Wu P, Chen J, Ding J, Shi F, Wu H, Yang J. Determinants of psychological emotions in lung cancer patients and their correlations with tumor markers and inflammatory cytokines. World J Psychiatry 2026; 16(10): 122042 [DOI: 10.5498/wjp.122042]
Corresponding Author of This Article
Peng Wu, Lecturer, School of Medical Laboratory Technology, Xinyang Vocational and Technical College, No. 48 24th Street, Yangshan New District, Xinyang 464000, Henan Province, China. victorwumed@163.com
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Psychology
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Wu P, Chen J, Ding J, Shi F, Wu H, Yang J. Determinants of psychological emotions in lung cancer patients and their correlations with tumor markers and inflammatory cytokines. World J Psychiatry 2026; 16(10): 122042 [DOI: 10.5498/wjp.122042]
Author contributions: Wu P wrote the manuscript, performed data analysis and interpretation; Wu P and Wu H provided the study materials; Wu P and Yang J collected and assembled the data; Chen J, Ding J, and Shi F conceptualized and designed the study; Yang J provided administrative support; Wu P and Chen J contributed equally to this manuscript and are co-first authors. All authors participated in manuscript writing and approved the final manuscript.
AI contribution statement: The authors declare that no AI tools were used in the development or writing of this manuscript and take full responsibility for its integrity, accuracy, and originality.
Supported by Henan Provincial Science and Technology Research Project, No. 242102310491; Henan Provincial Higher Education Key Scientific Research Project Plan, No. 25B320029; and Xinyang Municipal Science and Technology Research Project, No. 20250083.
Institutional review board statement: This study was approved by the Ethic Committee of Affiliated Hospital of Xinyang Vocational and Technical College (Approval No. 2024-01-18).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: No additional data are available.
Corresponding author: Peng Wu, Lecturer, School of Medical Laboratory Technology, Xinyang Vocational and Technical College, No. 48 24th Street, Yangshan New District, Xinyang 464000, Henan Province, China. victorwumed@163.com
Received: April 30, 2026 Revised: June 28, 2026 Accepted: July 28, 2026 Published online: October 19, 2026 Processing time: 163 Days and 1.3 Hours
Abstract
BACKGROUND
Lung cancer patients experience significant psychological distress, yet the underlying determinants and their biological implications are not well understood. Chronic negative emotions may influence peripheral tumor markers (TMs) and inflammatory cytokines (ICKs) via neuroendocrine-immune pathways.
AIM
To investigate the determinants of psychological conditions in lung cancer patients and analyze their correlations with TMs and ICKs.
METHODS
A total of 128 advanced non-small cell lung cancer patients who received chemoradiotherapy between January 2023 and December 2025 participated in a questionnaire survey. Demographic and clinical data were collected using a basic data questionnaire, while depression and anxiety levels were assessed using the Self-Rating Depression Scale (SDS)/Self-Rating Anxiety Scale (SAS). Determinants associated with anxiety and depression were explored, and correlations between TMs, ICKs, and anxiety and depression scores were analyzed.
RESULTS
The cohort had mean scores of 48.84 ± 7.56 on the SAS and 50.20 ± 8.81 on the SDS, with anxiety observed in 43.7% and depressive symptoms in 39.8% of patients. Regression analysis indicated that age and a per capita monthly household income below 4000 yuan were risk factors for anxiety, while a university education or higher offered protective benefits. Divorced or widowed status, a per capita monthly household income below 4000 yuan, and solitary living were identified as risk factors for depression. Lung cancer patients with anxiety or depression exhibited statistically elevated levels of carcinoembryonic antigen, neuron-specific enolase, cytokeratin fragment antigen 21-1, interleukin-6, and tumor necrosis factor-α, compared to those without these emotional disturbances. In all patients, SAS and SDS scores showed positive correlations with carcinoembryonic antigen, neuron-specific enolase, cytokeratin fragment antigen 21-1, interleukin-6, and tumor necrosis factor-α levels.
