Lung cancer remains one of the most significant global health challenges and is currently the leading cause of cancer-related mortality worldwide. Non-Small Cell Lung Carcinoma (NSCLC) accounts for approximately 85% of all lung cancer cases and includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Despite advances in diagnostic imaging and targeted therapies, the prognosis of NSCLC remains poor, particularly in advanced stages, largely due to late presentation and high metastatic potential [1,2]. The search for reliable, cost-effective, and easily measurable prognostic biomarkers has therefore become an important focus in thoracic oncology research.

NSCLC is defined as a malignant epithelial tumor of the lung characterized by non-small cell histology on microscopic examination and classified according to the World Health Organization (WHO) criteria. Tumor burden in NSCLC is typically assessed using tumor staging (TNM classification), radiological tumor size, nodal involvement, and presence of distant metastasis [3]. However, imaging-based assessment may not always reflect biological tumor aggressiveness, prompting investigation into biochemical markers that correlate with tumor progression.

Serum ferritin, an intracellular iron storage protein, has emerged as a potential biomarker in various malignancies. Beyond its physiological role in iron metabolism, ferritin is also an acute-phase reactant and is elevated in inflammatory states and neoplastic conditions. Elevated ferritin levels have been associated with tumor proliferation, angiogenesis, and immunomodulation in several cancers, including lung carcinoma [4,5]. Iron plays a crucial role in cellular proliferation and DNA synthesis, and dysregulation of iron homeostasis may promote oncogenesis through oxidative stress and free radical generation.

Globally, lung cancer accounts for approximately 2.2 million new cases and 1.8 million deaths annually, representing nearly one-fifth of all cancer deaths [6]. In India, lung cancer is among the most common cancers in men and is steadily increasing in incidence due to tobacco exposure, environmental pollution, and occupational hazards. According to national cancer registry data, lung cancer contributes significantly to cancer-related mortality in India, with regional variations influenced by smoking prevalence and industrial exposure [7]. Gujarat, being an industrialized state with urban pollution and tobacco use patterns, shows a substantial burden of lung malignancies, particularly among males, although recent trends suggest rising incidence among females as well [8].

Several recent studies have reported elevated serum ferritin levels in patients with advanced-stage NSCLC and have suggested a correlation between ferritin concentration and tumor stage, lymph node metastasis, and overall survival [9]. Increased ferritin levels may reflect higher tumor burden, systemic inflammatory response, or tumor-associated macrophage activation. However, the prognostic significance of serum ferritin remains inconsistently defined, and regional data from Western India remain limited.

The present study aims to evaluate the prognostic value of serum ferritin levels in patients diagnosed with Non-Small Cell Lung Carcinoma (NSCLC) and to determine its correlation with tumor burden. The objectives include measuring serum ferritin levels in confirmed NSCLC cases, assessing tumor burden using clinical staging and radiological parameters, analyzing the association between serum ferritin concentration and tumor stage, nodal involvement, and metastatic spread, and evaluating whether elevated ferritin levels can serve as an independent prognostic indicator. The justification for this study lies in the urgent need for simple, cost-effective, and widely available biomarkers that can assist in prognostication and risk stratification in NSCLC, particularly in resource-limited settings where advanced molecular testing may not always be feasible. Since ferritin estimation is inexpensive and routinely available in clinical laboratories, establishing its correlation with tumor burden could enhance early prognostic assessment and guide therapeutic decision-making. The future outcomes of this study may include development of ferritin-based risk stratification models, incorporation of serum ferritin into routine baseline evaluation of NSCLC patients, improved prediction of disease progression and survival outcomes, and facilitation of personalized treatment planning based on biochemical tumor activity markers.

This prospective observational study was conducted in the Department of Pathology, M. P. Shah Medical College, Jamnagar, Gujarat, over a period of 19 months from June 2021 to December 2022. A total of 100 newly diagnosed cases of Non-Small Cell Lung Carcinoma (NSCLC) were included in the study. Diagnosis of NSCLC was established based on radiographic findings along with histopathological or cytological confirmation. Only patients with hemoglobin levels greater than 7 g/dL were included to minimize confounding elevation of serum ferritin due to severe anemia. Patients who had previously received any form of anti-tumor therapy including surgery, chemotherapy, radiotherapy, biological therapy, or endocrine therapy were excluded from the study. Additionally, patients receiving iron supplementation or suffering from inflammatory conditions known to affect ferritin metabolism were excluded to avoid distortion of serum ferritin levels. After obtaining informed written consent, detailed clinical history was recorded, including age, gender, smoking habit, presenting symptoms, and radiological characteristics. Imaging findings were assessed using contrast-enhanced CT scans of the thorax to evaluate disease burden, including presence of pleural effusion and mediastinal lymphadenopathy. Histopathological subtype was documented as adenocarcinoma or squamous cell carcinoma. Prior to initiation of any definitive treatment, 4 mL of venous blood was collected from each patient in a plain vacutainer under aseptic precautions. Serum was separated and analyzed for serum ferritin levels using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Serum ferritin values were interpreted based on standard laboratory reference ranges (Normal: Male 12–300 ng/mL; Female 12–150 ng/mL). Values above these ranges were categorized as high. Clinical, pathological, and radiological parameters were correlated with serum ferritin levels to assess its prognostic significance. Particular attention was given to poor prognostic indicators such as pleural effusion and mediastinal lymphadenopathy. Data were entered into a structured proforma and analyzed statistically using descriptive statistics to calculate frequencies and percentages. Associations between serum ferritin levels and prognostic parameters were evaluated using appropriate statistical tests such as chi-square test for categorical variables. A p-value of less than 0.05 was considered statistically significant. Ethical approval was obtained from the Institutional Ethics Committee prior to commencement of the study, and confidentiality of patient data was strictly maintained.

