 2022; 11: 24.

[18] Li Y, Su Z, Wei B, Qin M, Liang Z. Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis. Mathematical Biosciences and Engineering. 2021; 18: 5921–5942.

[19] Yearley JH, Gibson C, Yu N, Moon C, Murphy E, Juco J, et al. PD-L2 Expression in human tumors: relevance to anti-PD-1 therapy in cancer. Clinical Cancer Research. 2017; 23: 3158–3167.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time