CONCLUSION
A significant proportion of lung cancer patients experience anxiety and depression, with monthly household income serving as a related factor. Patients suffering from psychological distress show elevated serum levels of TMs and ICKs. Emphasis should be placed on the importance of social support for the physical and mental health of patients during clinical diagnosis and treatment.
Core Tip: This study assessed the prevalence of anxiety and depression, alongside associated psychosocial factors, in 128 patients with stage C advanced non-small cell lung cancer undergoing chemoradiotherapy. Additionally, it examined the cross-sectional relationships between these factors and serum tumor markers and pro-inflammatory cytokines. The findings demonstrate a significant correlation between psychological distress and socioeconomic factors; notably, elevated levels of emotional distress are linked to higher biomarker concentrations. This study highlights potential psychoneuroimmunological pathways involved in lung cancer progression and emphasizes the importance of integrating mental health screening into cancer treatment to enhance patients’ physical and mental well-being and improve biological outcomes.
Citation: Wu P, Chen J, Ding J, Shi F, Wu H, Yang J. Determinants of psychological emotions in lung cancer patients and their correlations with tumor markers and inflammatory cytokines. World J Psychiatry 2026; 16(10): 122042
Lung cancer is a highly prevalent and fatal malignancy globally, with non-small cell lung cancer (NSCLC) representing more than 80% of all lung cancer cases[1]. The complex etiology of NSCLC involves environmental factors, genetic predispositions, and chronic lung infections, complicating its pathogenesis[2,3]. The absence of specific early clinical symptoms often leads to late-stage diagnoses, resulting in unfavorable 5-year survival rates ranging from 10% to 15%[4]. Consequently, there is a heavy reliance on systemic therapies, including radiotherapy, chemotherapy, and targeted therapies, which frequently induce systemic side effects such as severe gastrointestinal symptoms, malnutrition, and persistent fatigue[5,6]. Within the biopsychosocial model, these distressing physical symptoms, combined with the financial burden of prolonged treatment and the social stigma associated with smoking, exacerbate chronic psychological stress and negative emotions in NSCLC patients, fundamentally impacting their treatment behaviors and overall quality of life.
Anxiety and depression, the most prevalent mood disorders among oncology patients, significantly contribute to mental health issues and impair treatment compliance and prognoses[7]. Statistical estimates indicate that the incidence of depression in lung cancer patients ranges from 12.4% to 65%[8], while the prevalence of anxiety disorders falls between 20.9% and 65%[9], making lung cancer patients the most affected population regarding psychological disorders among all cancer types. Furthermore, the standardized suicide mortality rate for lung cancer patients is the highest among cancer patients[10]. Numerous studies, both domestic and international, have focused on the anxiety and depression experienced by lung cancer patients and explored related factors[11]. Recent psychoneuroimmunological research has begun to elucidate the bidirectional interactions between central psychological stress and peripheral tumor biology to better understand the overall impact of these emotional disorders. Serum tumor markers (TMs) serve as well-established indicators of tumor burden and therapeutic response. Accumulating evidence suggests that chronic anxiety and depression can indirectly influence TM levels by altering the tumor microenvironment. Specifically, psychological stress activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, resulting in the systemic release of pro-inflammatory cytokines (ICKs)[12,13]. This prolonged inflammatory state not only exacerbates depressive symptoms through neuroinflammatory pathways but also promotes tumor proliferation and angiogenesis, potentially driving fluctuations in serum TM levels. However, the precise clinical correlations among patient-specific emotional profiles, systemic ICK levels, and TM expression remain poorly characterized. Most previous studies have examined psychological risk factors, systemic inflammation, or tumor progression in isolation, neglecting the interactions among these dimensions in NSCLC. This gap in the literature necessitates further exploration.