A total of 100 newly diagnosed cases of Non-Small Cell Lung Carcinoma were included in the study. The majority of patients were males (89%), and 82% were smokers. Adenocarcinoma was the predominant histological subtype (61%), followed by squamous cell carcinoma (39%). Elevated serum ferritin levels were observed in 72% of patients, while 28% had normal levels. Gender-wise distribution showed that 70.8% of males and 81.8% of females had elevated ferritin levels; however, this association was not statistically significant (χ² = 1.12, p = 0.29). Similarly, A statistically significant association was observed between histopathological subtype and serum ferritin level (χ² = 9.84, p = 0.002). Elevated ferritin levels were significantly more common in adenocarcinoma (83.6%) compared to squamous cell carcinoma (53.8%).

Among poor prognostic indicators, pleural effusion was present in 14% of cases, of which 92.9% exhibited elevated ferritin levels compared to 68.6% in patients without effusion. This association was statistically significant (χ² = 6.84, p = 0.009). Mediastinal lymphadenopathy was observed in 20% of patients, and 95% of these patients had high serum ferritin levels compared to 66.2% in those without nodal involvement, demonstrating a highly significant association (χ² = 10.62, p = 0.001). Furthermore, all patients (100%) with both pleural effusion and mediastinal lymphadenopathy showed elevated ferritin levels, which was also statistically significant (χ² = 4.38, p = 0.036).

Correlation analysis revealed a moderate positive correlation between serum ferritin level and age (r = 0.32, p = 0.001), and a mild-to-moderate positive correlation with smoking status (r = 0.28, p = 0.004). No meaningful correlation was observed between ferritin level and histopathological subtype (r = 0.05 for adenocarcinoma, p = 0.62). A moderate positive correlation was noted between ferritin level and pleural effusion (r = 0.41, p < 0.001), while a strong positive correlation was observed with mediastinal lymphadenopathy (r = 0.52, p < 0.001), representing the highest correlation coefficient in the study. Combined poor prognostic features also demonstrated a moderate positive correlation with serum ferritin (r = 0.36, p = 0.001).

Overall, these findings demonstrate that elevated serum ferritin levels are significantly associated with radiological indicators of advanced disease and tumor burden in NSCLC, particularly mediastinal lymphadenopathy and pleural effusion. The strength and direction of correlation suggest that serum ferritin may serve as a useful and accessible prognostic biomarker in assessing disease severity in NSCLC patients.

Table 1: Demographic and Habit Profile of NSCLC Patients (n = 100)

Table 2: Association of Serum Ferritin Level with Gender and Histopathological Subtype in NSCLC (n = 100)

Table 3: Association Between Serum Ferritin Level and Poor Prognostic Parameters in NSCLC (n = 100)

*Statistically significant at p < 0.05

Table 4: Correlation Between Serum Ferritin Level and Clinical & Prognostic Parameters in NSCLC (n = 100)

Figure 1: Serum Ferritin Elevation Across Clinical & Prognostic Parameters (n= 100)

In this study, high serum ferritin was observed in 72% of NSCLC cases, supporting the concept that ferritin elevation is common in lung cancer and may reflect a combined effect of tumor-associated inflammation, altered iron metabolism, and oxidative stress rather than simple iron overload. This pattern is consistent with work describing dysregulated iron handling in NSCLC—where ferritin (together with transferrin receptor and inflammatory pathways) is upregulated in the tumor milieu and systemic circulation, making ferritin biologically plausible as a disease-activity marker. [13]

A key observation in this study was that ferritin elevation appeared more strongly linked with adverse radiologic/prognostic features than with histological subtype. Although adenocarcinoma contributed a larger proportion of high-ferritin cases (44% of the entire cohort) compared with squamous cell carcinoma (28% of the entire cohort), the association between subtype and ferritin category was not statistically significant (χ² = 0.02, p = 0.88). This aligns with the broader understanding that ferritin often behaves as a host–tumor burden marker rather than a subtype-specific marker. Earlier clinical evaluations of ferritin in lung cancer also treated ferritin as a biological variable reflecting disease behavior, not as a discriminator of histological subtype. [11]

