Exploration of Immunology

Table 2. Stage-specific immunoglobulin (IG) proteins identified across CRC progression.

Component	Proteins
	Early stages			Advanced stages
	Stage I		Stage II	Stage III	Stage IV
Sequence	MAWTPLFLFLLTCCPGSNSQTVVTQEPSLTVSPGGTVTLTCASSTGAVTSGYYPNWFQQKPGQAPRALIYSTSNKHSWTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLYYGGAQ	MAWAPLLLTLLSLLTGSLSQPVLTQPPSASASLGASVTLTCTLSSGYSNYKVDWYQQRPGKGPRFVMRVGTGGIVGSKGDGIPDRFSVLGSGLNRYLTIKNIQEEDESDYHCGADHGSGSNFV	MDLMCKKMKHLWFFLLLVAAPRWVLSQLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR	MMEFGLSWVFLVAIFKGVQCEVQLVESGEGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEYVSAISSNGGSTYYADSVKGRFTISRDNSKNTLYLQMGSLRAEDMAVYYCAR	MEFGLSWLFLVAILKGVQCEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
No. of AA	117	123	125	118	117
Formula	C₅₆₀H₈₄₇N₁₄₁O₁₇₁S₅	C₅₇₅H₉₀₃N₁₅₇O₁₈₀S₄	C₆₃₄H₉₇₉N₁₅₉O₁₈₁S₆	C₅₇₃H₈₈₀N₁₅₂O₁₇₁S₈	C₅₆₁H₈₆₈N₁₄₈O₁₆₉S₆
Molecular weight (mol.wt)	12,451.03	13,023.68	13,917.06	12,890.69	12,582.31
IIx/stability	32.73/stable	21.31/stable	39.81/stable	37.58/stable	39.20/stable
Uniprot accession, protein & gene ID	P04211, IG lambda variable 7-43 (IGLV7-43)	A0A0B4J1Y8 (IGLV9-49)	P01824, IG heavy variable 4-39 (IGHV4-39)	A0A075B6Q5 ( IGHV3-64)	P01764 (IGHV3-23)
Structure
Functions	-Prognostic biomarker in esophageal squamous cell carcinoma (ESCC) -Involved in immune tolerance and suppression	-Participates in antigen recognition -Triggers clonal expansion and differentiation of B lymphocytes; mediates effector phase of humoral immunity -Facilitates antigen-based affinity maturation	-Implicated in aggressive forms of chronic lymphocytic leukemia (CLL) -Strongly associated with Richter transformation -Exhibits polyreactive antigen binding; cooperates with NOTCH1 mutations and trisomy 12 -Driver of disease aggressiveness and transformation	-Prognostic biomarker in head and neck squamous cell carcinoma (HNSCC) -Contributes to B cell malignancy pathogenesis [e.g., Waldenström’s macroglobulinemia (WM), IgM monoclonal gammopathy of undetermined significance (IgM-MGUS)]	-Interacts with defensin alpha 3 (DEFA3) via SNPs; involved in gene regulation in CLL -Serves as a scaffold for PD-1-blocking antibodies -Linked to site-specific genetic mutations in mucosa-associated lymphoid tissue (MALT) lymphoma -Defines a distinct subtype in splenic lymphomas -Highly frequent and mostly mutated; essential for B cell clone development in WM

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This table summarizes representative IG variable region proteins identified by electrospray ionization nano-liquid chromatography tandem mass spectrometry (ESI-nanoLC-MS/MS) in plasma samples from patients with early-stage (stages I–II) and advanced-stage (stages III–IV) CRC. For each IG, the amino acid (AA) sequence, length, molecular formula, mol.wt, instability index (IIx), UniProt accession number, protein and gene identifiers, and reported biological functions are shown. Stage-specific classification was based on Venn diagram analysis, where proteins were uniquely detected in a single CRC stage and absent in other stages. These IGs were subsequently prioritized for stability assessment and downstream computational analyses.

Supplementary materials

Other supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/1003252_sup_1.pdf.

Declarations

Acknowledgments

We would like to thank Mrs. J.S.Sakkthi Prabha for formatting and proofreading the manuscript.

Author contributions

RA: Conceptualization, Investigation, Methodology, Writing—original draft. VB, SK, JR, and RS: Writing—review & editing, Funding acquisition, Resources. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Ethical approval

The study was approved by the AVMC Institutional Human Ethics Committee (IHEC) under protocol No. AVMC-2021-04-14. The study was conducted in accordance with the principles of the Declaration of Helsinki (2024 revision).

Consent to participate

Written informed consent was obtained from all participants prior to sample collection.

Consent to publication

Not applicable.

Availability of data and materials

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

Funding

Seed funding support to conduct this research (VMRF/Research/Seed Money/30th April, 2021) was provided by VMRF. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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