To address this gap, this study aims to systematically analyze the prevalence of anxiety and depression in NSCLC patients along with their independent determinants. Through a cross-sectional study, the research seeks to elucidate the associations between these psychological factors and serum TMs as well as ICKs, ultimately revealing potential psychoneuroimmunological pathways linking negative emotions to tumor biology.
MATERIALS AND METHODS
Research participants
A questionnaire survey was conducted on eligible patients with advanced NSCLC undergoing chemoradiotherapy at the Affiliated Hospital of Xinyang Vocational and Technical College between January 2023 and December 2025. Inclusion criteria comprised: (1) Age ≥ 18 years; (2) Primary diagnosis of stage III-IV NSCLC confirmed by pathological and imaging examinations; (3) Initial diagnosis and treatment with chemoradiotherapy at our hospital (4 courses); (4) Sufficient language communication ability, audio-visual function, and mental state to cooperate with clinical evaluations and examinations; and (5) Completeness and availability of clinical data for collection and analysis. Exclusion criteria included: (1) Worsening condition; (2) Concurrent surgery, immunotherapy, or other treatments; (3) Recent significant personal or family events affecting the patient's mood; (4) Past or family history of mental illness; (5) Difficulty cooperating with the study due to audio-visual impairments, alexithymia, or coexisting mental health issues; (6) Recent medication affecting mental states; (7) Severe speech disorders or advanced dementia hindering questionnaire completion; (8) Treatment for anxiety or depression within the past month; (9) Presence of additional malignant tumors; and (10) Incomplete clinical data. Based on these criteria, a total of 128 patients were included in the final analysis.
Investigation methods
Demographics: Patient demographic and clinical data were obtained from electronic medical records and a self-designed questionnaire. Information collected included gender, age, body mass index (BMI), marital status, education level, per capita monthly household income (PCHI), residence, and medical payment methods. Clinical information such as pathological type, tumor stage, metastasis status, and toxicity was also recorded.
Patients’ psychological status: Depression and anxiety assessments utilized the Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS). Each scale consists of 20 items, rated on a 4-point scale (1-4 points). The standard score was calculated by summing all item scores and multiplying by 1.25. According to Chinese norms, the cutoff values were defined as 53 for SDS and 50 for SAS. Symptom severity classifications are: SDS - 53-62 for mild depression, 63-72 for moderate depression, and > 72 for severe depression; SAS - 50-59 for mild anxiety, 60-69 for moderate anxiety, and > 69 for severe anxiety.
Serum TMs and ICKs: Biochemical test results obtained post-chemoradiotherapy included levels of TMs: Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen, neuron-specific enolase (NSE), pro-gastrin-releasing peptide, and cytokeratin fragment antigen 21-1 (CYFRA21-1). ICKs analyzed included C-reactive protein, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha.
Quality control and data processing
Members of our research group served as investigators for the questionnaire survey. Prior to the initiation of the survey, unified training was conducted for all investigators to clarify the survey’s purpose and significance, main research objectives, questionnaire completion guidelines, and related requirements. Following the face-to-face investigations, questionnaires were collected on-site, and their quality was promptly verified. Items that were overlooked were cross-verified with the research subjects and supplemented immediately, thereby enhancing the questionnaire’s effectiveness. Laboratory examination indices were gathered from medical records, with inspection results double-checked and entered by two researchers. Data were processed using Excel software with a double data entry approach. Upon completion, data were cross-checked to minimize input errors and ensure the authenticity and reliability of the findings.
Statistical analysis
Statistical analyses were performed using SPSS version 25.0. Measurement data, including SDS and SAS scores, were expressed as mean ± SDs. Group comparisons were conducted using ANOVA with Tukey post hoc testing, while independent sample t-tests were employed for between-group comparisons. Categorical variables were reported as n (%), with comparisons analyzed using the χ2 test. Anxiety-related and depression-related determinants were identified through logistic multivariate regression analysis, and Pearson correlation coefficients were calculated to assess the relationship between anxiety and depression and serum indices. A P-value of less than 0.05 indicated statistically significant differences.