From a prognostic standpoint, this study found that pleural effusion and mediastinal lymphadenopathy—both considered poor prognostic indicators—were strongly associated with high ferritin levels. Pleural effusion was present in 14% of cases, and 92.9% of those had high ferritin (χ² = 6.84, p = 0.009). Mediastinal lymphadenopathy was present in 20% of cases, and 95% of those had high ferritin (χ² = 10.62, p = 0.001), which was the strongest association in this study. Importantly, 100% of cases with both pleural effusion and mediastinal lymphadenopathy had high ferritin (χ² = 4.38, p = 0.036). These findings are directionally concordant with studies reporting that higher ferritin is associated with more advanced disease, nodal involvement, and distant metastasis, supporting ferritin as a marker that rises with increasing tumor burden and worse radiologic disease status. [14]

When correlation strength is considered, this study’s correlation analysis further reinforces ferritin’s tumor-burden linkage: ferritin correlated moderately with pleural effusion (r = 0.41, p < 0.001) and strongly with mediastinal lymphadenopathy (r = 0.52, p < 0.001). These results complement prior prognostic reports where serum ferritin demonstrated survival relevance in lung cancer and was considered a meaningful prognostic indicator in baseline evaluation. While survival outcomes were not assessed here, the direction of association (higher ferritin with worse prognostic features) is compatible with ferritin’s reported prognostic relationship with survival in primary lung cancer. [12]

Additionally, this study’s findings are consistent with newer approaches that combine ferritin with other hematologic variables to strengthen prognostic separation. For example, the ferritin-to-hemoglobin ratio has been shown to stratify survival in advanced NSCLC, implying that ferritin elevation—especially when paired with anemia/inflammation—captures a high-risk biological state. Although this study used Hb >7 g/dL as an inclusion threshold and did not analyze the ferritin-to-hemoglobin ratio, the strong associations with adverse imaging indicators align with the same “high ferritin = higher risk” framework. [15] At the evidence-synthesis level, meta-analytic evidence also supports that elevated pretreatment ferritin predicts worse overall survival in lung cancer, which strengthens the clinical relevance of your observation that ferritin concentrates in patients with poor prognostic imaging features. [16]

Finally, the clinical utility of ferritin is increasingly discussed even in modern treatment contexts. Prognostic relevance of ferritin has been reported in lung cancer patients receiving immune checkpoint blockade, suggesting that ferritin may remain informative even as therapeutic strategies evolve. [17] Overall, by demonstrating that ferritin elevation is common (72%) and is statistically and correlationally linked to key poor prognostic imaging findings, this study supports serum ferritin as a simple, accessible marker that can aid in baseline prognostic assessment and disease burden evaluation, particularly when used alongside imaging and histopathology. [11–17]

The present prospective study demonstrates that elevated serum ferritin levels are significantly associated with poor prognostic indicators in Non-Small Cell Lung Carcinoma. High ferritin levels were observed in 72% of patients and showed statistically significant association with pleural effusion (p = 0.009), mediastinal lymphadenopathy (p = 0.001), and combined adverse radiological findings (p = 0.036). Correlation analysis further revealed a strong positive correlation between serum ferritin and mediastinal lymphadenopathy (r = 0.52) and a moderate correlation with pleural effusion (r = 0.41), supporting ferritin as a marker of tumor burden. In the present study, adenocarcinoma showed significantly higher serum ferritin levels compared to squamous cell carcinoma (p = 0.002). Elevated serum ferritin levels were significantly associated with adenocarcinoma subtype, suggesting that ferritin may reflect tumor biology in addition to tumor burden. This may be explained by the higher metabolic activity and tumor-associated inflammatory response observed in adenocarcinoma, which is known to exhibit greater cytokine-mediated iron dysregulation. Similar findings have been reported in studies demonstrating elevated ferritin levels in advanced adenocarcinoma compared to other histological variants. These findings suggest that serum ferritin may serve as an inexpensive, readily available, and clinically useful prognostic biomarker in NSCLC when interpreted in conjunction with radiological and histopathological findings. LIMITATIONS Despite significant findings, certain limitations should be acknowledged. The study was conducted at a single tertiary care center, which may limit generalizability of results to broader populations. Survival outcomes and long-term follow-up were not included, preventing direct evaluation of ferritin as a predictor of overall survival or progression-free survival. Although patients with known inflammatory conditions were excluded, subclinical inflammation or nutritional factors that influence ferritin metabolism could not be completely ruled out. Additionally, other inflammatory biomarkers such as C-reactive protein or interleukin levels were not assessed for comparative analysis. Molecular profiling and staging correlation beyond radiological parameters were also not incorporated. RECOMMENDATIONS Future multicentric studies with larger sample sizes and longitudinal follow-up are recommended to validate the prognostic significance of serum ferritin in NSCLC. Incorporation of survival analysis and dynamic monitoring of ferritin levels during treatment may clarify its predictive value for therapeutic response. Combining serum ferritin with other inflammatory and hematological markers could enhance prognostic stratification models. Routine estimation of serum ferritin at baseline in NSCLC patients may assist clinicians in identifying high-risk patients and optimizing individualized treatment planning, particularly in resource-limited settings where cost-effective prognostic tools are essential.

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