RESULTS
Anxiety and depression scores of the study cohort
Among the 128 lung cancer patients, the average scores were 48.84 ± 7.56 for the SAS and 50.20 ± 8.81 for the SDS. The cut-off points were 50 for anxiety and 53 for depression. Within the cohort, 43.7% displayed anxiety symptoms, and 39.8% exhibited depressive symptoms. Detailed distributions of patients with varying anxiety and depression states are presented in Table 1.
Table 1 Comparison of patients’ anxiety and depression scores, mean ± SD.
Univariate analysis of clinical characteristics of patients with or without anxiety
Of the 128 participants, 56 showed anxiety symptoms. Univariate analysis revealed significant differences between anxious and non-anxious patients in terms of age, education level, residence, PCHI, tumor stage, and toxic side effects (P < 0.05). However, no significant differences were observed regarding gender, BMI, marital status, medical insurance type, living arrangement, or histopathological type (P > 0.05), as indicated in Table 2.
Table 2 Univariate analysis of clinical characteristics of patients with or without anxiety, mean ± SD.
The significant factors identified in the univariate analysis were incorporated as independent variables in multivariate logistic regression analysis, with anxiety status as the dependent variable (0 = non-anxiety, 1 = anxiety). The results indicated that age and a PCHI of less than 4000 yuan were risk factors for anxiety symptoms (P < 0.05), while having a university education or higher served as a protective factor, as detailed in Table 3.
Table 3 Determinants of anxiety in lung cancer patients.
Variable
β
SE
Wald
P value
HR
95%CI
Constant
-20.867
5.413
14.862
0.000
0.000
Age (continuous variable)
0.305
0.082
13.692
0.000
1.356
1.154-1.594
Education level
0 = junior high school or below
4.845
0.089
1 = university, technical secondary school, or high school
-0.480
0.541
0.786
0.375
0.619
0.214-1.787
2 = university or above
-1.231
0.564
4.757
0.029
0.292
0.097-0.883
Per capita monthly household income (yuan)
0 ≥ 6000
11.174
0.004
1 = 4000-6000
0.913
0.578
2.490
0.115
2.491
0.802-7.737
2 ≤ 4000
1.973
0.600
10.807
0.001
7.195
2.218-23.333
Residence (0 = urban, 1 = rural)
0.577
0.450
1.646
0.200
1.781
0.737-4.302
Tumor staging (0 = III, 1 = IV)
0.586
0.459
1.628
0.202
1.797
0.730-4.423
Toxic and side effect (0 = grades 0-2, 1 = grades 3-4)
Univariate analysis of clinical characteristics of depression vs non-depression patients
Among the 128 patients, 51 exhibited depressive symptoms. Initial univariate screening revealed significant differences in marital status, PCHI, and living arrangement between patients with and without depression (P < 0.05). No significant differences were found regarding gender, age, BMI, education level, residence, medical insurance type, histopathological type, tumor stage, or toxic side effects (P > 0.05), as shown in Table 4.
Table 4 Univariate analysis of clinical characteristics of patients with depression or not, mean ± SD.
Analysis of influencing factors of depressive symptoms
Factors demonstrating significant differences in the single-factor comparison of depression among the 128 patients were used as independent variables in multivariate logistic regression analysis, with depression status as the dependent variable (0 = non-depression, 1 = depression). The results identified divorce or widowhood, a PCHI of less than 4000 yuan, and solitary living as risk factors for depression (Table 5).
Table 5 Analysis of depression-associated determinants in lung cancer patients.
Variable
β
SE
Wald
P value
HR
95%CI
Constant
-2.556
0.569
20.163
0.000
0.078
Marital status
0 = single
5.849
0.054
1 = married
0.811
0.547
2.200
0.138
2.251
0.771-6.577
2 = divorced or widowed
1.099
0.474
5.371
0.020
3.001
1.185-7.599
Per capita monthly household income (yuan)
7.810
0.020
0 ≥ 6000
1 = 4000-6000
0.966
0.555
3.033
0.082
2.627
0.886-7.793
2 ≤ 4000
1.598
0.572
7.789
0.005
4.941
1.609-15.174
Living arrangement (0 = shared living, 1 = solitary living)
Comparison of serum TMs indicated significantly elevated levels of CEA, NSE, and CYFRA21-1 in patients experiencing anxiety or depression compared to their counterparts (P < 0.05), while no significant differences were detected for squamous cell carcinoma antigen and pro-gastrin-releasing peptide (Table 6).
Table 6 Comparison of tumor marker levels, mean ± SD.
Analysis of ICK levels revealed notable increases in IL-6 and TNF-α between the anxiety vs non-anxiety groups and the depression vs non-depression groups, while C-reactive protein levels were comparable across the cohorts (Table 7).
Table 7 Levels of inflammatory cytokines, mean ± SD.
Correlation of anxiety and depression scores with various indexes
Pearson correlation analysis indicated a significant positive correlation between SAS and SDS scores and the levels of CEA, NSE, CYFRA21-1, IL-6, and TNF-α among all lung cancer patients (P < 0.05; Table 8).
Table 8 Correlation of Self-Rating Anxiety Scale and Self-Rating Depression Scale scores with marker levels.
As the global economy continues to grow, increasing attention is being directed toward mental health, particularly its relationship with cancer. Lung cancer is the leading cause of malignancy-related mortality worldwide. Consequently, the mental and psychological disorders experienced by lung cancer patients are receiving heightened scrutiny from researchers. Evidence has firmly established a correlation between anxiety and depression in lung cancer patients and reduced treatment compliance, diminished quality of life, and decreased survival rates[14]. For lung cancer patients experiencing comorbid anxiety and/or depression, timely mental health interventions and support may be crucial for improving clinical outcomes and enhancing overall quality of life. Therefore, this study explored the primary contributors to depression and anxiety in lung cancer patients by examining their clinical and demographic characteristics.
In our cohort of 128 lung cancer cases, 43.7% exhibited symptoms of anxiety, and 39.8% showed signs of depression. Regression analysis indicated that advancing age and a PCHI of less than 4000 yuan were significant risk factors for anxiety symptoms, whereas an educational background of university level or higher served as a protective factor. However, some studies suggest that age alone may not be an independent risk factor for anxiety in lung cancer patients[15]. Patients across different age brackets may display varying anxiety characteristics; for example, older patients might experience “silent anxiety” stemming from declines in physical function, solitary living, or fears of mortality[16]. A low PCHI is a major contributor to anxiety among lung cancer patients. Financial strain can exacerbate worries regarding treatment costs, familial responsibilities, and future uncertainties, thereby increasing anxiety risk[17]. Numerous studies and clinical observations support this conclusion[18,19]. Given that lung cancer treatment often involves a protracted process - incorporating surgery, chemotherapy, targeted therapy, or immunotherapy - some of which may not be fully covered by medical insurance or have low reimbursement ratios, the financial burden can lead to substantial out-of-pocket expenses. Patients with lower PCHI may find it increasingly difficult to sustain ongoing treatment, leading to choices of suboptimal treatment options or even interruptions in care, which in turn heighten anxiety levels. Additionally, possessing a university education or higher correlates with reduced anxiety in lung cancer patients. Existing research indicates that higher education significantly lowers anxiety risk by enhancing health literacy, improving coping mechanisms, optimizing behavioral patterns, and facilitating access to social resources[20,21]. Educated patients often comprehend their diagnosis, treatment plans, and prognostic information more effectively, which mitigates catastrophic thinking about the unknown and lessens anxiety. When examining determinants associated with depression, divorce or widowhood, a PCHI of less than 4000 yuan, and solitary living were identified as significant risk factors. The relationship between marital status and social support levels is well-documented; major life events such as divorce or widowhood markedly weaken a patient’s psychological support system, increasing feelings of loneliness and helplessness, which subsequently elevate the risk of developing depression[22,23]. A longitudinal population-based study involving 33184 adults aged 45 years and older found that widowhood or divorce significantly increased the risk of depression and anxiety (odds ratio = 1.82, 95% confidence interval: 1.65-2.01); this effect was particularly pronounced among cancer patients, suggesting that breakdowns in social support are a core mechanism underlying psychological burdens[24]. Furthermore, experiences of widowhood or divorce are frequently accompanied by living alone. Numerous studies consistently demonstrate that solitary living significantly heightens depression risk in lung cancer patients by exacerbating feelings of loneliness, diminishing social support, and reducing caregiving resources, with this impact being particularly notable among elderly patients and those lacking family support.
Finally, an analysis of serum TM and ICK levels was conducted. Patients with anxiety or depression exhibited significantly elevated levels of CEA, NSE, CYFRA21-1, IL-6, and TNF-α compared to their counterparts without these psychological conditions. Additionally, scores from the SAS and SDS were positively correlated with concentrations of CEA, NSE, CYFRA21-1, IL-6, and TNF-α across all patients. These findings suggest that anxiety and depression may influence serum TM levels in lung cancer cases. Chronic anxiety or depression can activate the hypothalamic-pituitary-adrenal axis, resulting in sustained glucocorticoid secretion, which contributes to chronic low-grade inflammation[25,26]. Elevated serum levels of pro-ICKs, such as IL-6 and TNF-α, have been associated with patients experiencing depression, potentially promoting tumor cell proliferation and indirectly affecting TM expression (e.g., CEA, CYFRA21-1). In NSCLC patients, CYFRA21-1 levels are reported to be 15%-25% higher and fluctuate more in individuals who have undergone significant psychological trauma or suffered long-term depression, compared to those who are emotionally stable[27]. Mood fluctuations can trigger sympathetic nerve excitation, resulting in bronchial contraction and stress-induced damage to alveolar epithelial cells. An increase in lung tissue cell damage leads to the release of CYFRA21-1, which is normally present in the alveolar epithelium, into the bloodstream, thereby raising its detectable levels[28]. NSE, primarily found in neurons and neuroendocrine cells, may also rise due to chronic anxiety and depression. Prolonged sympathetic nerve activation under these conditions results in large quantities of catecholamine hormones being secreted, which can metabolically stimulate neuroendocrine cells, leading to increased NSE release[29]. Consequently, fluctuations in emotional states may result in false elevations of TMs.
This study has several limitations. First, the design makes it difficult to definitively establish a causal relationship between psychological distress and changes in serum TMs or ICKs. Second, as the study was limited to a single center with a relatively small sample size, the generalizability of the findings to a larger population of lung cancer patients may be restricted. Third, while key psychosocial factors were analyzed, potential confounding variables such as the baseline burden of physical symptoms, systemic treatment toxicity, and nutritional status were not adequately controlled for and may independently influence mood and biomarkers. Finally, the assessment of anxiety and depression relied solely on self-report scales (SAS/SDS) rather than structured clinical diagnostic interviews, potentially introducing reporting bias. Therefore, prospective, large-scale multicenter studies are needed to validate these longitudinal trajectories and further elucidate the precise mechanistic pathways linking psychological distress to objective tumor biology in lung cancer patients.
CONCLUSION
In conclusion, lung cancer patients are likely to experience anxiety and depression as their condition or treatment progresses. Clinicians should be cognizant of the impact of adverse moods such as anxiety and depression on patients’ physiological states during lung cancer diagnosis and treatment. Providing timely counseling to support mental health is essential to facilitate treatment adherence and optimize therapeutic outcomes.
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